Dual chemotherapy and photodynamic therapy in an HT-29 human colon cancer xenograft model using SN-38-loaded chlorin-core star block copolymer micelles.

ABSTRACT

Chlorin-core star-shaped block copolymer (CSBC) may self-assemble to form micelles, which act as nanosized photosensitizing agents for photodynamic therapy (PDT) and further encapsulate hydrophobic drugs. This functionalized micellar delivery system is a potential dual carrier for the synergistic combination of photodynamic therapy and chemotherapy for the treatment of cancer. In this study, SN-38 encapsulated CSBC micelles were successfully prepared using a lyophilization-hydration method. Our results show that the prolonged plasma residence time of SN-38/CSBC micelles as compared with free CPT-11 permit increased tumor accumulation and consequently, improved antitumor activity. The combined effects of SN-38/CSBC micelles with PDT were evaluated in an HT-29 human colon cancer xenograft model. Interesting, SN-38/CSBC-mediated PDT synergistically inhibited tumor growth, resulting in up to 60% complete regression of well-established tumors after 3 treatments. These treatments also decreased the microvessel density (MVD) and cell proliferation within the subcutaneous tumors. Therefore, this SN-38/CBSC delivery system has the potential to offer dual therapies for the synergistic combination of PDT and chemotherapy for the treatment of cancer.