RGD-mimic polyamidoamine-montmorillonite composites with tunable stiffness as scaffolds for bone tissue-engineering applications

This paper reports on the development of montmorillonite (MMT)-reinforced hydrogels, based on a peptidomimetic polyamidoamine carrying guanidine pendants (AGMA1), as substrates for the osteo-induction of osteoblast precursor cells. AGMA1 hydrogels of various degrees of crosslinking responded favourably to MMT reinforcement, giving rise to composite hydrogels with shear storage modulus G', when fully swollen in water, up to 200 kPa, i.e. 20 times higher than the virgin hydrogels and of the same order or higher than other hydrogel-based composites proposed for orthopaedic applications. This significant improvement was ascribed to the effective interpenetration between the polymer matrix and t…

Core-Shell Arginine-Containing Chitosan Microparticles for Enhanced Transcorneal Permeation of Drugs

Chitosan oligosaccharide (C) was functionalized with L-arginine (A) and short hydrocarbon chains (C-8) to design an amphiphilic copolymer, henceforth CAC(8), leading to microparticles (MPs) consisting of an arginine-decorated hydrophilic shell and inner hydrophobic domains allowing the encapsulation of high amount hydrophobic drugs such as sorafenib tosylate (>10% w/w). L-arginine side chains were selected in order to impart the final MPs enhanced transcorneal penetration properties, thus overcoming the typical biological barriers which hamper the absorption of drugs upon topical ocular administration. The mucoadhesive properties and drug release profile of the CAC(8) MPs (CAC(8)-MPs) were …

Fluorescent Boron Oxide Nanodisks as Biocompatible Multi-messenger Sensors for Ultrasensitive Ni$^{2+}$ Detection

Boron-based nanocomposites are very promising for a wide range of technological applications, spanning from microelectronics to nanomedicine. A large variety of B-based nanomaterials has been already observed, such as borospherene, B nanotubes and nanoparticles, and boron nitride nanoparticles. However, their fabrication usually involves toxic precursors or leads to very low yields or small boron atom concentration. In this work, we report the synthesis of nanometric B$_{2}$O$_{3}$ nanodisks, a family of nanomaterials with a quasi-2D morphology capable of intense fluorescence in the visible range. Such as boron-based nanomaterial, which we synthesized by pulsed laser ablation of a boron tar…

Disclosing the emissive surface traps in green-emitting carbon nanodots

Abstract The bright photoluminescence of surface-functionalized carbon nanoparticles, known as carbon nanodots (CDs), has been studied for more than a decade because of its fundamental photo-physical interest and strong technological potential. However, the essential nature of the electronic states involved in their typical light emission remains very elusive. Here, we provide conclusive evidence that surface carboxylic moieties are the key to CD fluorescence. The synergy of nanosecond and femtosecond optical studies, cryogenic fluorescence, computational investigations and chemical engineering of a strategically chosen model CD system, allows to demonstrate that their visible-light transit…

Carbon Nanodots as Functional Excipient to Develop Highly Stable and Smart PLGA Nanoparticles Useful in Cancer Theranostics

Theranostic systems have attracted considerable attention for their multifunctional approach to cancer. Among these, carbon nanodots (CDs) emerged as luminescent nanomaterials due to their exceptional chemical properties, synthetic ease, biocompatibility, and for their photothermal and fluorescent properties useful in cancer photothermal therapy. However, premature renal excretion due to the small size of these particles limits their biomedical application. To overcome these limitations, here, hybrid poly(lactic-co-glycolic acid) (PLGA-CDs) nanoparticles with suitable size distribution and stability have been developed. CDs were decisive in the preparation of polymeric nanoparticles, not on…

A soluble biocompatible guanidine-containing polyamidoamine as promoter of primary brain cell adhesion andin vitrocell culturing

This paper reports on a novel application of an amphoteric water-soluble polyamidoamine named AGMA1 bearing 4-butylguanidine pendants. AGMA1 is an amphoteric, prevailingly cationic polyelectrolyte with isoelectric point of about 10. At pH 7.4 it is zwitterionic with an average of 0.55 excess positive charges per unit, notwithstanding it is highly biocompatible. In this work, it was found that AGMA1 surface-adsorbed on cell culturing coverslips exhibits excellent properties as adhesion and proliferation promoter of primary brain cells such as microglia, as well as of hippocampal neurons and astrocytes. Microglia cells cultured on AGMA1-coated coverslips substrate displayed the typical restin…

Preparation and Characterization of Inulin Coated Gold Nanoparticles for Selective Delivery of Doxorubicin to Breast Cancer Cells

A novel folate-targeted gold-based nanosystem for achieving selectivity towards folate receptor FR positive cells is proposed, by virtue of the fact that the FR is a molecularly targeted entity overexpressed in a wide spectrum of solid tumors. A new inulin-folate derivative INU-FA has been synthesized to act as coating agent for 40 nm gold nanoparticles. The obtained polymer-coated gold nanoparticles [email protected] were characterized in terms of hydrodynamic radius, shape, zeta potential, and aqueous stability and were loaded with doxorubicin [email protected]/Doxo. Its release capability was tested in different release media. The selectivity of [email protected]/Doxo system towards FRs-…

Inulin-Ethylenediamine Coated SPIONs Magnetoplexes: A Promising Tool for Improving siRNA Delivery.

