Self-Assembled Carrier-Free Nanodrugs for Starvation Therapy-Amplified Photodynamic Therapy of Cancer

Traditional starvation treatment strategies, which involve glucose oxidase and drug-induced thrombi, often suffer from aggravated tumor hypoxia and have failed to improve antitumor efficacy in combination with oxygen-dependent photodynamic therapy (PDT). Herein, glucose transporter 1 inhibitor genistein (Gen) and photosensitizer chlorin e6 (Ce6) are integrated to construct carrier-free self-assembled nanoparticles defined as GC NPs, for starvation therapy-amplified PDT of tumor. GC NPs with regular morphology and stability are screened out by component adjustment, while the function of each component is preserved. On the one hand, Gen released from GC NPs can cut off tumor glucose uptake by inhibiting the glucose transporter 1 to restrict tumor growth, achieving starvation therapy. On the other hand, they are able to decrease the amount of oxygen consumed by tumor respiration and amplify the therapeutic effect of PDT. In vitro and in vivo experiments verify the excellent synergistic antitumor therapeutic efficacy of GC NPs without any apparent toxicity. Moreover, fluorescence and photoacoustic imaging provide guidance for in vivo PDT, demonstrating the excellent tumor enrichment efficiency of GC NPs. It is believed that this starvation therapy-amplified PDT strategy by carrier-free self-assembled GC NPs holds promising clinical prospects.

Automated summary

In this study, carrier-free self-assembled nanoparticles, GC NPs, were developed by integrating glucose transporter 1 inhibitor genistein (Gen) and photosensitizer chlorin e6 (Ce6). GC NPs effectively cut off tumor glucose uptake and reduce tumor oxygen consumption, enhancing the therapeutic effect of photodynamic therapy (PDT). In vitro and in vivo experiments demonstrated the excellent synergistic antitumor efficacy of GC NPs without apparent toxicity. Moreover, fluorescence and photoacoustic imaging showed the excellent tumor enrichment efficiency of GC NPs, providing guidance for in vivo PDT. This carrier-free self-assembled GC NPs strategy holds promising clinical prospects for starvation therapy-amplified PDT.