Exploring the heat-triggered release of cancer cell-killing cargo

Traditional drug delivery vehicles fail to efficiently deliver and release cancer therapeutics of large molecular weight to tumor cells. To overcome this, Huang et al. are turning to GW26 coacervate microdroplets (CMs) as a drug delivery platform. This peptide-based system features low toxicity and a simple structure, is readily taken up by cells, and efficiently recruits therapeutics with a wide range of molecular weights.

The authors investigated using heat to control the release of therapeutic cargoes from GW26 CMs. The heat is generated by photothermal materials that convert light into heat. The authors found GW26 CMs were able to separately recruit two photothermal cargoes, chlorin e6 and gold nanorods, efficiently while demonstrating a high uptake in tumor cells. When they applied laser light, the heat from the photothermal materials disassembled the GW26s CMs and released the recruited cargoes. The heat also decreased the viability of the cancer cells.

With either gold nanorods or chlorin e6, GW26 CMs were able to co-recruit a third cargo: saporin. When this cytotoxin was released along with a photothermal material, it further decreased the viability of the cancer cells. These results suggest GW26 CMs are a promising multifunctional delivery system for both photothermal and chemotherapeutic cancer treatments.

“Our research shows that GW26 CMs can be an efficient, targeted, and multimodal drug delivery and release platform for synergistic cancer therapy,” said author Congxi Huang. “We pave the way for using GW26 CMs as a heat-induced targeted drug release platform for cancer therapeutics.”

But before this heat-triggered drug delivery system can be applied at a large scale, researchers will need to study its performance in animals and with more cargoes.

Source: “Peptide coacervates as intracellular delivery vehicles for synergistic cancer photothermal- and chemo- therapies,” by Congxi Huang, Sushanth Gudlur, Syed Maricar, Zilin Chen, Anastasia Shebanova, Yue Sun, Valentin Saliba, Cheng Xu, Yiming Zou, Jianghong Zhang, Souhir Boujday, and Ali Miserez, APL Bioengineering (2025). The article can be accessed at https://doi.org/10.1063/5.0279643 .