An inulin based polycation (Inu-EDA) has been synthesized by the grafting of ethylenediamine molecules onto inulin backbone. The obtained inulin copolymer has been though to coat SPIONs (IC-SPIONs) and obtain stable magnetoplexes by complexation of IC-SPIONs with a model duplexed siRNA, for improving oligonucleotide transfection efficiency.The physical-chemical characteristics of IC-SPIONs and IC-SPIONs/siRNA magnetoplexes have been investigated by scanning and transmission electron microscopies, dynamic light scattering, FT-IR and qualitative surface elementary analysis. Cell compatibility and internalization in vitro of IC-SPIONs have been evaluated by MTS and fluorescence microscopy resp…

Mucus and Cell-Penetrating Nanoparticles Embedded in Nano-into-Micro Formulations for Pulmonary Delivery of Ivacaftor in Patients with Cystic Fibrosis

Here, mucus-penetrating nanoparticles (NPs) for pulmonary administration of ivacaftor in patients with cystic fibrosis (CF) were produced with the dual aim of enhancing ivacaftor delivery to the airway epithelial cells, by rapid diffusion through the mucus barrier, and at the same time, promoting ivacaftor lung cellular uptake. Pegylated and Tat-decorated fluorescent nanoparticles (FNPs) were produced by nanoprecipitation, starting from two synthetic copolymers, and showed nanometric sizes (∼70 nm), a slightly negative ζ potential, and high cytocompatibility toward human bronchial epithelium cells. After having showed the significant presence of poly(ethylene glycol) chains and Tat protein …

Biotin-Containing Reduced Graphene Oxide-Based Nanosystem as a Multieffect Anticancer Agent: Combining Hyperthermia with Targeted Chemotherapy

Among the relevant properties of graphene derivatives, their ability of acting as an energy-converting device so as to produce heat (i.e., thermoablation and hyperthermia) was more recently taken into account for the treatment of solid tumors. In this pioneering study, for the first time, the in vitro RGO-induced hyperthermia was assessed and combined with the stimuli-sensitive anticancer effect of a biotinylated inulin-doxorubicin conjugate (CJ-PEGBT), hence, getting to a nanosystem endowed with synergic anticancer effects and high specificity. CJ-PEGBT was synthesized by linking pentynoic acid and citraconic acid to inulin. The citraconylamide pendants, used as pH reversible spacer, were …

Photocycle of Excitons in Nitrogen-Rich Carbon Nanodots: Implications for Photocatalysis and Photovoltaics

Nitrogen-rich carbon nanodots have emerged as promising nanomaterials for a wide range of applications where a highly emissive and photoactive material with low toxicity and cost-effectiveness is required. One of their hallmarks is indeed a bright, tunable fluorescence of excitonic nature. Disentangling the origin of their optical absorption and fluorescence properties and uncovering relaxation channels and interactions with solvents are some of the most debated issues in the field. Uncovering these aspects is essential for targeted applications, especially in the fields of photocatalysis but also photovoltaics and optoelectronics. Here, we present dedicated transient absorption measurement…

Disentangling size effects and spectral inhomogeneity in carbon nanodots by ultrafast dynamical hole-burning.

Carbon nanodots (CDs) are a novel family of nanomaterials exhibiting unique optical properties. In particular, their bright and tunable fluorescence redefines the paradigm of carbon as a "black" material and is considered very appealing for many applications. While the field keeps growing, understanding CDs fundamental properties and relating them to their variable structures becomes more and more critical. Two crucial problems concern the effect of size on the electronic structure of CDs, and to what extent their optical properties are influenced by structural disorder. Furthermore, it remains largely unclear whether traditional concepts borrowed from the photo-physics of semiconductor qua…

Linear biocompatible mannosylated PAAs as potential broad-­‐spectrum microbicides for sexually transmitted diseases

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Synthesis of Biocompatible and Biodegradable Polyamidoamines Microgels via a Simple and Reliable Statistical Approach.

Polyamidoamines (PAAs) are biocompatible and biodegradable polymers with a huge potential as biomaterials for pharmaceutical applications. They are obtained by the step-wise aza-Michael polyaddition of bifunctional or multifunctional amines with bisacrylamides in water. To the best of our knowledge, no synthetic protocols leading to hyperbranched PAAs as well as PAA microgels have been published so far. To fill this gap, a statistical approach was established in this work to fine-tune the aza-Michael polyaddition stoichiometry when a multifunctional co-monomer (bf) is added to a mixture of bifunctional monomers with complementary functions (a2 + b2), possibly even in presence of a monofunct…

Linear biocompatible glyco-polyamidoamines as dual action mode virus infection inhibitors with potential as broad-spectrum microbicides for sexually transmitted diseases

AbstractThe initial steps of viral infections are mediated by interactions between viral proteins and cellular receptors. Blocking the latter with high-affinity ligands may inhibit infection. DC-SIGN, a C-type lectin receptor expressed by immature dendritic cells and macrophages, mediates human immunodeficiency virus (HIV) infection by recognizing mannose clusters on the HIV-1 gp120 envelope glycoprotein. Mannosylated glycodendrimers act as HIV entry inhibitors thanks to their ability to block this receptor. Previously, an amphoteric, but prevailingly cationic polyamidoamine named AGMA1 proved effective as infection inhibitor for several heparan sulfate proteoglycan-dependent viruses, such …

Double-Network-Structured Graphene Oxide-Containing Nanogels as Photothermal Agents for the Treatment of Colorectal Cancer.

