Redox responsive liposomal nanohybrid cerasomes for intracellular drug delivery.
Cerasome is a freshly developped bilayer vehicle that resemble traditional liposome but has higher mophorlogical stability. In this study, a novel redox-responsive cerasome (RRC) was developed for tumor-targeting drug delivery. The cerasome-forming lipid (CFL) that comprise a cleavable disulfide bond as connector unit of the triethoxysilyl head and the hydrophobic alkyl double chain was synthesized and subsequently used to prepare cerasome through ethanol injection method. RRC that has liposome-resembling lipid bilayer structure was proved being outstanding at drug loading capacity as well as morphological stability as compared to conventional liposomes. In addition, in vitro drug release tests of DOX/RRCs showed a redox-responsive drug release profile: accelerated DOX releasing compared to reduction-insensitive cerasomes (RICs) in the presence of 10mM of GSH. Under the same condition, the reduction sensibility of RRC was further proved by increased hydrodynamic diameter and destroying of integrity from DLS and SEM results. RRC showed non-toxic to human embryonic kidney 293 cells, indicating that this material has good biocompatibility. On the other hand, DOX/RRCs showed a resemble IC50(half inhibitory concentration) value to that of free DOX to human hepatoma SMMC-7721 cells and breast cancer MCF-7 cells. IC50values at 48h were found to decrease in the following order: DOX/RIC>DOX/RRC>DOX. Taken together, the RRC developped in this study is of great potential to be utilized as a promising platform for intracellular anticancer drug delivery.
School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China; School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Suzhou 215123, China.
Gaoxin
G
Zhou
School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China; School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Suzhou 215123, China; The Center for Vascular and Inflammatory Diseases, University of Maryland, Baltimore, MD 21201, U.S.A, USA.
Lushen
L
Li
School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China; School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Suzhou 215123, China.
Jing
J
Xing
School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China; School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Suzhou 215123, China.
Shivakumar
S
Jalde
School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China; School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Suzhou 215123, China.
Yan
Y
Li
School of Chemistry & Chemical Engineering, Southeast University, Nanjing 210096, China.
Jin
J
Cai
School of Chemistry & Chemical Engineering, Southeast University, Nanjing 210096, China.
Junqing
J
Chen
School of Medicine, Southeast University, Nanjing 210009, China.
Peidang
P
Liu
School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China; School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Suzhou 215123, China. Electronic address: guning@seu.edu.cn.
Ning
N
Gu
School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China; School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Suzhou 215123, China. Electronic address: jimin@seu.edu.cn.
Min
M
Ji
D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D004355:Drug Stability; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D061986:MCF-7 Cells; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010084:Oxidation-Reduction
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008051:Lipid Bilayers; D008081:Liposomes; D004317:Doxorubicin
Cerasome; Doxorubicin; Morphological stability; Redox responsive