Self-Rectifiable and Hypoxia-Assisted Chemo-Photodynamic Nanoinhibitor for Synergistic Cancer Therapy

Abstract

Photodynamic therapy (PDT) can eradicate cancer cells under light irradiation, mainly because of reactive singlet oxygen (¹O₂) being transformed from intratumoral oxygen. Nonetheless, the consumption of oxygen during PDT results in serious hypoxic conditions and an elevated hypoxia-inducing factor-1α (HIF-1α) level that hamper further photodynamic efficacy and induce tumor metastasis. To address this problem, we developed hypoxia-assisted NP-co-encapsulating Ce6 (photosensitizer) and YC-1 (HIF-1α inhibitor) as a self-rectifiable nanoinhibitor for synergistic antitumor treatment. PDT-aggravated intracellular hypoxic stress facilitated NP dissociation to release the drug (YC-1), which achieved tumor killing and HIF-1α inhibition to further enhance the therapeutic effect of PDT and prevent tumor metastasis. Besides, <i>in vivo</i> studies revealed that the HC/PI@YC-1 NPs afforded synergistic anticancer efficacy with minimal toxicity. Therefore, this study provides a prospective approach against PDT drawbacks and combination cancer therapy.