Various chemical and biological strategies have been used to improve tumor targeting for anticancer drug delivery. The pathological tissues often have a local temperature elevated up to 40-42°C compared to unaffected organs due to high glycolysis rate and fast proliferation of cancer cells. We report on the dual pH- and temperature-responsive polymersomes of poly(N-vinyl-caprolactam)n-b-poly(dimethylsiloxane)m-b-poly (N-vinylcaprolactam)n (PVCLn-PDMSm-PVCLn) triblock copolymers for encapsulation and pH-triggered release of doxorubicin. The PVCL10-b-PDMS65-b-PVCL10 and PVCL6-b-PDMS65-b-PVCL6 triblock copolymers can assemble into a stable vesicular structure with average sizes of 480 nm and 280 nm, respectively, at room temperature and encapsulate the anticancer drug doxorubicin (DOX). The diameter of the PVCL10-b-PDMS65-b-PVCL10 polymersomes decreased from 480 to 110 nm upon 5-hour incubation at pH=3 due to hydrolysis of ester bonds facilitating fast drug release of ~87% DOX within 12 hours of incubation. We explored the effect of the chain length of the blocks on the vesicle degradation and the DOX release and found that the vesicles with longer PVCL chains provided a faster drug release rate due to greater changes within the shell structure at 42 °C and pH=3. In vivo toxicity studies using a C57BL/6J mouse model along with hematology, necropsy and gravimetric analyses suggest that PVCL10-b-PDMS65-b-PVCL10 polymersomes are biocompatible and measured parameters were in physiological range. Our results provide evidence of biocompatibility and in vivo biodegradability of these dual-responsive polymersomes and show promise for the development of advanced nanocarriers for anticancer therapy.

Biodegradable temperature responsive polymersomes for triggered anticancer drug release

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.