Fabrication of modular multifunctional delivery for antitumor drugs based on host-guest recognition.
Herein, learning from the idea of the modular concept widely used in ship building, as a design approach that assembles some subdivided smaller modules to a specific ship, a new modular multifunctional drug delivery (MMDD) with excellent biocompatibility was directly prepared by a flexible host-guest interaction between pH-sensitive benzimidazole-graft-dextran (Dex-BM) and pre-synthesized multifunctional cyclodextrins. In this drug system, pH-sensitive Dex-BM acted as the main case and pre-synthesized multifunctional cyclodextrins were the changeable modules. To verify the feasibility of MMDD in cancer chemotherapy, doxorubicin (DOX) was used as a model drug. In vitro drug release experiments indicated that the drug released around 80% from DOX-loaded MMDD at pH 5.3, while approximately 40% of DOX released under the condition of pH 7.4. Moreover, the targeting antitumor activity of DOX-loaded MMDD was investigated in HeLa and HepG2 cells using MTT assays, confocal laser scanning microscopy and flow cytometer, which indicated that the targeted DOX-loaded MMDD provided an efficient drug delivery platform for inhibition of different cancer cells. Meantime, the incorporation of different functional modules into one system was also investigated, simultaneously exhibiting targeting and imaging property. These features suggest that this modular multifunctional drug delivery system can efficiently enhance the inhibition of cellular proliferation in vitro, and according to the needs in clinical treatment, some targeting and imaging molecules can be chosen.
Department of Chemistry, Northeast Normal University, Changchun 130024, PR China. Electronic address: chenl686@nenu.edu.cn.
Li
L
Chen
Department of Chemistry, Northeast Normal University, Changchun 130024, PR China.
Zhe
Z
Zhang
Department of Chemistry, Northeast Normal University, Changchun 130024, PR China.
Xiaofei
X
Chen
Department of Chemistry, Northeast Normal University, Changchun 130024, PR China.
Xuemei
X
Yao
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
Chaoliang
C
He
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address: xschen@ciac.ac.cn.
Xuesi
X
Chen
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry; D004187:Disaccharides / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008823:Micelles; D066244:Proton Magnetic Resonance Spectroscopy; D013050:Spectrometry, Fluorescence; D047392:beta-Cyclodextrins / Q000737:chemistry
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D003911:Dextrans; D004187:Disaccharides; D008823:Micelles; D047392:beta-Cyclodextrins; C005608:lactobionic acid; D004317:Doxorubicin; D005492:Folic Acid; C031000:benzimidazole; D016650:Fluorescein-5-isothiocyanate; C031215:betadex
Benzimidazole-graft-dextran; Doxorubicin; Modular multifunctional drug delivery; Multifunctional cyclodextrins; Tumor therapy