A metal-coordination stabilized small-molecule nanomedicine with high drug-loading capacity and synergistic photochemo-therapy for cancer treatments

Abstract

Conventional nanomedicines typically employ a significant amount of excipients as carriers for therapeutic delivery, resulting in generally low drug-loading and compromised anti-cancer efficacy. Here, we propose a small-molecule nanomedicine (CMC NP) directly assembled by chemotherapeutic drug (chlorambucil, CBL) and phototherapeutic agents (chlorin e6, Ce6), and stabilized by metal coordination. The CMC NPs exhibit exceptionally high drug loading (89.21%), robust stability, and smart disassembly in response to glutathione (GSH). Such a straightforward yet multifunctional delivery strategy could be a better alternative to overcome above shortcomings of conventional nanomedicine while achieving enhanced efficacy. The CMC NP not only directly induces CBL-induced chemotherapy but also elicits synergistic antitumor responses through Ce6-mediated photodynamic and photothermal therapies. Owing to the mul-tifaceted efforts from photodynamic, photothermal and chemo therapies, the CMC NP exhibits excellent antitumor efficacy with negligible systemic toxicity that is untenable in traditional CBL-induced chemotherapy. Therefore, this study provides a feasible strategy for overcoming existing challenges and presenting a potential opportunity to augment the clinical therapeutic ef-fectiveness of associated with conventional nanomedicine.