Abstract
A charge-conversional and NIR responsive rapid release liposomal system (PSD/DOX/Cypate-BTSL) was developed to enhance therapeutic efficacy of cancer therapy. The cationic liposomes containing Cypate, doxorubicin (DOX) and NH4HCO3 were shielded by pH-sensitive poly(methacryloyl sulfadimethoxine) (PSD) through electrostatic interaction at pH 7.4. At the tumor site (pH 6.5), PSD was deshielded and the liposomes displayed pH-sensitive charge reversal capability. The DOX released from PSD/DOX/Cypate-BTSL with irradiation was markedly higher than the other groups, indicating NIR irradiation and NH4HCO3 had a significant effect on the drug release. After irradiation, the hyperthermia induced by Cypate could produce CO2 bubbles quickly on account of the decomposition of NH4HCO3, achieving the rapid drug release. In 4T1 cells, PSD/DOX/Cypate-BTSL improved cellular uptake and cytotoxicity with irradiation at pH 6.5. In vivo results implied that the liposomes with irradiation could efficiently enhance the tumor accumulation and antitumor efficacy, and reduce systemic side effects of DOX. In conclusion, PSD/DOX/Cypate-BTSL is a promising candidate as a carrier for synergistic effects of PTT and chemotherapy.
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