Chemotherapy is widely applied to treat cancer patients but its application is limited due to the systemic
toxicity and low efficacy. Nanocarrier system, which is capable of delivering their toxic cargos specifically
into cancer cells and then greatly overcomes these disadvantages, has drawn a broad attention. Here we
developed a drug-conjugated micelle for a better drug delivery in which folic acid was attached to the
DOX-conjugated poly(ethylene glycol)-poly(ε-caprolactone) to target tumor; DOX was further connected
with a hydrazone linker (FA-hyd) for a pH-triggered drug release. Comparing to other DOX-conjugated
micelles either linked with carbamate (FA-cbm) or lacking FA(m-hyd), the developed FA-hyd demonstrated
excellent biocompatibility; When analyzed with Alamar blue assays, flow cytometry and confocal
laser scanning microscopy (CLSM), the pH-sensitive FA-functionalized DOX-conjugated micelles presented
much better efficiency of cellular uptake and higher cytotoxicity to tumor cells. In vivo pharmacokinetics
and biodistribution studies indicated that FA-hyd micelles significantly prolonged the
blood circulation time of drug and enriched drug into the tumors rather than normal tissues. In vivo
antitumor activity demonstrated that FA-hyd micelles had the highest safety to body and the best
therapeutic efficacy to tumors. Therefore, this drug delivery system is deemed as a potential nanocarrier
for cancer therapy.


Xing Guo,Chunli Shi,Jie Wang,Shubin Di,Shaobing Zhou.



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