Inoue, Satoshi and Ding, Hui and Portilla-Arias, Jose and Hu, Jinwei and Konda, Bindu and Fujita, Manabu and Espinoza, Andres and Riley, Sonal Suhane Marisa and Gates, Marcus and Patil, Rameshwar and Penichet, Manuel L. and Ljubimov, Alexander V. and Black, Keith L. and Holler, Eggehard and Ljubimova, Julia Y. (2011) Polymalic Acid-Based Nanobiopolymer Provides Efficient Systemic Breast Cancer Treatment by Inhibiting both HER2/neu Receptor Synthesis and Activity. CANCER RESEARCH, 71 (4). pp. 1454-1464. ISSN 0008-5472,
Full text not available from this repository. (Request a copy)Abstract
Biodegradable nanopolymers are believed to offer great potential in cancer therapy. Here, we report the characterization of a novel, targeted, nanobiopolymeric conjugate based on biodegradable, nontoxic, and nonimmunogenic PMLA [poly(beta-L-malic acid)]. The PMLA nanoplatform was synthesized for repetitive systemic treatments of HER2/neu-positive human breast tumors in a xenogeneic mouse model. Various moieties were covalently attached to PMLA, including a combination of morpholino antisense oligonucleotides (AON) directed against HER2/neu mRNA, to block new HER2/neu receptor synthesis; anti-HER2/neu antibody trastuzumab (Herceptin), to target breast cancer cells and inhibit receptor activity simultaneously; and transferrin receptor antibody, to target the tumor vasculature and mediate delivery of the nanobiopolymer through the host endothelial system. The results of the study showed that the lead drug tested significantly inhibited the growth of HER2/neu-positive breast cancer cells in vitro and in vivo by enhanced apoptosis and inhibition of HER2/neu receptor signaling with suppression of Akt phosphorylation. In vivo imaging analysis and confocal microscopy demonstrated selective accumulation of the nanodrug in tumor cells via an active delivery mechanism. Systemic treatment of human breast tumor-bearing nude mice resulted in more than 90% inhibition of tumor growth and tumor regression, as compared with partial (50%) tumor growth inhibition in mice treated with trastuzumab or AON, either free or attached to PMLA. Our findings offer a preclinical proof of concept for use of the PMLA nanoplatform for combination cancer therapy. Cancer Res; 71(4); 1454-64. (c) 2011 AACR.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DRUG-DELIVERY; TRASTUZUMAB RESISTANCE; DOWN-REGULATION; TUMOR GROWTH; PHASE-II; CELLS; CHEMOTHERAPY; EXPRESSION; HERCEPTIN; APOPTOSIS; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Jun 2020 13:04 |
| Last Modified: | 25 Jun 2020 13:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21263 |
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