Search results for "Nanocarrier"
showing 10 items of 153 documents
Functionalization of Liposomes with Hydrophilic Polymers Results in Macrophage Uptake Independent of the Protein Corona
2019
Liposomes are established drug carriers that are employed to transport and deliver hydrophilic drugs in the body. To minimize unspecific cellular uptake, nanocarriers are commonly modified with poly(ethylene glycol) (PEG), which is known to minimize unspecific protein adsorption. However, to date, it has not been studied whether this is an intrinsic and specific property of PEG or if it can be transferred to hyperbranched polyglycerol (hbPG) as well. Additionally, it remains unclear if the reduction of unspecific cell uptake is independent of the “basic” carrier at which a surface functionalization with polymers is usually applied. Therefore, we studied the protein corona of differently fun…
Biodegradable pH-Sensitive Poly(ethylene glycol) Nanocarriers for Allergen Encapsulation and Controlled Release
2015
In the last decades, the number of allergic patients has increased dramatically. Allergen-specific immunotherapy (SIT) is the only available cause-oriented therapy so far. SIT reduces the allergic symptoms, but also exhibits some disadvantages; that is, it is a long-lasting procedure and severe side effects like anaphylactic shock can occur. In this work, we introduce a method to encapsulate allergens into nanoparticles to avoid severe side effects during SIT. Degradable nanocarriers combine the advantage of providing a physical barrier between the encapsulated cargo and the biological environment as well as responding to certain local stimuli (like pH) to release their cargo. This work int…
pH-responsive physically and chemically cross-linked glutamic-acid-based hydrogels and nanogels
2018
Abstract Given the great demand for polymers prepared from renewable materials, the synthesis of a glutamic-acid-based hydrogel by solution and inverse miniemulsion polymerization is herein presented. Free radical initiated homopolymerizations of N-acryloyl- l -glutamic acid (l- AGA) resulted in either a readily water-soluble polymer or a physically cross-linked hydrogel, being the formation of physical cross-linking junctions closely related to monomer concentration and mixture viscosity. Chemically cross-linked poly( l -AGA-co-BIS) hydrogels were also synthesized by copolymerization of l -AGA and N,N′-methylenebis(acrylamide) (BIS). Both poly (l- AGA) and poly( l -AGA-co-BIS) swelling beh…
Timing of Heparin Addition to the Biomolecular Corona Influences the Cellular Uptake of Nanocarriers.
2019
Few studies have considered the interaction of nanocarriers with drugs and the implications for their individual efficiency. Here, we demonstrate that heparin, a common anticoagulant, interacts with nanocarriers. Hence, nanocarriers, precoated with heparin and plasma in different conditions, were incubated with cancer cells, as well as primary cells from human blood. The relation between the timing of the heparin's addition to the nanocarrier and the cellular uptake extent was assessed by flow cytometry. Through proteomics the effect of heparin on the biomolecular corona composition was determined. We found that HeLa cells, monocytes and macrophages reacted differently to the presence of he…
Polyphosphoester surfactants as general stealth coatings for polymeric nanocarriers
2020
Opsonization of nanocarriers is one of the most important biological barriers for controlled drug delivery. The typical way to prevent such unspecific protein adsorption and thus fast clearance by the immune system is the covalent modification of drug delivery vehicles with poly(ethylene glycol) (PEG), so-called PEGylation. Recently, polyphosphoesters (PPEs) were identified as adequate PEG substitutes, however with the benefits of controllable hydrophilicity, additional chemical functionality, or biodegradability. Here, we present a general strategy by non-covalent adsorption of different nonionic PPE-surfactants to nanocarriers with stealth properties. Polyphosphoester surfactants with dif…
Molecular insights and novel approaches for targeting tumor metastasis
2020
In recent years, due to the effective drug delivery and preciseness of tumor sites or microenvironment, the targeted drug delivery approaches have gained ample attention for tumor metastasis therapy. The conventional treatment approaches for metastasis therapy have reported with immense adverse effects because they exhibited maximum probability of killing the carcinogenic cells along with healthy cells. The tumor vasculature, comprising of vasculogenic impressions and angiogenesis, greatly depends upon the growth and metastasis in the tumors. Therefore, various nanocarriers-based delivery approaches for targeting to tumor vasculature have been attempted as efficient and potential approaches…
Squaric Ester-Based, pH-Degradable Nanogels: Modular Nanocarriers for Safe, Systemic Administration of Toll-like Receptor 7/8 Agonistic Immune Modula…
2021
Small-molecular Toll-like receptor 7/8 (TLR7/8) agonists hold promise as immune modulators for a variety of immune therapeutic purposes including cancer therapy or vaccination. However, due to their rapid systemic distribution causing difficult-to-control inflammatory off-target effects, their application is still problematic, in particular systemically. To address this problem, we designed and robustly fabricated pH-responsive nanogels serving as versatile immunodrug nanocarriers for safe delivery of TLR7/8-stimulating imidazoquinolines after intravenous administration. To this aim, a primary amine-reactive methacrylamide monomer bearing a pendant squaric ester amide is introduced, which i…
Hydrophilicity Regulates the Stealth Properties of Polyphosphoester‐Coated Nanocarriers
2018
Increasing the plasma half-life is an important goal in the development of drug carriers, and can be effectively achieved through the attachment of polymers, in particular poly(ethylene glycol) (PEG). While the increased plasma half-life has been suggested to be a result of decreased overall protein adsorption on the hydrophilic surface in combination with the adsorption of specific proteins, the molecular reasons for the success of PEG and other hydrophilic polymers are still widely unknown. We prepared polyphosphoester-coated nanocarriers with defined hydrophilicity to control the stealth properties of the polymer shell. We found that the log P value of the copolymer controls the composit…
Denaturation via Surfactants Changes Composition of Protein Corona
2018
The use of nanocarriers as drug delivery vehicles brings them into contact with blood plasma proteins. Polymeric nanocarriers require some sort of surfactant to ensure colloidal stability. Formation of the protein corona is therefore determined not only by the intrinsic properties of the nanocarrier itself but also by the accompanying surfactant. Although it is well-known that surfactants have an impact on protein structure, only few studies were conducted on the specific effect of surfactants on the composition of protein corona of nanocarriers. Therefore, we analyzed the composition of the protein corona on "stealth" nanoparticles with additional surfactant (cetyltrimethylammonium chlorid…
Preparation of the Protein Corona: How Washing Shapes the Proteome and Influences Cellular Uptake
2020
A protein coat, termed the protein corona, assembles around the nanocarriers´ surface once it gets in contact with a biological environment. We show that the media used for washing of the protein corona can be crucial. This is true for downstream analysis as well as for precoating for in vitro or in vivo use. This has been widely overlooked so far. We focus on the choice of eight different washing media and how they influence the composition of the hard protein corona of several nanocarriers incubated with human blood plasma and serum. SDS-PAGE and LC-MS analysis showed major differences in protein corona profiles when using diverse washing media. While plasma and serum proteins already hav…