In this paper, biodegradable amphiphilic block copolymer based on methoxy poly(ethylene glycol)-b-poly(5-allyloxy-1,3-dioxan-2-one) (mPEG-b-PATMC) was successfully synthesized in bulk using immobilized porcine pancreas lipase (IPPL) as the catalyst. After thiol-ene "click" reactions occur between thiol group of thioglycolic acid and carbon-carbon double bonds of PATMC segments, the pendent carboxyl-modified copolymer mPEG-b-PATMC-g-SCH2COOH was obtained for high-efficiency loading and controlled release of doxorubicin (DOX) to cancer cells. Both the carboxyl-modified and unmodified copolymers could self-assemble to form nano-sized micelles in aqueous solution, while transmission electron microscopy (TEM) observation showed that the micelles dispersed in spherical shape with nano-size before and after DOX loading. Compared with the unmodified copolymer, the pendent carboxyl-modified structure in mPEG-b-PATMC-g-SCH2COOH could markedly enhance the drug-loading capacity and entrapment efficiency via the electrostatic interaction. The in vitro release studies showed more sustained drug release behavior of mPEG-b-PATMC-g-SCH2COOH without an initial burst, which could be further adjusted by the conditions of ionic strength and pH. Confocal laser scanning microscopy (CLSM) indicated efficient cellular uptake of DOX delivered by mPEG-b-PATMC-g-SCH2COOH, while MTT assays also demonstrated potent cytotoxic activity against HeLa cells.