Search results for "Targeted drug delivery"
showing 10 items of 56 documents
Loading and release of the complex [Pt(DTBTA)(DMSO)Cl]Cl·CHCl3 with the 2,2′-dithiobis(benzothiazole) ligand into mesoporous silica and studies of an…
2018
Abstract Synthetic delivery systems have great potential for overcoming problems associated with systemic toxicity that accompanies chemotherapy with the use of cisplatin and family of platinum anticancer drugs. Mesoporous silicates have been studied in context of drug delivery and drug targeting. In this paper we report the studies of loading and release of a platinum complex, [Pt(DTBTA)(DMSO)Cl]Cl∙CHCl3 (1) where DTBTA = 2,2′-dithiobis(benzothiazole), that was recently synthesized and structurally characterized. Evaluation in vitro of antitumor activity against a human breast cancer cell line (MCF-7) showed a very potent activity of complex(1). Therefore, we thought to incorporate this co…
Ticket to Ride: Targeting Proteins to Exosomes for Brain Delivery.
2017
Exosomes represent an attractive vehicle for the delivery of biomolecules. However, mechanisms for loading functional molecules into exosomes are relatively unexplored. Here we report the use of the evolutionarily conserved late-domain (L-domain) pathway as a mechanism for loading exogenous proteins into exosomes. We demonstrate that labeling of a target protein, Cre recombinase, with a WW tag leads to recognition by the L-domain-containing protein Ndfip1, resulting in ubiquitination and loading into exosomes. Our results show that Ndfip1 expression acts as a molecular switch for exosomal packaging of WW-Cre that can be suppressed using the exosome inhibitor GW4869. When taken up by floxed …
Albumin-Folate Conjugates for Drug-targeting in Photodynamic Therapy.
2016
Photodynamic therapy (PDT) is based on the cytotoxicity of photosensitizers in the presence of light. Increased selectivity and effectivity of the treatment is expected if a specific uptake of the photosensitizers into the target cells, often tumor cells, can be achieved. An attractive transporter for that purpose is the folic acid receptor α (FRα), which is overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe the synthesis and photobiological characterization of polar β-carboline derivatives as photosensitizers covalently linked to folate-tagged albumin as the carrier system. The particles were taken up by KB (human carcinoma) cells within …
Nanoparticle delivery to metastatic breast cancer cells by nanoengineered mesenchymal stem cells
2017
We created a 3D cell co-culture model by combining nanoengineered mesenchymal stem cells (MSCs) with the metastatic breast cancer cell line MDA-MD-231 and primary breast cancer cell line MCF7 to explore the transfer of quantum dots (QDs) to cancer cells. First, the optimal conditions for high-content QD loading in MSCs were established. Then, QD uptake in breast cancer cells was assessed after 24 h in a 3D co-culture with nanoengineered MSCs. We found that incubation of MSCs with QDs in a serum-free medium provided the best accumulation results. It was found that 24 h post-labelling QDs were eliminated from MSCs. Our results demonstrate that breast cancer cells efficiently uptake QDs that a…
Aptamers as smart ligands for nano-carriers targeting
2016
The development of enhanced drug delivery systems is one of the most attractive fields of pharmaceutical sciences, as some of the highly effective chemo/biotherapeutics for cancer treatment can not be administrated due to their high toxicities for normal cells or low stability in physiological media. However, drugs that are currently not administrable will become valuable if specific cell-targeted drug carriers can protect the normal cells from adverse effects and also improve drug pharmacokinetics. Aptamers are attractive and promising biomaterials developed with high affinity and specificity against numerous valuable targets. They could act similar to monoclonal antibodies (mAbs), and off…
Nano-engineered skin mesenchymal stem cells: potential vehicles for tumour-targeted quantum-dot delivery
2017
Nanotechnology-based drug design offers new possibilities for the use of nanoparticles in imaging and targeted therapy of tumours. Due to their tumour-homing ability, nano-engineered mesenchymal stem cells (MSCs) could be utilized as vectors to deliver diagnostic and therapeutic nanoparticles into a tumour. In the present study, uptake and functional effects of carboxyl-coated quantum dots QD655 were studied in human skin MSCs. The effect of QD on MSCs was examined using a cell viability assay, Ki67 expression analysis, and tri-lineage differentiation assay. The optimal conditions for QD uptake in MSCs were determined using flow cytometry. The QD uptake route in MSCs was examined via fluore…
E-beam crosslinked nanogels conjugated with monoclonal antibodies in targeting strategies
2017
Abstract Poly(N-vinyl pyrrolidone)-based-nanogels (NGs), produced by e-beam irradiation, are conjugated with monoclonal antibodies (mAb) for active targeting purposes. The uptake of immuno-functionalized nanogels is tested in an endothelial cell line, ECV304, using confocal and epifluorescence microscopy. Intracellular localization studies reveal a faster uptake of the immuno-nanogel conjugate with respect to the ‘bare’ nanogel. The specific internalization pathway of these immuno-nanogels is clarified by selective endocytosis inhibition experiments, flow cytometry and confocal microscopy. Active targeting ability is also verified by conjugating a monoclonal antibody which recognizes the αv…
Treatment of advanced gastroenteropancreatic neuroendocrine neoplasia, are we on the way to personalised medicine?
2021
Gastroenteropancreatic neuroendocrine neoplasia (GEPNEN) comprises clinically as well as prognostically diverse tumour entities often diagnosed at late stage. Current classification provides a uniform terminology and a Ki67-based grading system, thereby facilitating management. Advances in the study of genomic and epigenetic landscapes have amplified knowledge of tumour biology and enhanced identification of prognostic and potentially predictive treatment subgroups. Translation of this genomic and mechanistic biology into advanced GEPNEN management is limited. ‘Targeted’ treatments such as somatostatin analogues, peptide receptor radiotherapy, tyrosine kinase inhibitors and mammalian target…
Targeted-lung delivery of dexamethasone using gated mesoporous silica nanoparticles. A new therapeutic approach for acute lung injury treatment
2021
Acute lung injury (ALI) is a critical inflammatory syndrome, characterized by increased diffuse inflammation and severe lung damage, which represents a clinical concern due to the high morbidity and mortality in critical patients. In last years, there has been a need to develop more effective treatments for ALI, and targeted drug delivery to inflamed lungs has become an attractive research field. Here, we present a nanodevice based on mesoporous silica nanoparticles loaded with dexamethasone (a glucocorticoid extensively used for ALI treatment) and capped with a peptide that targets the TNFR1 receptor expressed in pro-inflammatory macrophages (TNFR-Dex-MSNs) and avoids cargo leakage. TNFR-D…
Selective adsorption of oppositely charged PNIPAAM on halloysite surfaces: a route to thermo-responsive nanocarriers.
2018
Halloysite nanotubes were functionalized with stimuli-responsive macromolecules to generate smart nanohybrids. Poly(N-isopropylacrylamide)-co-methacrylic acid (PNIPAAM-co-MA) was selectively adsorbed into halloysite lumen by exploiting electrostatic interactions. Amine-terminated PNIPAAM polymer was also investigated that selectively interacts with the outer surface of the nanotubes. The adsorption site has a profound effect on the thermodynamic behavior and therefore temperature responsive features of the hybrid material. The drug release kinetics was investigated by using diclofenac as a non-steroidal anti-inflammatory drug model. The release kinetics depends on the nanoarchitecture of th…