Here, we reported the production of hyaluronic acid/polyaspartamide-based double-network nanogels for the potential treatment of colorectal carcinoma. Graphene oxide, thanks to the huge aromatic surface area, allows to easily load high amount of irinotecan (33.0% w/w) and confers to the system hyperthermic properties when irradiated with a near-infrared (NIR) laser beam. We demonstrate that the release of antitumor drug is influenced both by the pH of the external medium and the NIR irradiation process. In vitro biological studies, conducted on human colon cancer cells (HCT 116), revealed that nanogels are uptaken by the cancer cells and, in the presence of the antitumor drug, can produce a…

Design of New Polyaspartamide Copolymers for siRNA Delivery in Antiasthmatic Therapy

Here, a novel protonable copolymer was realized for the production of polyplexes with a siRNA (inhibitor of STAT6 expression in asthma), with the aim of a pulmonary administration. The polycation was synthesized by derivatization of &alpha

PHEA-Dox nanoparticles as pH-sensitive model for drug delivery in tumour treatment.

PHEA-Dox nanoparticles as pH-sensitive model for drug delivery in tumour treatment. S. Camporaa, G. Adamoa, N. Maurob, C. Scialabbab, M. Licciardib, G. Giammonab and G. Ghersia. aDipartmento di “Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche” (STEBICEF), Università di Palermo, Viale delle Scienze Ed. 16, 90128 Palermo, Italy. bLaboratory of Biocompatible Polymers, Dipartmento di “Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche” (STEBICEF), Università di Palermo, Via Archirafi, 32 90123 Palermo, Italy. Classical chemotherapeutic applications, using molecules such as doxorubicin (Dox), have side effects due to an unspecific action. In order to obtain a specific release of…

Carbon Nanodots for On Demand Chemophotothermal Therapy Combination to Elicit Necroptosis: Overcoming Apoptosis Resistance in Breast Cancer Cell Lines

Background: Engineered luminescent carbon nanodots (CDs) are appealing nanomaterials for cancer image-guided photothermal therapy combining near infrared (NIR)&ndash

Eight-week consumption of milk enriched with omega 3 fatty acids raises their blood concentrations yet does not affect lipids and cardiovascular disease risk factors in adult healthy volunteers

Adequate concentrations of omega 3 fatty acids (FA) may be maintained by consuming foods naturally rich in or functional foods enriched with those essential FA. We assessed the effects of an 8-week consumption of milk enriched with 400. mg of omega 3 FA on blood lipid levels and selected cardiovascular risk factors in adult healthy volunteers. Participants (n= 157) were randomized to consume - for eight weeks - either 500. mL/day of 1% fat milk providing 150. mg of eicosapentaenoic (EPA), 150. mg of docosahexaenoic (DHA), and 100. mg of α-linolenic (ALA) acids or 500. mL/day of non-enriched 1% fat milk. At week 8, we observed significant increments of blood EPA and DHA in the intervention g…

Inulin-based polymer coated SPIONs as potential drug delivery systems for targeted cancer therapy

This paper deal with the synthesis and characterization of PEGylated squalene-grafted-inulin amphiphile capable of self-assembling and self-organizing into nanocarriers once placed in aqueous media. It was exploited as coating agent for obtaining doxorubicin loaded superparamagnetic iron oxide nanoparticles (SPIONs) endowed with stealth like behavior and excellent physicochemical stability. Inulin was firstly modified in the side chain with primary amine groups, followed in turn by conjugation with squalenoyl derivatives through common amidic coupling agents and PEGylation by imine linkage. Polymer coated SPIONs were so obtained by spontaneous self-assembling of inulin copolymer onto magnet…

Polyaminoacid–doxorubicin prodrug micelles as highly selective therapeutics for targeted cancer therapy

An amphiphilic copolymer carrying high-dose doxorubicin (21% on a weight basis), PHEA–EDA–P,C–Doxo, was prepared by coupling doxorubicin with a biocompatible polyaminoacid through a pH-sensitive spacer. Additional derivatization with 4-pentynoic acid endows it with self-assembling properties by means of π–π stacking. These micelles can be triggered to promptly release drug in lysosomes (∼40% in 12 h) through pH-dependent micelle hydrolysis after uptake. In vitro tests on co-cultures of cancer (MDA-MB 231) and normal (HB-2) breast cells proved that the conjugate was selectively internalized into the former rather than normal cells, exploiting the caveolae-dependent endocytosis pathway, expla…

SPIONs embedded in polyamino acid nanogels to synergistically treat tumor microenvironment and breast cancer cells.

