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A Self-Assembling Janus Dendron-Modified Phthalocyanine Enables Deep Tumor-Targeted Therapy for Gastric Cancer Peritoneal Metastases.

Created on 08 Sep 2026

Authors

Jianping Guo, Shujie Zhang, Zijian Deng, Guantao He, Yiming Guo, Longyang Jin, Di Zhang, Keqian Du, Zhizhong Xiong, Shi Yin, Saddam Ahmed Mohamed, Lin-Ping Wu, Lei Lian

Published in

Advanced healthcare materials. Pages e71702. Sep 07, 2026. Epub Sep 07, 2026.

Abstract

Peritoneal metastasis is a leading cause of mortality in end-stage gastric cancer and remains poorly responsive to conventional chemotherapy. To address this unmet need, Janus dendron-modified phthalocyanines were developed as tumor-targeted photosensitizers for photodynamic therapy (PDT). A series of Janus dendron-modified phthalocyanines with tailored surface functionalities s synthesized, exhibiting spontaneous self-assembly into nanoparticles with augmented fluorescence, amplified reactive oxygen species (ROS) production, and improved tumor-targeting specificity. Among them, the lead compound TT1-4PYR, bearing pyrrolidone moieties, demonstrated ascites-derived protein corona and macropinocytosis-mediated cellular internalization, enabling deep penetration and selective accumulation in peritoneal metastasis lesions. Comprehensive evaluation in vitro, in vivo, and in human-derived gastric cancer organoid models confirmed its potent and targeted photodynamic cytotoxicity, effectively suppressing tumor progression without inducing systemic toxicity, achieving a favorable biosafety profile. These results highlight TT1-4PYR as a promising and deep-penetrating therapeutic agent for peritoneal metastasis, with potential applicability to other metastatic malignancies.

PMID:
42706771
Bibliographic data and abstract were imported from PubMed on 08 Sep 2026.

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