Surface-adaptive zwitterionic nanoparticles for prolonged blood circulation time and enhanced cellular uptake in tumor cells

Acta Biomaterialia
Hanlin OuLinqi Shi

Abstract

Recently, zwitterionic materials have been developed as alternatives to PEG for prolonging the circulation time of nanoparticles without triggering immune responses. However, zwitterionic coatings also hindered the interactions between nanoparticles and tumor cells, leading to less efficient uptake of nanoparticles by cancer cells. Such effect significantly limited the applications of zwitterionic materials for the purposes of drug delivery and the development to novel therapeutic agents. To overcome these issues, surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(β-amino ester) (PAE) heterogeneous surfaces were constructed. Owing to the synergistic effect of zwitterionic coatings and micro-phase-separated surfaces, PMPC mixed-shell micelles exhibited the improved blood circulation time compared to single-PEG-shell micelles (PEGSMs) and single-PMPC-shell micelles (PMPCSMs). Moreover, such MSMs can convert their surface to positively charged ones in response to the acidic tumor microenvironment, leading to a significant enhancement in cellular uptake of MSMs by tumor cells. This strategy demonstrated a general approach to enhance the cellular uptake of zwitterionic nanopa...Continue Reading

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