Abstract The extremely complex tumor microenvironment (TME) in humans is the major responsible for the therapeutic failure in cancer nanomedicine. A new concept of disease-driven nanomedicine, henceforth named “Theranomics”, which attempts to target cancer cells and TME on the whole, represents an attractive alternative. Herein, a nanomedicine able to co-deliver doxorubicin and a tumor suppressive proteolytic protein such as collagenase-2 was developed. We successfully obtained superparamagnetic nanogels (SPIONs/Doco@Col) via the intermolecular azide-alkyne Huisgen cycloaddition. We demonstrated that a local ECM degradation and remodeling in solid tumors by means of collagenase-2 could enha…

Understanding the role of graphene oxide in the capture and eradication of circulating tumor cells

The capture of circulating cancer cells on functional biomaterials is expected to control metastatic spread of a tumor, which is related to good probability containing the progression of disease burden. (1) The physicochemical characteristics of a biomaterial surface highly affect cell recruitment and adhesion, which is of great importance in such applications. Here, we designed a poly(caprolactone)-based nanocompsite scaffold, henceforth PCLMF-GO, to simultaneously recruit and kill circulating cancer cells by tuning physicochemical features of the scaffold surface through nitrogen plasma activation and hetero-phase graphene oxide (GO) covalent functionalization. Nitrogen plasma activation …

Self-organized environment-sensitive inulin–doxorubicin conjugate with a selective cytotoxic effect towards cancer cells

An inulin-based random copolymer bearing high dose doxorubicin (18.45% on a weight basis), INU-EDA-P, C-DOXO, was prepared by coupling doxorubicin with inulin though a citraconylamide bridge used as a pH sensitive spacer. A further conjugation with pentynoic acid via an amidic bond led to the hydrophobization of the copolymer which allows the acquisition of a self-assembling ability at low concentration (0.33 mg mL(-1)) combining both Pi-Pi stacking and London interactions. Drug release studies were carried out at different pH demonstrating a remarkable pH dependency, where the maximum release rate was observed at pH mimicking cancer tissue and lysosomal environments. Besides, by measuring …

Graphene oxide containing hyaluronic acid based nanogels for the potential treatment of colorectal cancer

Here, we reported the production of graphene oxide (GO) containing nanogels produced by a top-down procedure employing as a starting biomaterial an amino derivative of hyaluronic acid named HA-EDA. This derivative was reacted, in the presence of single layer GO, with α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide-((2-aminoethyl)-carbamate)-divinyl sulfone (PHEA-DVS) employed as a macromolecular crosslinking agent. The so obtained hydrogel was homogenized by ultra-turrax and high pressure homogenizer and nanogels with Z-average of 390 nm and PDI of 0.22 were obtained. These nanogels were employed to incorporate Irinotecan (IT), an antitumor drug used in the treatment of colorectal carcinoma. It …

Self-Ordering Secondary Structure of d- and l-Arginine-Derived Polyamidoamino Acids

This paper reports on synthesis, acid–base properties and pH-dependent structuring in water of d-, l- and d,l-ARGO7, bioinspired polymers obtained by polyaddition of the corresponding arginine stereoisomers with N,N′-methylenebis(acrylamide). The circular dichroism spectra of d- and l-ARGO7 showed a peak at 228 nm and quickly and reversibly responded to pH changes, but were nearly unaffected by temperature, ionic strength, and denaturating agents. Theoretical modeling studies of L-ARGO7 showed that it assumed a folded structure. Intramolecular interactions led to transoid arrangements of the main chain reminiscent of the protein hairpin motif. Torsion angles showed a quite similar distribut…

Galactosylated Polymer/Gold Nanorods Nanocomposites for Sustained and Pulsed Chemo-Photothermal Treatments of Hepatocarcinoma

In this paper, we propose a rational design of a hybrid nanosystem capable of locally delivering a high amount of hydrophobic anticancer drugs (sorafenib or lenvatinib) and heat (hyperthermia) in a remote-controlled manner. We combined in a unique nanosystem the excellent NIR photothermal conversion of gold nanorods (AuNRs) with the ability of a specially designed galactosylated amphiphilic graft copolymer (PHEA-g-BIB-pButMA-g-PEG-GAL) able to recognize hepatic cells overexpressing the asialoglycoprotein receptor (ASGPR) on their membranes, thus giving rise to a smart composite nanosystem for the NIR-triggered chemo-phototherapy of hepatocarcinoma. In order to allow the internalization of A…

Amphoteric polyamidoamines in the treatment of malaria

The present invention relates to the use of amphoteric polyamidoamines with MW of 10-100 kDa as antimalarial agents or carriers of antimalarial drugs and to formulations thereof.

Poly-l-Lactic Acid Nanofiber-Polyamidoamine Hydrogel Composites: Preparation, Properties, and Preliminary Evaluation as Scaffolds for Human Pluripotent Stem Cell Culturing.

