LAUSR

Supramolecular photosensitizers based on the nano-sized 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-Stiosterol, 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 ROS generation by promoting Type I photoreactions, while Ce6 mainly exists as monomer state in assembled Ergo-Ce6 NPs via intermolecular π-π stacking and hydrophobic interactions. In addition, with the improved water-solubility and stability, higher intercellular ROS generation, Ergo-Ce6 NPs show remarkably in vitro phototoxicity with about 73 % and 92 % cell inhibition ratio to 4T1 and MCF-7 cancer cells at a rather low dosage of Ce6 (1 μg/mL). Moreover, the excellent tumor targeting ability of Ergo NPs and prolonged blood circulation ensures a quick tumor accumulation of Ergo-Ce6 NPs, resulting in significantly in vivo enhanced anticancer efficiency of 86.4 %, higher than the anticancer ability of Ergo NPs (51.0 %) or Ce6 PDT alone (59.5 %). Furthermore, the resulting nanodrugs have better biocompatibility and biodegradability, low in vivo toxicity, all of which ensure a safe tumor therapy. This study provides a promising perspective to develop more natural self-assembled biological small molecules nanomaterials for the fabrication of novel medicinal photosensitizers for clinical application in the future.