Enhancement of tumor tropism of mPEGylated nanoparticles by anti-mPEG bispecific antibody for ovarian cancer therapy
| Autor: | Chia-Ching Li, Chiu-Min Cheng, Yun-Chi Lu, Hung-Wen Lai, Kai-Wen Ho, I-Ju Chen, Yi-An Cheng, Ming-Yii Huang, Huei-Jen Chen, Hui-Ju Liu, Bo-Cheng Huang, Wen-Wei Lin, Tian-Lu Cheng |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Bispecific antibody Cancer therapy Science Endocytosis Tropism Article Polyethylene Glycols 03 medical and health sciences Ovarian tumor Mice 0302 clinical medicine Drug Delivery Systems Cell Line Tumor Antibodies Bispecific medicine Animals Humans Cytotoxicity skin and connective tissue diseases neoplasms Cancer Ovarian Neoplasms Drug Carriers Mice Inbred BALB C Multidisciplinary business.industry Tumor tropism medicine.disease 030104 developmental biology Doxorubicin 030220 oncology & carcinogenesis Toxicity Cancer cell Cancer research MCF-7 Cells Nanoparticles Medicine Cancer imaging Female lipids (amino acids peptides and proteins) Neoplasm Recurrence Local Ovarian cancer business |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Ovarian cancer is highly metastatic, with a high frequency of relapse, and is the most fatal gynecologic malignancy in women worldwide. It is important to elevate the drug susceptibility and cytotoxicity of ovarian cancer cells, thereby eliminating resident cancer cells for more effective therapeutic efficacy. Here, we developed a bispecific antibody (BsAb; mPEG × HER2) that can easily provide HER2+ tumor tropism to mPEGylated liposomal doxorubicin (PLD) and further increase the drug accumulation in cancer cells via receptor-mediated endocytosis, and improve the cytotoxicity and therapeutic efficacy of HER2+ ovarian tumors. The mPEG × HER2 can simultaneously bind to mPEG molecules on the surface of PLD and HER2 antigen on the surface of ovarian cancer cells. Simply mixing the mPEG × HER2 with PLD was able to confer HER2 specificity of PLD to HER2+ ovarian cancer cells and efficiently trigger endocytosis and enhance cytotoxicity by 5.4-fold as compared to non-targeted PLD. mPEG × HER2-modified PLD was able to significantly increase the targeting and accumulation of HER2+ ovarian tumor by 220% as compared with non-targeted PLD. It could also significantly improve the anti-tumor activity of PLD (P |
| Databáze: | OpenAIRE |
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