Electrospun poly-l-lactic acid (PLLA) nanofiber mats carrying surface amine groups, previously introduced by nitrogen atmospheric pressure nonequilibrium plasma, are embedded into aqueous solutions of oligomeric acrylamide-end capped AGMA1, a biocompatible polyamidoamine with arg-gly-asp (RGD)-reminiscent repeating units. The resultant mixture is finally cured giving PLLA-AGMA1 hydrogel composites that absorb large amounts of water and, in the swollen state, are translucent, soft, and pliable, yet as strong as the parent PLLA mat. They do not split apart from each other when swollen in water and remain highly flexible and resistant, since the hydrogel portion is covalently grafted onto the …

Hetero-difunctional dimers as building blocks for the synthesis of poly(amidoamine)s with hetero-difunctional chain terminals and their derivatives

This article reports on a simple and straightforward preparation method of poly(amidoamine)s (PAAs) with hetero-difunctional chain ends as well as of several up to now hardly obtainable PAA derivatives of biotechnological interest, such as for instance PAAs of controlled molecular weight and narrow polydispersity mono-functionalized at one end with an acrylamide group, PAAs with star-like molecular architecture, graft-PAA-protein conjugates, “tadpole-like” PAA conjugates with hydrophobic moieties able to self assemble into nanoparticles in aqueous media. The key step was to design suitable building blocks consisting of hetero-difunctional dimers (HDDs). In particular, the HDDs considered we…

Branched High Molecular Weight Glycopolypeptide With Broad-Spectrum Antimicrobial Activity for the Treatment of Biofilm Related Infections.

There are few therapeutic options to simultaneously tackle Staphylococcus aureus and Pseudomonas aeruginosa, two of the most relevant nosocomial and antibiotic-resistant pathogens responsible for implant, catheters and wound severe infections. The design and synthesis of polymers with inherent antimicrobial activity have gained increasing attention as a safe strategy to treat multi-drug-resistant microbes. Here, we tested the activity of a new polymeric derivative with glycopolypeptide architecture (PAA-VC) bearing l-arginine, vancomycin, and colistin as side chains acting against multiple targets, which give rise to a broad spectrum antimicrobial activity favorably combining specific and n…

Enhanced adhesion and in situ photothermal ablation of cancer cells in surface-functionalized electrospun microfiber scaffold with graphene oxide

The physicochemical characteristics of a biomaterial surface highly affect the interaction with living cells. Recently, much attention has been focused on the adhesion properties of functional biomaterials toward cancer cells, since is expected to control metastatic spread of a tumor, which is related to good probability containing the progression of disease burden. Here, we designed an implantable poly(caprolactone)-based electrospun microfiber scaffold, henceforth PCLMF-GO, to simultaneously capture and kill cancer cells by tuning physicochemical features of the hybrid surface through nitrogen plasma activation and hetero-phase graphene oxide (GO) covalent functionalization. The surface i…

Cholesterol-Inulin Conjugates for Efficient SN38 Nuclear Delivery: Nanomedicines for Precision Cancer Therapy

An amphiphilic inulin-thiocholesterol conjugate (INU-Cys-TC) was strategically designed as a biodegradable core-shell nanocarrier of 7-ethyl-10-hydroxy-camptothecin (SN38) to enhance its solubility and stability in aqueous media, thus exploiting its brilliant anticancer effect. INU-Cys-TC was designed to have the hydrophilic inulin backbone (external shell) partially functionalized with hydrophobic thiocholesterol moieties (internal core) through a biodegradable disulfide bond due to cysteamine bridges. Thiocholesterol moieties impair redox-sensitive self-assembling abilities, yielding to nano-sized micelles in aqueous media capable of efficiently encapsulating a high amount of SN38 (DL = 8…

L -lysine and EDTA polymer mimics as resins for the quantitative and reversible removal of heavy metal ion water pollutants

Traditional precipitation methods for inorganic micropollutant removal from waters are increasingly being replaced by sorption methods based on both natural and synthetic materials. In this context, two novel effective heavy metal ions absorbers are presented. These resins, LYMA and LMT85, were crosslinked poly(amidoamine)s carrying amine and carboxyl groups in their repeating units. In particular, the LYMA-repeating unit contains one carboxyl and two amine groups and is a mimic of L-lysine, whereas LMT85 contains two amine and five carboxyl groups and is a mimic of EDTA. Both resins were prepared at moderate cost by simple eco-friendly procedures. The heavy metal ion set adopted as benchma…

Degradable poly(amidoamine) hydrogels as scaffolds for in vitro culturing of peripheral nervous system cells.

This paper reports on the synthesis and physico-chemical, mechanical, and biological characterization of two sets of poly(amidoamine) (PAA) hydrogels with potential as scaffolds for in vivo peripheral nerve regeneration. They are obtained by polyaddition of piperazine with N,N′-methylenebis(acrylamide) or 1,4-bis(acryloyl)piperazine with 1,2-diaminoethane as cross-linking agent and exhibit a combination of relevant properties, such as mechanical strength, biocompatibility, biodegradability, ability to induce adhesion and proliferation of Schwann cells (SCs) preserving their viability. Moreover, the most promising hydrogels, that is those deriving from 1,4-bis(acryloyl)piperazine, allow the …

Nanosystem for diagnosis and photothermal treatment of tumors

The invention relates to a nanosystem for the diagnosis, image-guided treatment of tumors and monitoring of the tumor microenvironment. The nanosystem is a contrast agent comprising a polymer shell based on a hyaluronic acid nanogel, super-parameg-netic iron oxide nanoparticles (SPIONs) and carbon nanoparticles (CDs).

