A novel anti-tumor/anti-tumor-associated fibroblast/anti-mPEG tri-specific antibody to maximize the efficacy of mPEGylated nanomedicines against fibroblast-rich solid tumor

Michael Chen, Ming Thau Sheu, Tian Lu Cheng, Steve R. Roffler, Shyr Yi Lin, Yi Jou Chen, Yi An Cheng, Jing Jy Cheng, Hsin Yu Chang, Tung Yun Wu, An Pei Kao, Yuan Soon Ho, Kuo Hsiang Chuang

Research output: Contribution to journalArticlepeer-review

Abstract

The therapeutic efficacy of methoxypolyethylene glycol (mPEG)-coated nanomedicines in solid tumor treatment is hindered by tumor-associated fibroblasts (TAFs), which promote tumor progression and form physical barriers. We developed an anti-HER2/anti-FAP/anti-mPEG tri-specific antibody (TsAb) for one-step conversion of mPEG-coated liposomal doxorubicin (Lipo-Dox) to immunoliposomes, which simultaneously target HER2+ breast cancer cells and FAP+ TAFs. The non-covalent modification did not adversely alter the physical characteristics and stability of Lipo-Dox. The TsAb-Lipo-Dox exhibited specific targeting and enhanced cytotoxicity against mono- and co-cultured HER2+ breast cancer cells and FAP+ TAFs, compared to bi-specific antibody (BsAb) modified or unmodified Lipo-Dox. An in vivo model of human breast tumor containing TAFs also revealed the improved tumor accumulation and therapeutic efficacy of TsAb-modified mPEGylated liposomes without signs of toxicity. Our data indicate that arming clinical mPEGylated nanomedicines with the TsAb is a feasible and applicable approach for overcoming the difficulties caused by TAFs in solid tumor treatment.

Original languageEnglish
Pages (from-to)202-215
Number of pages14
JournalBiomaterials Science
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 7 2022

ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)

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