Peptide coacervates as intracellular delivery vehicles for synergistic cancer photothermal- and chemo-therapies

Intracellular delivery of large molecular weight therapeutics poses a significant challenge in targeted cancer therapy, as conventional delivery vehicles often fail to achieve efficient cellular uptake and controlled release. This study presents a solution using GW26 coacervate microdroplets (CMs), a peptide-based system, as a dual-function platform that not only facilitates the controlled release of therapeutic cargos but also enhances cancer cell death through photothermal therapy (PTT). GW26 CMs exhibit high recruiting efficiency of photothermal (PT) materials—chlorin e6 (Ce6) and gold nanorods—with over 80% efficiency. These CMs demonstrate high cellular uptake in tumor cells, with 98% of CT26 colon carcinoma cells successfully internalizing Ce6-loaded CMs. Upon near-infrared laser irradiation, the PT materials generate localized heat within the therapeutic range for PTT, triggering coacervate disassembly, concomitant cargo release, and death of different human cancer cells, including cervical cancer cells HeLa, colon cancer cells HCT116, and colorectal adenocarcinoma cells HT29. The co-recruitment of the cytotoxic protein saporin enables synergistic PT and chemotherapeutic cancer treatments among all these cells, further enhancing the therapeutic effect, in some cases exhibiting a near-complete loss in cell viability. This approach combines efficient recruitment, controlled cargo release, and enhanced therapeutic efficacy, positioning GW26 CMs as a promising platform for multimodal cancer therapies.