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F3-functionalized nanoscale metal–organic frameworks for tumor-targeting combined chemotherapy and chemodynamic therapy |
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| Authors: | Jia Liu Yiyang Cong Yawen Zeng Yiming He Ying Luo Weifei Lu Haixing Xu Yihua Yin Hao Hong Wenjin Xu |
| Affiliation: | 1. Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, Hubei, China;2. Medical School of Nanjing University, Nanjing, Jiangsu, China
Contribution: Methodology (lead);3. Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, Hubei, China Contribution: Formal analysis (lead);4. Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, Hubei, China Contribution: Investigation (lead);5. College of Veterinary Medicine, Henan Agricultura University, Zhengzhou, Henan, China Contribution: Methodology (lead);6. Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, Hubei, China Contribution: Funding acquisition (lead);7. Medical School of Nanjing University, Nanjing, Jiangsu, China |
| Abstract: | Nanoscale metal–organic frameworks (nMOFs) have attracted much attention as emerging porous materials as drug delivery carriers. Appropriate surface modification of them can greatly improve stability and introduce biocompatibility and cancer targeting functionality into drug delivery systems. Herein, we prepared nano-sized MIL-101(Fe)-N3 and loaded anticancer drug doxorubicin (DOX) into it. The synthetic polymer layer Alkyne-PLA-PEG was then attached to the F3 peptide (labeled as Alkyne-PLA-PEG-F3), and the surface of DOX/MIL-101(Fe)-N3 was covalently modified with it to obtain DOX/MIL-101-PLA-PEG-F3. Nano-sized MIL-101(Fe)-N3 has high drug loading capacity and the modification of MIL-101(Fe)-N3 by polymer Alkyne-PLA-PEG not only improved the dispersion, but also avoided the sudden release of the drugs and increased the biocompatibility of nanocarriers. The F3 peptide introduced into the nanocarriers also enabled it to specifically target tumor tissues and achieved active targeted drug delivery. As a nucleolin-mediated endocytosis drug delivery system, DOX/MIL-101-PLA-PEG-F3 can not only deliver anticancer drugs to tumors accurately, but also participate in Fenton-like reaction to generate hydroxyl radicals (•OH) for chemodynamic therapy (CDT), thus enabling combination therapy. It holds great promise as drug candidates to reduce systemic toxicity and improve the efficacy of cancer treatment. |
| Keywords: | cancer targeting chemodynamic therapy click chemistry drug delivery system nanoscale metal-organic frameworks |