Self-Remedied Nanomedicine for Surmounting the Achilles’ Heel of Photodynamic Tumor Therapy

Abstract

Oxygen-dependent photodynamic therapy (PDT) could exacerbate tumor hypoxia to induce the upregulation of hypoxia-inducible factor-1α (HIF-1α), which would promote tumor growth and metastasis. In this paper, a self-remedied nanomedicine is developed 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) is prepared by the self-assembly of chlorine e6 (Ce6) and 3-(5′-hydroxy-methyl-2′-furyl)-1-benzylindazole (YC-1) through π−π stacking and hydrophobic interactions. Of special note, carrier-free CYC-1 holds an extremely high drug loading rate and avoids excipienttriggered adverse reactions. Intravenously administered CYC-1 prefers to accumulate in the tumor tissue for effective cellular uptake. More importantly, it is verified that CYC-1 is capable of inhibiting the HIF-1α activity, thereby improving its PDT efficacy on tumor suppression. Besides, CYC-1 has the overwhelming superiority in restraining tumor proliferation over the combined administration of Ce6 and YC-1, which highlights the advantage of this self-remedied strategy in drug delivery and tumor therapy. This study sheds light on the development of self-delivery nanomedicine for efficient PDT against malignancies.

Paraptosis Inducer to Effectively Trigger Immunogenic Cell Death for Metastatic Tumor Immunotherapy with IDO Inhibition

“…Moreover, the biosafety of various drug carriers gets more and more attentions, and a preferred strategy is to deliver drugs by themselves. Recently, some drug molecules are found to self-assemble into nanomedicine without extra drug excipients, which can also improve the drug stability and delivery efficiency. − Even so, the structure and the pharmacological behavior of drugs vary tremendously, which greatly affects their assembly behaviors and synergistic effects. Therefore, the self-delivery nanomedicine of morusin and IDO inhibitor is urgently needed but rarely reported for systemic tumor treatment.…”