Hydrogen Sulfide Triggered Charge-Reversal Micelles for Cancer-Targeted Drug Delivery and Imaging.
Currently, the development of polymeric micelles combining diagnosis and targeted therapy is theoretically and practically significant in cancer treatment. In addition, it has been reported that cancer cells can produce large amounts of hydrogen sulfide (H2S) and their survival depends on the content of H2S. In this study, a series of N-(2-hydroxyethyl)-4-azide-1,8-naphthalimide ended amphiphilic diblock copolymer poly(2-hydroxyethyl methacrylate)-block-poly(methyl methacrylate) (N3-Nap-PHEMA-b-PMMA-N3) micelles were prepared. Around cancer tissues, the N3-Nap-PHEMA45-b-PMMA42-N3 micelles exhibited dual characteristics of monitoring H2S and H2S triggered charge reversal with the reduction of the azido group. The surface charge of N3-Nap-PHEMA45-b-PMMA42-N3 micelles reversed from negative to positive after monitoring H2S. With H2S triggered charge reversal, the cellular uptake of DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles was effectively enhanced through electrostatic attraction mediated targeting, and a fast doxorubicin (DOX) release rate was observed. The MTT assay demonstrated that N3-Nap-PHEMA45-b-PMMA42-N3 micelles were biocompatible to HeLa cells, and DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles showed enhanced cytotoxicity in HeLa cells in the presence of H2S. Furthermore, in vivo fluorescence imaging and biodistribution experiments revealed that DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles could provide good tumor imaging and accumulate in tumor tissue. Therefore, N3-Nap-PHEMA45-b-PMMA42-N3 micelles can be used as a promising platform for tumor diagnosis and therapy.
Institute of Fluorescent Probes for Biological Imaging, School of Chemistry and Chemical Engineering, School of Biological Science and Technology, University of Jinan , Jinan, Shandong 250022, People's Republic of China.
Haitao
H
Zhang
Institute of Fluorescent Probes for Biological Imaging, School of Chemistry and Chemical Engineering, School of Biological Science and Technology, University of Jinan , Jinan, Shandong 250022, People's Republic of China.
Xiuqi
X
Kong
Institute of Fluorescent Probes for Biological Imaging, School of Chemistry and Chemical Engineering, School of Biological Science and Technology, University of Jinan , Jinan, Shandong 250022, People's Republic of China.
Yonghe
Y
Tang
Institute of Fluorescent Probes for Biological Imaging, School of Chemistry and Chemical Engineering, School of Biological Science and Technology, University of Jinan , Jinan, Shandong 250022, People's Republic of China.
Weiying
W
Lin
D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D011092:Polyethylene Glycols; D014018:Tissue Distribution
D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; D004317:Doxorubicin; D006862:Hydrogen Sulfide
cancer imaging; charge-reversal; fluorescent probes; hydrogen sulfide; micelles; targeted drug delivery