Π electron-stabilized polymeric micelles potentiate docetaxel therapy in advanced-stage gastrointestinal cancer

Chenghua Liang, Xiangyang Bai, Cuiling Qi, Qingxue Sun, Xiaoyan Han, Tianyun Lan, Haibo Zhang, Xiaoming Zheng, Rongpu Liang, Ju Jiao, Zongheng Zheng, Jiafeng Fang, Purun Lei, Yan Wang, Diana Möckel, Josbert M. Metselaar, Gert Storm, Wim E. Hennink, Fabian Kiessling, Hongbo Wei*Twan Lammers, Yang Shi, Bo Wei

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

Abstract

Gastrointestinal (GI) cancers are among the most lethal malignancies. The treatment of advanced-stage GI cancer involves standard chemotherapeutic drugs, such as docetaxel, as well as targeted therapeutics and immunomodulatory agents, all of which are only moderately effective. We here show that Π electron-stabilized polymeric micelles based on PEG-b-p(HPMAm-Bz) can be loaded highly efficiently with docetaxel (loading capacity up to 23 wt%) and potentiate chemotherapy responses in multiple advanced-stage GI cancer mouse models. Complete cures and full tumor regression were achieved upon intravenously administering micellar docetaxel in subcutaneous gastric cancer cell line-derived xenografts (CDX), as well as in CDX models with intraperitoneal and lung metastases. Nanoformulated docetaxel also outperformed conventional docetaxel in a patient-derived xenograft (PDX) model, doubling the extent of tumor growth inhibition. Furthermore, micellar docetaxel modulated the tumor immune microenvironment in CDX and PDX tumors, increasing the ratio between M1-and M2-like macrophages, and toxicologically, it was found to be very well-tolerated. These findings demonstrate that Π electron-stabilized polymeric micelles loaded with docetaxel hold significant potential for the treatment of advanced-stage GI cancers.

Original languageEnglish
Article number120432
JournalBiomaterials
Volume266
DOIs
Publication statusPublished - Jan 2021

Keywords

  • Gastrointestinal cancer
  • Nanomedicine
  • Polymeric micelles
  • Taxane therapy
  • Tumor microenvironment
  • Tumor targeting

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