In vitro dual-modality chemo-photodynamic therapy via stimuli-triggered polymeric micelles

Combination therapies for cancer have attracted great attention recently due to their synergistic effects to improve the therapeutic efficacy. In order to concurrently deliver dual or multiple drugs within solid tumor and exert their therapeutic effect, developing an intelligent and safe drug delivery system is highly expected. In this work, we synthesized a series of dual thermo- and pH-responsive copolymers containing hydrophobic poly(ε-caprolactone) (PCL) and hydrophilic thermo-responsive poly(N-isopropylacrylamide) (PNIPAAm) that was copolymerized with a β-alanine-functionalized monomer (βA). Both thermo and pH-response in a suitable window for physiological environment can be achieved via adjusting the ratios of NIPAAm and acidic moieties. The chemotherapeutic drug doxorubicin (DOX) and photosensitizer (meso-tetraphenylchlorin, m-TPC) have been simultaneously encapsulated in PCL-b-P(NIPAAm-co-βA) polymeric micelles with hydrodynamic diameters around 231-269 nm. The in vitro release studies demonstrated the increased drug release at acidic pH 6. The cell viability treated with dual drug-loaded micelles showed improved therapeutic efficiency under light irradiation, indicating combined effect of DOX and m-TPC has potential as dual-modality for cancer treatment.