Ultrafast Interface Charge Separation in Carbon Nanodot-Nanotube Hybrids

Carbon dots are an emerging family of zero-dimensional nanocarbons behaving as tunable light harvesters and photoactivated charge donors. Coupling them to carbon nanotubes, which are well-known electron acceptors with excellent charge transport capabilities, is very promising for several applications. Here, we first devised a route to achieve the stable electrostatic binding of carbon dots to multi- or single-walled carbon nanotubes, as confirmed by several experimental observations. The photoluminescence of carbon dots is strongly quenched when they contact either semiconductive or conductive nanotubes, indicating a strong electronic coupling to both. Theoretical simulations predict a favo…

Near-Infrared, Light-Triggered, On-Demand Antiinflammatories and Antibiotics Release by Graphene Oxide/Elecrospun PCL Patch for Wound Healing

Very recently, significant attention has been focused on the adsorption and cell adhesion properties of graphene oxide (GO), because it is expected to allow high drug loading and controlled drug release, as well as the promotion of cell adhesion and proliferation. This is particularly interesting in the promotion of wound healing, where antibiotics and anti-inflammatories should be locally released for a prolonged time to allow fibroblast proliferation. Here, we designed an implantable patch consisting of poly(caprolactone) electrospun covered with GO, henceforth named GO&ndash

Printable Thermo- and Photo-stable Poly(D,L-lactide)/Carbon Nanodots Nanocomposites via Heterophase Melt-Extrusion Transesterification

We propose for the first time an one-pot synthesis of carbon nanodots-poly(D,L-lactide) (CDs-PLA) nanocomposites, obtained by a simple reactive melt-extrusion process involving polar surface groups of multicolor CDs and ester bonds of PLA chains. Apart from providing an excellent method to produce polyester-coated CDs, our protocol allows obtaining perfect PLA@CDs blends giving rise to homogeneous extruded PLA@CDs filaments (ePLA@CDs) suitable for 3D printing applications (e.g., additive manufacturing for biomaterials and biodegradable encoded polymer ink technology). We demonstrate that ePLA@CDs filaments can be used to build a huge range of fluorescent objects with increasing architectura…

Functionalization of Metal and Carbon Nanoparticles with Potential in Cancer Theranostics

Cancer theranostics is a new concept of medical approach that attempts to combine in a unique nanoplatform diagnosis, monitoring and therapy so as to provide eradication of a solid tumor in a non-invasive fashion. There are many available solutions to tackle cancer using theranostic agents such as photothermal therapy (PTT) and photodynamic therapy (PDT) under the guidance of imaging techniques (e.g., magnetic resonance—MRI, photoacoustic—PA or computed tomography—CT imaging). Additionally, there are several potential theranostic nanoplatforms able to combine diagnosis and therapy at once, such as gold nanoparticles (GNPs), graphene oxide (GO), superparamagnetic iron oxide nanoparticles (SP…

Atmospheric pressure non-equilibriumplasma for the production of composite materials

In the evolving field of tissue engineering, continuous advances are required to improve scaffold design and fabrication to obtain biomimetic supports for cell adhesion, proliferation, penetration and differentiation. Both electrospun fibrous scaffolds and hydrogels are used in this field since they well reproduce the structure of the extracellular matrix (ECM) of many biological tissues. Limitations of these two types of materials can be overcome through their combination, by developing composite structures combining enhanced mechanical properties (provided by the fibrous components) and improved cell penetration (provided by the gel phase) in a superior ability to mimic natural ECM that i…

Metallic core nano-devices as drug delivery systems

Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy

The biopharmaceutical properties of supramolecular vesicular aggregates (SVAs) were characterized with regard to their physicochemical features and compared with cationic liposomes (CLs). Neutral and cationic SVAs were synthesized using two different copolymers of poly(aspartyl hydrazide) by thin-layer evaporation and extrusion techniques. Both copolymers were self-assembled in pre-formulated liposomes and formed neutral and cationic SVAs. Gemcitabine hydrochloride (GEM) was used as an anticancer drug and loaded by a pH gradient remote loading procedure, which significantly increased drug loading inside the SVAs. The resulting average size of the SVAs was 100 nm. The anticancer activity of …

Photothermal Ablation of Cancer Cells Using Folate-Coated Gold/ Graphene Oxide Composite

Objective: A new tumor targeted polymer-coated gold/graphene hybrid has been developed for achieving simultaneously thermoablation and chemoterapy of folate receptor-positive cancer cells. Methods: The gold/graphene hybrid was prepared by depositing gold nanospheres onto graphene oxide and coating it with an inulin-folate conjugate. Paclitaxel was loaded by sonication. The hybrid was characterized by UV-Vis spectroscopy, DSC analysis and SEM microscopy. The cytotoxicity, thermoablation and anticancer activity were evaluated in vitro on MCF-7 and 16 HBE. Results: In vitro tests showed that the paclitaxel-loaded hybrid improved the effectiveness of the drug especially after photothermal treat…

β-C3N4 Nanocrystals: Carbon Dots with Extraordinary Morphological, Structural, and Optical Homogeneity

