Fullerene (C60)-based tumor-targeting nanoparticles with "off-on" state for enhanced treatment of cancer.
The traditional drug delivery systems always suffer from the unexpected drug release during circulation and the sluggish release of drug in target site. To address the problem, an "off-on" type drug delivery system with precise control was developed in this study. Doxorubicin (DOX) was covalently conjugated to fullerene (C60) nanoaggregates via a reactive oxygen species (ROS)-sensitive thioketal linker (C60-DOX NPs), and then the hydrophilic shell (Distearoyl-sn-glycero-3-phosphoethanolamine-PEG-CNGRCK2HK3HK11, DSPE-PEG-NGR) was attached to the outer surface of C60-DOX, giving it (C60-DOX-NGR NP) excellent stability in physiological solutions and active tumor-targeting capacity. C60-DOX-NGR NPs were able to entrap DOX efficiently even at acidic environment (pH5.5) when they were "off" state. In sharp contrast, when the NPs were "on" state, a large number of ROS were generated by C60, leading to the breaking of ROS-sensitive linker, thereby enabling the burst release of DOX. The "off" or "on" state of C60-DOX-NGR NPs could be precisely remote-controlled by a 532nm laser (at a low power density) with a high spatial/temporal resolution. In the in vivo and in vitro studies, the C60-based drug delivery system with "off-on" state exhibited a high antitumor efficacy and a low toxicity to normal tissues due to its tumor-targeting ability, remote-controlled drug release property and combined therapeutic effect (photodynamic therapy combined with chemotherapy).
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China.
Jinjin
J
Shi
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, PR China.
Binghua
B
Wang
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, PR China.
Lei
L
Wang
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, PR China.
Tingting
T
Lu
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, PR China.
Yu
Y
Fu
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, PR China.
Hongling
H
Zhang
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China. Electronic address: zhangzz08@126.com.
Zhenzhong
Z
Zhang
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D037741:Fullerenes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D037741:Fullerenes; D010714:Phosphatidylethanolamines; D017382:Reactive Oxygen Species; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D004317:Doxorubicin; C069837:fullerene C60
Fullerene (C(60)); Nanomedicine; One-demand drug release; Photodynamic-chemotherapy; ROS-manipulated drug release