Cationic polymer synergizing with chemotherapeutics and re-purposing antibiotics against cancer cells
| Autor: | Yi Yan Yang, Jessica Kng, James L. Hedrick, Chuan Yang, Yiran Zheng |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Paclitaxel
Polymers medicine.drug_class medicine.medical_treatment Antibiotics Biomedical Engineering Antineoplastic Agents Drug resistance Pharmacology 010402 general chemistry 01 natural sciences 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Neoplasms medicine General Materials Science Doxorubicin Chemotherapy Chemistry Cancer medicine.disease Anti-Bacterial Agents 0104 chemical sciences 030220 oncology & carcinogenesis Cancer cell Toxicity medicine.drug |
| Zdroj: | Biomaterials Science. 9:2174-2182 |
| ISSN: | 2047-4849 2047-4830 |
| DOI: | 10.1039/d0bm02155e |
| Popis: | Chemotherapy is one of the most effective treatments for cancer. However, toxicity and the development of drug resistance have become the major hurdles to the commonly used chemotherapeutics such as doxorubicin and paclitaxel. Antibiotics have also been used as anti-cancer drugs due to their anti-proliferative and cytotoxic effects. However, these anti-tumor antibiotics like ciprofloxacin face the similar resistance and toxicity issues. In this study, we used a quaternary ammonium-functionalized cationic polycarbonate to synergize with the existing chemotherapeutics and re-purpose antibiotics to address the resistance and toxicity issues. When used in combination with the drugs, the cationic polymer induced 2-3 fold more damage in the cancer cell membrane within 2 hours, thus enhancing the uptake of chemotherapeutics up to 2.5 fold more into the breast, liver and even chemotherapeutics-resistant cancer cells. On the other hand, the chemotherapeutics increased the cellular uptake of polymer. The combined effects resulted in 3-10 fold reduction in IC50 of chemotherapy drugs and yielded therapeutic synergy at a clinically-relevant concentration range of drugs when treating multiple types of cancer cells, while the use of guanidinium-functionalized polymer capable of membrane translocation did not lead to a synergistic effect. Thus, the quaternary ammonium-functionalized cationic polymer can increase the therapeutic efficacies of existing drugs, mitigating toxicities by lowering required dosage and circumventing drug resistance via its membrane disruption mechanism. The findings of this study provide insights into designing future anticancer therapy. |
| Databáze: | OpenAIRE |
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