Carbon nanodots are known for their appealing optical properties, especially their intense fluorescence tunable in the visible range. However, they are often affected by considerable issues of optical and structural heterogeneity, which limit their optical performance and limit the practical possibility of applying these nanoparticles in several fields. Here we developed a synthesis method capable of producing a unique variety of carbon nanodots displaying an extremely high visible absorption strength (ε > 3 × 106 M(dot)−1 cm−1) and a high fluorescence quantum yield (73%). The high homogeneity of these dots reflects in many domains: morphological (narrow size distribution), structural (q…

POLYASPARTAMIDE-POLYLACTIDE GRAFT COPOLYMERS WITH TUNABLE PROPERTIES FOR THE REALIZATION OF FLUORESCENT NANOPARTICLES FOR IMAGING

Here, the synthesis and the characterization of novel amphiphilic graft copolymers with tunable properties, useful in obtaining polymeric fluorescent nanoparticles for application in imaging, are described. These copolymers are obtained by chemical conjugation of rhodamine B (RhB) moieties, polylactic acid (PLA), and O-(2-aminoethyl)-O'-methyl poly(ethylene glycol) (PEG) on α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA). In particular, PHEA is first functionalized with RhB to obtain PHEA-RhB with a derivatization degree in RhB (DDRhB ) equal to 0.55 mol%. By varying the reaction conditions, different amounts of PLA are grafted on PHEA-RhB to obtain PHEA-RhB-PLA with DDPLA equal to 1.9, 4…

Fabrication of silver nanoparticles by a diethylene triamine-hyaluronic acid derivative and use as antibacterial coating

In this work a synthetic protocol for the functionalization of hyaluronic acid with diethylenetriamine (DETA) was standardized. HA-DETA derivatives were characterized by NMR and proton carbon correlation analysis HSQC and HMBC to confirm chemical structure. A selected derivative was used to set up a green fabrication procedure for HA-DETA capped silver nanoparticles with the aim to achieve a polymeric based coating with potential application in the treatment of medical devices associated infections. Data from UV-visible spectroscopy, electron scanning and transmission microscope (STEM), photoelectric spectroscopy (XPS) and rheological characterization were combined to characterize the HA-DE…

A multifunctional peptidomimetic macromolecule to fight polymicrobial infections

Decagram-Scale Synthesis of Multicolor Carbon Nanodots: Self-Tracking Nanoheaters with Inherent and Selective Anticancer Properties

Carbon nanodots (CDs) are a new class of carbon-based nanoparticles endowed with photoluminescence, high specific surface area, and good photothermal conversion, which have spearheaded many breakthroughs in medicine, especially in drug delivery and cancer theranostics. However, the tight control of their structural, optical, and biological properties and the synthesis scale-up have been very difficult so far. Here, we report for the first time an efficient protocol for the one-step synthesis of decagram-scale quantities of N,S-doped CDs with a narrow size distribution, along with a single nanostructure multicolor emission, high near-infrared (NIR) photothermal conversion efficiency, and sel…

Graphene oxide surface functionalization of polymeric scaffolds for the recruitment and thermal ablation of tumor cells

Surfactant effect on the physicochemical characteristics of cationic solid lipid nanoparticles

Solid lipid nanoparticles (SLNs) may be considered as a new approach for therapeutics for many diseases. In addition to drug delivery, their use as non-viral vectors for gene delivery can be obtained by including cationic lipids, which provide a positive surface potential that favors binding to the nucleic acids as DNA, siRNA, miRNA, etc. In fact, the addition of cationic surfactants is indispensable for obtaining nanoparticles with surface positive charge. In this study, three different cationic lipids (dioctadecyl dimethyl ammonium bromide, cetyltrimethyl ammonium bromide, cetylpyridinium chloride) and Brij 76 as nonionic surfactant were employed to formulate Precirol ATO 5 based cSLN usi…

Arginine-Rich Peptidomimetic Ampicillin/Gentamicin Conjugate To Tackle Nosocomial Biofilms: A Promising Strategy To Repurpose First-Line Antibiotics

: Combined therapy with penicillins and aminoglycosides has been proved beneficial to address many persistent bacterial infections with possible synergistic effects. However, the different pharmacokinetic profiles of these two antibiotic classes may not guarantee a concerted spatio-temporal delivery at the site of action, decreasing the efficacy of this combination and promoting resistance. Herein, we propose a multifunctional antibiotic-polymer conjugate, designed to colocalize ampicillin and gentamicin to tackle persistent biofilm infections. The two antibacterial molecules were grafted along with the amino acid l-arginine to a biocompatible polymer backbone with peptidomimetic hydrophili…

NIR LASER-RESPONSIVE FOLATE-TARGETED GOLD NANORODS AS EFFICIENT THERANOSTIC TOOL FOR OSTEOSARCOMA TREATMENT

Folate-targeted gold nanorods (GNRs) are here proposed as selective theranostic agents for osteosarcoma treatment. Taking advantage of the attractive physiochemical and optical properties of GNRs they can be proposed as effective and selective platform to obtain a targeted intracellular drug release, photothermal therapy and cancer imaging, which may improve therapeutic outcomes of osteosarcoma. An amphiphilic polysaccharide graft-copolymer, named INU-LA-PEG-FA, and a folic acid functionalized α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA-FA), have been synthesized to act as coating agents for GNRs. The obtained polymer-coated GNRs were characterized in terms of size, shape, zeta potenti…

