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  • Title: Simple and Multifunctional Natural Self-Assembled Sterols with Anticancer Activity-Mediated Supramolecular Photosensitizers for Enhanced Antitumor Photodynamic Therapy.
    Author: Cheng J, Zhao H, Yao L, Li Y, Qi B, Wang J, Yang X.
    Journal: ACS Appl Mater Interfaces; 2019 Aug 21; 11(33):29498-29511. PubMed ID: 31339692.
    Abstract:
    Supramolecular photosensitizers based on nanosized drug delivery or combination therapy have been proposed as a promising strategy for cancer treatment. Herein, we screen and develop a series of multifunctional single-component, carrier-based, natural small-molecule sterols (ergosterol, β-sitosterol, and stigmasterol) that simultaneously possess self-assembly ability, anticancer activity, and better biocompatibility and biodegradability to deliver photosensitizer chlorin e6 (Ce6) for significantly combined and safe antitumor photodynamic therapy. The resultant ergosterol-Ce6 nanodrugs (Ergo-Ce6 NPs) have enhanced reactive oxygen species (ROS) generation by promoting type I photoreactions, while Ce6 mainly exists in the monomer state in assembled Ergo-Ce6 NPs via intermolecular π-π stacking and hydrophobic interactions. In addition, with the improved water solubility and stability and higher intercellular ROS generation, Ergo-Ce6 NPs show remarkably in vitro phototoxicity with approximately 73% and 92% cell inhibition ratios to 4T1 and MCF-7 cancer cells at a rather low dosage of Ce6 (1 μg/mL), respectively. Moreover, the excellent tumor targeting ability of Ergo NPs and prolonged blood circulation ensure a quick tumor accumulation of Ergo-Ce6 NPs, resulting in a significantly enhanced in vivo anticancer efficiency of 86.4%, higher than that of the anticancer ability of Ergo NPs (51.0%) or Ce6 PDT alone (59.5%). Furthermore, the resulting nanodrugs have better biocompatibility and biodegradability and low in vivo toxicity, and all of which ensure a safe tumor therapy. This study provides a promising perspective to develop more natural self-assembled biological small-molecule nanomaterials for the fabrication of novel medicinal photosensitizers for clinical application in the future.
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