Platelets are highly efficient and efficacious carriers for tumor-targeted nano-drug delivery
Qi-Rui Li,
Hua-Zhen Xu,
Rong-Cheng Xiao,
Yan Liu,
Jun-Ming Tang,
Jian Li,
Ting-Ting Yu,
Bin Liu,
Liu-Gen Li,
Mei-Fang Wang,
Ning Han,
Yong-Hong Xu,
Chao Wang,
Naoki Komatsu,
Li Zhao,
Xing-Chun Peng,
Tong-Fei Li,
Xiao Chen
Affiliations
Qi-Rui Li
School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
Hua-Zhen Xu
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, China
Rong-Cheng Xiao
School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
Yan Liu
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, China
Jun-Ming Tang
School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
Jian Li
School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
Ting-Ting Yu
School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
Bin Liu
School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
Liu-Gen Li
School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
Mei-Fang Wang
Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital of Shiyan, Hubei University of Medicine, Shiyan, China
Ning Han
School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
Yong-Hong Xu
Institute of Ophthalmological Research, Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China
Chao Wang
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, China
Naoki Komatsu
Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan
Li Zhao
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China
Xing-Chun Peng
School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
Tong-Fei Li
School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China
Xiao Chen
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, China
The present work aims to prove the concept of tumor-targeted drug delivery mediated by platelets. Doxorubicin (DOX) attached to nanodiamonds (ND-DOX) was investigated as the model payload drug of platelets. In vitro experiments first showed that ND-DOX could be loaded in mouse platelets in a dose-dependent manner with a markedly higher efficiency and capacity than free DOX. ND-DOX-loaded platelets (Plt@ND-DOX) maintained viability and ND-DOX could be stably held in the platelets for at least 4 hr. Next, mouse Lewis lung cancer cells were found to activate Plt@ND-DOX and thereby stimulate cargo unloading of Plt@ND-DOX. The unloaded ND-DOX was taken up by co-cultured cancer cells which consequently exhibited loss of viability, proliferation suppression and apoptosis. In vivo, Plt@ND-DOX displayed significantly prolonged blood circulation time over ND-DOX and DOX in mice, and Lewis tumor grafts demonstrated infiltration, activation and cargo unloading of Plt@ND-DOX in the tumor tissue. Consequently, Plt@ND-DOX effectively reversed the growth of Lewis tumor grafts which exhibited significant inhibition of cell proliferation and apoptosis. Importantly, Plt@ND-DOX displayed a markedly higher therapeutic potency than free DOX but without the severe systemic toxicity associated with DOX. Our findings are concrete proof of platelets as efficient and efficacious carriers for tumor-targeted nano-drug delivery with the following features: 1) large loading capacity and high loading efficiency, 2) good tolerance of cargo drug, 3) stable cargo retention and no cargo unloading in the absence of stimulation, 4) prolonged blood circulation time, and 5) excellent tumor distribution and tumor-activated drug unloading leading to high therapeutic potency and few adverse effects. Platelets hold great potential as efficient and efficacious carriers for tumor-targeted nano-drug delivery.
