Abstract
PURPOSE: Photothermal therapy (PTT) is promising for the treatment of tumors due to its advantages including minimally invasive, easy implementation and selective localized treatment. However, single PTT suffers from several limitations, such as constrained light penetration and low delivery efficiency, typically leading to heterogeneous heating and incomplete elimination of cancer cells. Therefore, combination of PTT with other therapies, eg, chemotherapy is desirable in order to achieve synergistic effects in cancer treatment. METHODS: Here, we designed a new type of TCPP-Iso combined nanoparticle for synergetic therapy for breast cancer. Specifically, photothermal agent tetra(4-carboxyphenyl) porphine (TCPP) and anti-cancer drug isoliensinine (Iso) were encapsulated in PEG-b-PLGA polymeric nanoparticles through a precipitation process. RESULTS: The obtained NPs displayed well-controlled size and high stability over time. Tuning TCPP-Iso/polymer ratio, or total concentration of drug and polymers led to increased hydrodynamic radius of NPs from 65 to 108 nm without disturbing the narrow size distribution. Besides, the formed NPs showed a consequently cumulative release of TCPP and of Iso. The temperature elevation ability of both TCPP NPs and TCPP-Iso NPs was TCPP-concentration dependent. Solutions of TCPP NPs that contained equivalent amount of TCPP with respect to TCPP-Iso NPs, presented the same trend and exhibited non-obvious difference in temperature elevation under certain laser power. The viability of MDA-MB-231 cells treated with TCPP-Iso NPs could be inhibited effectively at a relatively mild temperature (42-43°C) compared to the other groups, which may minimize heat damage to the surrounding healthy tissues. CONCLUSION: The results indicate that the TCPP-Iso combined NPs showed hardly any toxicity to normal tissue cell line, but displayed an efficient synergistic effect for killing cancer cells under laser irradiation. Our study demonstrates that the successful combination of TCPP and Iso realized a synergistic therapy effect at a relatively mild temperature, and the insights obtained here shall be helpful for designing new combined PTT agents for cancer treatment.