Huang Congxi, Gudlur Sushanth, Maricar Syed, Chen Zilin, Shebanova Anastasia, Sun Yue, Saliba Valentin, Xu Cheng, Zou Yiming, Zhang Jianghong, Boujday Souhir, Miserez Ali
Centre for Sustainable Materials (SusMat), School of Materials Science and Engineering, Nanyang Technological University (NTU), 50 Nanyang Drive, Singapore 637553.
Laboratoire de Réactivité de Surface, Sorbonne Université, 4 Place Jussieu, Paris 75005, France.
APL Bioeng. 2025 Jul 7;9(3):036101. doi: 10.1063/5.0279643. eCollection 2025 Sep.
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.
在靶向癌症治疗中，将大分子量治疗药物递送至细胞内是一项重大挑战，因为传统的递送载体往往无法实现有效的细胞摄取和控释。本研究提出了一种解决方案，即使用GW26凝聚微滴（CMs），这是一种基于肽的系统，作为一种双功能平台，不仅有助于治疗药物的控释，还能通过光热疗法（PTT）增强癌细胞死亡。GW26 CMs对光热（PT）材料——二氢卟吩e6（Ce6）和金纳米棒——具有高效的招募效率，效率超过80%。这些CMs在肿瘤细胞中表现出高细胞摄取率，98%的CT26结肠癌细胞成功内化了负载Ce6的CMs。在近红外激光照射下，PT材料在PTT治疗范围内产生局部热量，触发凝聚层解体，伴随药物释放，并导致不同人类癌细胞死亡，包括宫颈癌细胞HeLa、结肠癌细胞HCT116和结直肠腺癌细胞HT29。细胞毒性蛋白皂草素的共同招募能够在所有这些细胞中实现协同的PT和化疗癌症治疗，进一步增强治疗效果，在某些情况下细胞活力几乎完全丧失。这种方法结合了高效招募、控释药物和增强的治疗效果，使GW26 CMs成为一种有前景的多模态癌症治疗平台。
