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

We developed novel photosensitizing drug-carrying worm-like micelles using a pH-sensitive AB₂ miktoarm block copolymer consisting of one methoxy-poly(ethylene glycol) (mPEG) block (A) and two 3-diethylaminopropylated poly(L-lysine) [poly(Lys-DEAP)] blocks (B₂). In particular, the Y-shaped AB₂ 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 (∼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.