Nanoplatform for synergistic therapy constructed via the co-assembly of a reduction-responsive cholesterol-based block copolymer and a photothermal amphiphile

The goal of combination cancer therapy, including chemo-phototherapy, is to achieve highly efficient antitumor effects while minimizing the adverse reactions associated with conventional chemotherapy. Nevertheless, enhancing the contribution of non-chemotherapeutic strategies in combination therapy is often challenging because this requires multiple active ingredients to be encapsulated in a single delivery system. However, most commonly used photothermal reagents are challenging to be loaded in large quantities and have poor biocompatibility. Herein, we developed photothermal co-micelles through a co-assembly strategy using a cholesterol-based liquid crystal block copolymer (LC-BCP) with disulfide bonds in the side chain of the LC blocks and a croconaine-based amphiphile (CBA) containing a cholesterol moiety. This approach allowed the CBA to be effectively embedded within LC-BCPs, serving as the functional component of the drug-loaded carrier. These co-micelles could encapsulate doxorubicin (DOX), showed tunable reduction-responsive drug release, and enabled near-infrared laser-triggered photothermal therapy as well as <i>in vivo</i> fluorescence and photothermal imaging. Following laser irradiation, the photothermal activity of the co-micelles rapidly induced tumor cell death and accelerated drug release. <i>In vitro</i> and <i>in vivo</i> experiments demonstrated that the synergistic photo-chemotherapeutic effects of these drug-loaded co-micelles offer a promising avenue for synergistic precision photothermal-chemotherapy.