期刊
BIOMATERIALS SCIENCE
卷 10, 期 1, 页码 202-215出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1bm01218e
关键词
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资金
- Ministry of Science and Technology, Taiwan [MOST 110-2320-B-038-030, 110-2628-B-038-011, MOST 106-2632-B-038-001]
- National Health Research Institutes, Taiwan [NHRI-EX110-10935SI]
- Jin-lung-Yuan Foundation
- Ministry of Education [RSC 110-5804-002-400]
- Health and Welfare Surcharge of Tobacco Products, Taiwan [MOHW110-TDU-B-212-144014]
The development of an anti-HER2/anti-FAP/anti-mPEG tri-specific antibody (TsAb) for converting mPEG-coated liposomal doxorubicin to immunoliposomes shows improved tumor accumulation and therapeutic efficacy, overcoming the challenges posed by TAFs in solid tumor treatment. The TsAb-modified mPEGylated liposomes exhibit specific targeting and enhanced cytotoxicity against both HER2(+) breast cancer cells and FAP(+) TAFs.
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.
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