Abstract
Background: Photodynamic therapy (PDT) has been recognized as a promising tumor treatment for its minimal invasiveness, low side effects and on-demand light controllability. However, the oxygen-dependent PDT could exacerbate tumor hypoxia to upregulate the expression of hypoxia-inducible factor-1α (HIF-1α), which would promote tumor growth and metastasis. Inhibition of HIF-1α activity is very necessary to PDT for effective tumor suppression.Results: Herein, we developed a self-remedied nanomedicine based on a photosensitizer and a HIF-1α inhibitor to surmount the Achilles' heel of PDT for enhanced antitumor efficacy. Specifically, the nanomedicine (designated as CYC-1) was prepared by the self-assembly of Ce6 and YC-1 through π-π stacking and hydrophobic interactions. Carrier-free CYC-1 held an extremely high drug loading rate, uniform size distribution and favorable stability. Compared with free Ce6, CYC-1 exhibited an improved cellular uptake behavior and an enhanced ROS production capability. Besides, CYC-1 had the overwhelming superiority on restraining tumor proliferation over the combined administration of Ce6 and YC-1. More importantly, CYC-1 preferred to accumulate in tumor tissue for efficient PDT by inhibiting the activity of HIF-1α. Ultimately, this YC-1-assistant PDT effectively restrained the tumor growth and caused a low system toxicity. Conclusions: This carrier-free self-remedied strategy overcame the Achilles' heel of PDT on tumor suppression while induced a minimal side effect, which would expedite the development and clinical translation of nanomedicine for PDT against hypoxic tumors.
new bIologIcal model of moderate InhIbItIon of tumor and metastases growth wIth prolonged leukopenIa In mIce
