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. (26th November 2021)

• Record Type: Journal Article
• Authors: Chen, Michael; Sheu, Ming-Thau; Cheng, Tian-Lu; Roffler, Steve R.; Lin, Shyr-Yi; Chen, Yi-Jou; Cheng, Yi-An; Cheng, Jing-Jy; Chang, Hsin-Yu; Wu, Tung-Yun; Kao, An-Pei; Ho, Yuan-Soon; Chuang, Kuo-Hsiang
• Is Part Of: Biomaterials science. Volume 10:Number 1(2022)
• Page Start: 202
• Page End: 215
• Publication Date: 2021-11-26
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d1bm01218e
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : Clinical nanoparticles were armed with TsAb through a one-step non-covalent modification to achieve the maximal specific killing against TAF-rich solid tumors. 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.