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Nanotoxicology of an Elastin-like Polypeptide Rapamycin Formulation for Breast Cancer.
- Source :
-
Biomacromolecules [Biomacromolecules] 2020 Mar 09; Vol. 21 (3), pp. 1091-1102. Date of Electronic Publication: 2020 Feb 06. - Publication Year :
- 2020
-
Abstract
- The clinical utility of rapamycin (Rapa) is limited by solubility, bioavailability, and side effects. To overcome this, our team recently reported an elastin-like polypeptide (ELP) nanoparticle with high affinity, noncovalent drug binding, and integrin-mediated cellular uptake. Given the scarcity of pharmacology/toxicology studies of ELP-based drug carriers, this article explores safety and efficacy of ELP-Rapa. ELP-Rapa nanoparticles tested negative for hemolysis, did not interfere in plasma coagulation nor in platelet function, and did not activate the complement. Upon incubation with HepG2 cells, ELP-Rapa revealed significant cellular uptake and trafficking to acidic organelles, consistent with lysosomes. Internalized ELP-Rapa nanoparticles increased oxidative stress 4-fold compared to free drug or free ELP controls. However, mice bearing orthotopic hormone receptor positive BT-474 breast tumors, given a high dose (∼10-fold above therapeutic dose) of 1 month administration of ELP-Rapa, did not induce hepatotoxicity. On the other hand, tumor growth and mTOR signaling were suppressed without affecting body weight. Nanoparticles assembled using ELP technology appear to be a safe and efficient strategy for delivering Rapa.
Details
- Language :
- English
- ISSN :
- 1526-4602
- Volume :
- 21
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biomacromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 31927993
- Full Text :
- https://doi.org/10.1021/acs.biomac.9b01431