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Peptide-Based Stealth Nanoparticles for Targeted and pH-Triggered Delivery.
Bioconjugate Chemistry 2017 Februrary 16
Stealth agents are extensively investigated as a means by which to prolong nanostructure residence time in the bloodstream by avoiding uptake by the reticuloendothelial system. Unfortunately, commonly used agents such as poly(ethylene glycol) can adversely impact targeting efficiency and promote immune reaction by the host organism. Therefore, there is an increasing interest in developing biocompatible, non-PEGylated organic nanostructures able to perform targeted delivery to increase the efficacy of liposomal technology. Here, a lipopeptide is presented that can be mixed with lipids commonly used in liposomal formulations in percentages ranging from 20% to 60% w/w. The resulting vesicles are thermally and chemically stable. The peptide coating limits serum-protein adsorption even upon prolonged incubation in pure serum in physiological conditions, outperforming PEGylated liposomes. This architecture can be easily modified to allow straightforward derivatization by standard bio-orthogonal conjugation. Upon derivatization with an anti-transferrin receptor aptamer, these vesicles show highly selective cellular internalization with minimal nonspecific uptake and pH-triggered doxorubicin release.
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