Patil, Rameshwar and Portilla-Arias, Jose and Ding, Hui and Inoue, Satoshi and Konda, Bindu and Hu, Jinwei and Wawrowsky, Kolja A. and Shin, Paul K. and Black, Keith L. and Holler, Eggehard and Ljubimova, Julia Y. (2010) Temozolomide Delivery to Tumor Cells by a Multifunctional Nano Vehicle Based on Poly(beta-L-malic acid). PHARMACEUTICAL RESEARCH, 27 (11). pp. 2317-2329. ISSN 0724-8741,
Full text not available from this repository. (Request a copy)Abstract
Temozolomide (TMZ) is a pro-drug releasing a DNA alkylating agent that is the most effective drug to treat glial tumors when combined with radiation. TMZ is toxic, and therapeutic dosages are limited by severe side effects. Targeted delivery is thus needed to improve efficiency and reduce non-tumor tissue toxicity. Multifunctional targetable nanoconjugates of TMZ hydrazide were synthesized using poly(beta-L-malic acid) platform, which contained a targeting monoclonal antibody to transferrin receptor (TfR), trileucine (LLL), for pH-dependent endosomal membrane disruption, and PEG for protection. The water-soluble TMZ nanoconjugates had hydrodynamic diameters in the range of 6.5 to 14.8 nm and zeta potentials in the range of -6.3 to -17.7 mV. Fifty percent degradation in human plasma was observed in 40 h at 37A degrees C. TMZ conjugated with polymer had a half-life of 5-7 h, compared with 1.8 h for free TMZ. The strongest reduction of human brain and breast cancer cell viability was obtained by versions of TMZ nanoconjugates containing LLL and anti-TfR antibody. TMZ-resistant cancer cell lines were sensitive to TMZ nanoconjugate treatment. TMZ-polymer nanoconjugates entered the tumor cells by receptor-mediated endocytosis, effectively reduced cancer cell viability, and can potentially be used for targeted tumor treatment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DRUG-DELIVERY; CANCER-CHEMOTHERAPY; MALIGNANT GLIOMA; SOLID TUMOR; GLIOBLASTOMA; THERAPEUTICS; PERMEABILITY; EXPRESSION; ANTIBODIES; RESISTANCE; anti-TfR mAb; nanoconjugate; pH-dependent membrane disruption; polymalic acid; targeted drug delivery; temozolomide |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Jul 2020 05:03 |
| Last Modified: | 08 Jul 2020 05:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/23980 |
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