Abstract
A surface charge-switched polymeric micelle with a pH signal was developed as a drug-carrying nanovehicle for tumor targeting. The micelles (particle size: ∼85 nm), constructed from poly( l-lactic acid)- b-poly(ethylene glycol)- b-poly( l-lysine-N ɛ-(2,3-dimethyl maleic acid)) (PLA- b-PEG- b-PLys-DMA) and formed by self-assembly in an aqueous pH 7.4 solution, consisted of a hydrophobic core (PLA core) and two hydrophilic shells (PEG shell and PLys-DMA shell). An anionic charge can be built on the surface of the micelle at a physiological pH (∼pH 7.4) due to 2,3-dimethyl maleic acid (DMA). However, DMA becomes chemically dissociated from the micelle under mild acidic conditions (pH 6.5–7.0) such as that found in solid tumors, which results in the formation of a cationic surface due to the poly( l-lysine) (PLys). This pH-triggered switch in surface charge may enhance cellular uptake of micelles to solid tumors, via an adsorptive endocytotic pathway due to the electrostatic interaction between micelles and cells. In addition, blending of the poly( l-histidine) (polyHis) into the hydrophobic core provides a mechanism for endosomal pH-triggered drug-release from the polymeric micelle. These combined properties of the polymeric micelle may aid in tumor-specific drug accumulation and allow it to be used as an effective treatment for tumors.
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