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Tytuł:
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Zwitterionic nanoparticles constructed with well-defined reduction-responsive shell and pH-sensitive core for "spatiotemporally pinpointed" drug delivery.
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Autorzy:
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Huang P; Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.
Liu J
Wang W
Li C
Zhou J
Wang X
Deng L
Kong D
Liu J
Dong A
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Źródło:
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ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2014 Aug 27; Vol. 6 (16), pp. 14631-43. Date of Electronic Publication: 2014 Aug 13.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Washington, D.C. : American Chemical Society
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MeSH Terms:
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Doxorubicin/*chemistry
Drug Carriers/*chemistry
Drug Delivery Systems/*methods
Nanoparticles/*chemistry
Animals ; Doxorubicin/administration & dosage ; Female ; HeLa Cells ; Hep G2 Cells ; Humans ; Hydrogen-Ion Concentration ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays
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Substance Nomenclature:
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0 (Drug Carriers)
80168379AG (Doxorubicin)
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Entry Date(s):
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Date Created: 20140808 Date Completed: 20151207 Latest Revision: 20140827
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Update Code:
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20240104
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DOI:
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10.1021/am503974y
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PMID:
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25100635
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Enabling nanocarriers to complete the sophisticated journey from the initial injection site to the targeted tumor cells and achieve "spatiotemporally pinpointed" drug release intracellularly is a challenging task in anticancer drug delivery. Herein, versatile shell-cross-linked nanoparticles (SCNPs) were prepared by one-step assembly of triblock zwitterionic copolymers, polycarboxybetaine methacrylate-block-poly(N-(2-(2-pyridyl disulde) ethyl methacrylamide-block-poly(2-(diisopropylamino) ethyl methacrylate) (PCB-b-PDS-b-PDPA, termed as PCSSD), which was well-defined via reversible additive fragment transfer (RAFT) polymerization, followed by functionalization with Arg-Gly-Asp (RGD). Thus, the RGD-PCSSD SCNPs cooperatively combine the ultra pH-sensitive PDPA core for efficient drug loading and pH-responsive drug release, the disulfide-cross-linked PDS shell that prevents premature drug release, the zwitterionic PCB corona to stabilize the SCNPs and prolong its systemic circulation, the RGD ligand for active tumor targeting and receptor-mediated endocytosis. Doxorubicin (DOX) was loaded as a model medicine (termed as RGD-PCSSD/DOX SCNPs). The dual-sensitivity studies showed that the pH-sensitivity of PDPA core could be adjusted by the shell-cross-linking density, accompanied by better control over premature drug release. Furthermore, results obtained by flow cytometry and fluorescence microscopy analysis demonstrated that once the RGD-PCSS10D/DOX SCNPs were internalized into tumor cells via receptor-mediated endocytosis, boost drug release was observed with considerable cytotoxicity in vitro. The results of ex vivo imaging studies further confirmed the successful drug delivery from the injection site to the tumor tissue. In summary, the well-constructed RGD-PCSS10D/DOX SCNPs with cooperative multifunctionality showed great potential as novel nanocarriers for tumor targeted anticancer drug delivery.
