pH-sensitive short worm-like micelles targeting tumors based on the extracellular pH

초록

We developed novel photosensitizing drug-carrying worm-like micelles using a pH-sensitive AB(2) miktoarm block copolymer consisting of one methoxy-poly(ethylene glycol) (mPEG) block (A) and two 3-diethylaminopropylated poly(L-lysine) [poly(Lys-DEAP)] blocks (B-2). In particular, the Y-shaped AB(2) miktoarm block copolymer structure mimicking the phospholipid structure enabled the facile preparation of worm-like micelles. The unique feature of pH-responsive DEAP as a hydrophobic moiety (non-protonated DEAP) at pH 7.4 and as a hydrophilic moiety (protonated DEAP) at pH 6.8 modulated acidic pH-activated micellar disintegration. These worm-like micelles serve as a basic transformer whose assembled conformation disintegrates in the acidic milieu (similar to pH 6.8) of solid tumors, resulting in improved phototoxicity due to triggered drug release from disintegrated micelles at acidic tumor sites and high-yield generation of cytotoxic singlet oxygen from the photosensitizing drug. As a result, the tumor volume in the nude mice treated with these worm-like micelles was approximately 5.2 times smaller than those treated with free drug. We anticipate that this system will provide great potential for tumor therapy.

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