Beta-carotene-bound albumin nanoparticles modified with chlorin e6 for breast tumor ablation based on photodynamic therapy

Abstract

Chlorin e6 (Ce6) has attracted considerable interest as a promising second-generation photosensitizer for photodynamic therapy (PDT). However, the in vivo availability of Ce6 is significantly restricted by its low water solubility and poor ability to target tumors. We sought to overcome the limitations of Ce6 by using albumin nanoparticles with nab (TM) (nanoparticle albumin-bound) technology. The fabricated albumin nanoparticles consisted of bovine serum albumin (BSA), Ce6-BSA, and beta-carotene as a carrier, photosensitizing agent, and cross-linker, respectively. These albumin nanoparticles (Ce6-BSA-BC-NPs) did not include any toxic chemotherapeutics but instead contained naturally safe beta-carotene and Ce6, which was activated only upon irradiation with 660-nm laser light. Ce6-BSA-BC-NPs were similar to 120 nm in size and spherical, similar to Abraxane (R), and showed good physicochemical stability. The nanoparticles showed significant cytotoxicity toward 4T1 cells as evaluated by MTT, Live/Dead, and TUNEL assays. In particular, results of the TUNEL assay demonstrated that cell death induced by Ce6-BSA-BC-NPs and light irradiation (660 nm) occurred through the apoptotic pathway. Ce6-BSA-BC-NPs displayed a remarkably enhanced tumor suppression effect when irradiated by 660-nm light compared with free Ce6 (tumor volume 90 +/- 39 versus 487 +/- 69 mm(3) respectively). Overall, this improved in vivo antitumor efficacy seemed to be due to the targetability of albumin nanoparticles. We believe that our Ce6-BSA-BC-NPs with PDT offer a promising new potential therapeutic platform for breast cancer treatment.