Sustained-release behavior and the antitumor effect of charge-convertible poly(amino acid)s drug-loaded nanoparticles

Enhancing tissue permeability and achieving drug aggregation is the key to targeted tumor therapy. A series triblock copolymers of poly(ethylene glycol)-poly(L-lysine)-poly(L-glutamine) were synthesized by ring-opening polymerization, and charge-convertible nano-delivery system was constructed by loading doxorubicin (DOX) with 2-(hexaethylimide) ethanol on side chain. In normal environment (pH = 7.4), the zeta potential of the drug-loaded nanoparticle solution is negative, which is conducive to avoiding the identification and clearance of nanoparticles by the reticulo-endothelial system, while potential-reversal can be achieved in the tumor microenvironment, which effectively promotes cellular uptake. Nanoparticles could effectively reduce the distribution of DOX in normal tissues and achieve targeted aggregation at tumor sites, which can effectively improve the antitumor effect, while would not causing toxicity and damage to normal body. Graphical Abstract