Clever pH-Sensitive Drug-polymer Coniugates For Targeted Cancer Therapy

Highly Homogeneous Biotinylated Carbon Nanodots: Red-Emitting Nanoheaters as Theranostic Agents toward Precision Cancer Medicine

Very recent red-emissive carbon nanodots (CDs) have shown potential as near-infrared converting tools to produce local heat useful in cancer theranostics. Besides, CDs seem very appealing for clinical applications combining hyperthermia, imaging, and drug delivery in a single platform capable of selectively targeting cancer cells. However, CDs still suffer from dramatic dot-to-dot variability issues such that a rational design of their structural, optical, and chemical characteristics for medical applications has been impossible so far. Herein, we report for the first time a simple and highly controllable layer-by-layer synthesis of biotin-decorated CDs with monodisperse size distribution, …

Hyaluronic acid dressing of Hydrophobic Carbon Nanodots: a Self-assembling Strategy of Hybrid Nanocomposites with Theranostic Potential

We propose a rational design of hyaluronic acid-dressed red-emissive carbon dots (CDs), with a well-structured hydrophobic core capable of locally delivering high amount doxorubicin (Doxo) (> 9% w/w) and heat (hyperthermia) in a light stimuli sensitive fashion. We combined in a unique micelle-like superstructure the peculiar optical properties of CDs (NIR photothermal conversion and red fluorescence) with the ability of hyaluronic acid (HA) shell of stabilizing nanomedicines in aqueous environment and recognizing cancer cells overexpressing CD44 receptors on their membranes, thus giving rise to smart theranostic agents useful in cancer imaging and NIR-triggered chemo-phototherapy of solid t…

Use of poly(amidoamine) drug conjugates for the delivery of antimalarials to Plasmodium

Current malaria therapeutics demands strategies able to selectively deliver drugs to Plasmodium-infected red blood cells (pRBCs) in order to limit the appearance of parasite resistance. Here, the poly(amidoamines) AGMA1 and ISA23 have been explored for the delivery of antimalarial drugs to pRBCs. AGMA1 has antimalarial activity per se as shown by its inhibition of the in vitro growth of Plasmodium falciparum, with an IC50 of 13.7 μM. Fluorescence-assisted cell sorting data and confocal fluorescence microscopy and transmission electron microscopy images indicate that both polymers exhibit preferential binding to and internalization into pRBCs versus RBCs, and subcellular targeting to the par…

Pressure-Dependent Tuning of Photoluminescence and Size Distribution of Carbon Nanodots for Theranostic Anticancer Applications

Carbon nanodots (CDs) have recently attracted attention in the field of nanomedicine because of the biocompatibility, cost-effective nature, high specific surface, good near infrared (NIR) photothermal conversion into heat and tunable fluorescence properties, which have paved the way toward incorporating use of CDs into innovative anticancer theranostic platforms. However, a reliable synthesis of CDs with established and controlled physiochemical proprieties is precluded owing to the lack of full manipulation of thermodynamic parameters during the synthesis, thus limiting their use in real world medical applications. Herein, we developed a robust solvothermal protocol which allow fine contr…

A facile way to build up branched high functional polyaminoacids with tunable physicochemical and biological properties

Abstract Here, for the first time, branched polyaminoacids bearing α-amino acids as side functions, namely PAA-co-AA and PGA-co-AA, are prepared by heterophase ring opening of polysuccinimide (PSI) with l -arginine or glycine in aqueous environment and at controlled pH. The modulation of the pH of the reaction leads to high-molecular-weight copolymers with tunable functionalization and, as consequence, with tailor-made physicochemical properties. Furthermore, a branched polyaminoacid carrying a preformed bioactive peptide ( l -trileucine) and l -arginine as side pendants, named PATA-co-AA, was synthesized via a similar pathway thus leading to complex biomimetic materials potentially exploit…

A self-sterilizing fluorescent Nanocomposite as versatile material with broad-spectrum Antibiofilm features

Abstract Hematogenous spread of infections from colonized central intravenous catheters or central lines is a long-recognized problem with infection rates of 2 and 6.8 per 1000 days, respectively. Besides, removal of severe microbial colonization of implanted biomaterials is still a challenge and usually requires invasive operations. Hence, on demand self-sterilizing materials are required to avoid explant of colonized biomaterials and improve patient compliance. Moreover, photoluminescence is needed to make trackable biomaterials, which can be easily monitored upon implanting them in the body. Here, we propose the incorporation of near infrared (NIR) sensitive red-emitting carbon nanodot (…

Blood N-3 fatty acids increase after consumption of an enriched yoghurt

The effects of a n-3 fatty acid (FA) enriched yoghurt on blood FA were investigated in 23 females and 23 males, who consumed 2 yoghurts/day for 6 weeks, providing 64 mg EPA and 74 mg DHA. Blood samples were collected before treatment, at the beginning, end, and after wash out. Yoghurt intakes increased blood EPA (35%) and DHA (11%) with different trends of changes in women versus men. In conclusion, the daily consumption of a yoghurt containing small amounts of n-3 FA significantly increases blood n-3 FA, providing a useful approach to reach the recommended intakes in populations.

Amino acid-­deriving chiral polymers with potential for biotechnological applications

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