Albumin-based nanoparticles combined with photodynamic therapy enhance the antitumor activity of curcumin derivative C086

Abstract C086, a derivative of curcumin, was previously identified as a novel heat shock protein 90 (Hsp90) inhibitor and was found to exhibit stronger anti-tumor activity than curcumin. However, the inferior water solubility of C086 limits both its bioavailability and therapeutic efficacy. In this study, we aimed to improve the solubility and consequently the bioavailability of C086 via the albumin-based nanoparticles (NPs). The C086-loaded human serum albumin (C086@HSA) NPs were fabricated by a simple self-assembly method. The resulting C086@HSA NPs with an average diameter size of 36 nm, combined with photodynamic therapy, showed significant cytotoxic activity against all tumor cell lines investigated along with longer duration of effect than pure C086. More investigation was carried on the anti-tumor mechanism of C086@HSA NPs, showing that its anti-tumor effect of photodynamic therapy (PDT) on human cervical carcinoma HeLa cells was associated with apoptosis and cell cycle arrest at the S and G2/M phase upon 10-min blue light illumination (450 nm, 5 mW/cm2). Furthermore, the in vivo antitumor activity of C086@HSA NPs was evaluated in 4T1 tumor-bearing mouse model using intense blue light (80 mW/cm2), confirming the enhanced antitumor activity of C086@HSA NPs through photodynamic therapy. Taken together, our work provides an efficient albumin-based nanoparticle drug delivery platform to improve the bioavailability and therapeutic efficacy of hydrophobic photosensitizers against tumor growth.