pH-responsive polymer–drug conjugates as multifunctional micelles for cancer-drug delivery

We developed a novel linear pH-sensitive conjugate methoxy poly(ethylene glycol)-4 β -aminopodophyllotoxin (mPEG-NPOD-I) by a covalently linked 4 β -aminopodophyllotoxin (NPOD) and PEG via imine bond, which was amphiphilic and self-assembled to micelles in an aqueous solution. The mPEG-NPOD-I micelles simultaneously served as an anticancer drug conjugate and as drug carriers. As a drug conjugate, mPEG-NPOD-I showed a significantly faster NPOD release at a mildly acidic pH of 5.0 and 4.0 than a physiological pH of 7.4. Notably, it was confirmed that this drug conjugate could efficiently deliver NPOD to the nuclei of the tumor cells and led to much more cytotoxic effects to A549, Hela, and HepG2 cancer cells than the parent NPOD. The half maximal inhibitory concentration (IC 50 ) of mPEG-NPOD-I was about one order magnitude lower than that of the NPOD. In vivo , mPEG-NPOD-I reduced the size of the tumors significantly, and the biodistribution studies indica...

Yang Kang, Wei Ha, Ying-Qian Liu, Yuan Ma, Min-Min Fan, Li-Sheng Ding, Sheng Zhang and Bang-Jing Li

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