Xiangrui Yang1,2,3, Shichao Wu4,5,6, Wanyi Xie1, Anran Cheng1, Lichao Yang1, Zhenqing Hou7, Xin Jin8. 1. Department of Basic Medical Science, Medical College, Xiamen University, Xiamen, 361102, China. 2. Research Center of Biomedical Engineering, College of Materials, Xiamen University, Xiamen, 361005, China. 3. Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China. 4. Department of Basic Medical Science, Medical College, Xiamen University, Xiamen, 361102, China. wushichao@xmu.edu.cn. 5. Research Center of Biomedical Engineering, College of Materials, Xiamen University, Xiamen, 361005, China. wushichao@xmu.edu.cn. 6. Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China. wushichao@xmu.edu.cn. 7. Research Center of Biomedical Engineering, College of Materials, Xiamen University, Xiamen, 361005, China. houzhenqing@xmu.edu.cn. 8. Department of Basic Medical Science, Medical College, Xiamen University, Xiamen, 361102, China. xinjin@xmu.edu.cn.
Abstract
BACKGROUND: Since the anticancer drugs have diverse inhibited mechanisms to the cancer cells, the use of two or more kinds of anticancer agents may achieve excellent therapeutic effects, especially to the drug-resistant tumors. RESULTS: In this study, we developed a kind of dual drug [methotrexate (MTX) and 10-hydroxycamptothecine (HCPT)] loaded nanoneedles (DDNDs) with pronounced targeting property, high drug loading and prolonged drug release. The anti-solvent precipitation of the HCPT and MTX modified PEG-b-PLGA (PEG-b-PLGA-MTX, PPMTX) leads to nucleation of nanoneedles with nanocrystalline HCPT as the core wrapped with PPMTX as steric stabilizers. In vitro cell uptake studies showed that the DDNDs revealed an obviously targeting property and entered the HeLa cells easier than the nanoneedles without MTX modification. The cytotoxicity tests illustrated that the DDNDs possessed better killing ability to HeLa cells than the individual drugs or their mixture in the same dose, indicating its good synergistic effect and targeting property. The in vivo studies further confirmed these conclusions. CONCLUSIONS: This approach led to a promising sustained drug delivery system for cancer diagnosis and treatment.
BACKGROUND: Since the anticancer drugs have diverse inhibited mechanisms to the cancer cells, the use of two or more kinds of anticancer agents may achieve excellent therapeutic effects, especially to the drug-resistant tumors. RESULTS: In this study, we developed a kind of dual drug [methotrexate (MTX) and 10-hydroxycamptothecine (HCPT)] loaded nanoneedles (DDNDs) with pronounced targeting property, high drug loading and prolonged drug release. The anti-solvent precipitation of the HCPT and MTX modified PEG-b-PLGA (PEG-b-PLGA-MTX, PPMTX) leads to nucleation of nanoneedles with nanocrystalline HCPT as the core wrapped with PPMTX as steric stabilizers. In vitro cell uptake studies showed that the DDNDs revealed an obviously targeting property and entered the HeLa cells easier than the nanoneedles without MTX modification. The cytotoxicity tests illustrated that the DDNDs possessed better killing ability to HeLa cells than the individual drugs or their mixture in the same dose, indicating its good synergistic effect and targeting property. The in vivo studies further confirmed these conclusions. CONCLUSIONS: This approach led to a promising sustained drug delivery system for cancer diagnosis and treatment.
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