Synthesis and Evaluation of Doxorubicin-Loaded Gold Nanoparticles for Tumor-Targeted Drug Delivery
| Autor: | Long Xia, Marion Ehrich, David G. I. Kingston, Richey M. Davis, Yongle Du, Ami Jo, Philippe Bissel |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Drug Side effect media_common.quotation_subject Biomedical Engineering Metal Nanoparticles Pharmaceutical Science Nanoparticle Bioengineering 02 engineering and technology Pharmacology 010402 general chemistry 01 natural sciences Mice Drug Delivery Systems Cell Line Tumor Neoplasms PEG ratio polycyclic compounds medicine Animals Humans Doxorubicin Cell Proliferation media_common Drug Carriers Cardiotoxicity Antibiotics Antineoplastic Chemistry Organic Chemistry 021001 nanoscience & nanotechnology 0104 chemical sciences Colloidal gold Drug delivery Gold 0210 nano-technology Biotechnology medicine.drug |
| Zdroj: | Bioconjugate Chemistry. 29:420-430 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/acs.bioconjchem.7b00756 |
| Popis: | Doxorubicin is an effective and widely used cancer chemotherapeutic agent, but its application is greatly compromised by its cumulative dose-dependent side effect of cardiotoxicity. A gold nanoparticle-based drug delivery system has been designed to overcome this limitation. Five novel thiolated doxorubicin analogs were synthesized and their biological activities evaluated. Two of these analogs and PEG stabilizing ligands were then conjugated to gold nanoparticles, and the resulting Au-Dox constructs were evaluated. The results show that release of native drug can be achieved by the action of reducing agents such as glutathione or under acidic conditions, but reductive drug release gave the cleanest drug release. Gold nanoparticles (Au-Dox) were prepared with different loadings of PEG and doxorubicin, and one formulation was evaluated for mammalian stability and toxicity. Plasma levels of doxorubicin in mice treated with Au-Dox were significantly lower than in mice treated with the same amount of doxorubicin, indicating that the construct is stable under physiological conditions. Treatment of mice with Au-Dox gave no histopathologically observable differences from mice treated with saline, while mice treated with an equivalent dose of doxorubicin showed significant histopathologically observable lesions. |
| Databáze: | OpenAIRE |
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