PMID- 35999612
OWN - NLM
STAT- MEDLINE
DCOM- 20220825
LR  - 20231213
IS  - 1477-3155 (Electronic)
IS  - 1477-3155 (Linking)
VI  - 20
IP  - 1
DP  - 2022 Aug 23
TI  - alphavbeta3 integrin-specific exosomes engineered with cyclopeptide for targeted 
      delivery of triptolide against malignant melanoma.
PG  - 384
LID - 10.1186/s12951-022-01597-1 [doi]
LID - 384
AB  - BACKGROUND: Melanoma is the most malignant skin tumor and is difficult to cure 
      with the alternative treatments of chemotherapy, biotherapy, and immunotherapy. 
      Our previous study showed that triptolide (TP) exhibited powerful tumoricidal 
      activity against melanoma. However, the clinical potential of TP is plagued by 
      its poor aqueous solubility, short half-life, and biotoxicity. Therefore, 
      developing an ideal vehicle to efficiently load TP and achieving targeted 
      delivery to melanoma is a prospective approach for making full use of its 
      antitumor efficacy. RESULTS: We applied exosome (Exo) derived from human 
      umbilical cord mesenchymal stromal cells (hUCMSCs) and engineered them 
      exogenously with a cyclic peptide, arginine-glycine-aspartate (cRGD), to 
      encapsulate TP to establish a bionic-targeted drug delivery system (cRGD-Exo/TP), 
      achieving synergism and toxicity reduction. The average size of cRGD-Exo/TP was 
      157.34 +/- 6.21 nm, with a high drug loading of 10.76 +/- 1.21%. The in vitro 
      antitumor results showed that the designed Exo delivery platform could be 
      effectively taken up by targeted cells and performed significantly in 
      antiproliferation, anti-invasion, and proapoptotic activities in A375 cells via 
      the caspase cascade and mitochondrial pathways and cell cycle alteration. 
      Furthermore, the biodistribution and pharmacokinetics results demonstrated that 
      cRGD-Exo/TP possessed superior tumor targetability and prolonged the half-life of 
      TP. Notably, cRGD-Exo/TP significantly inhibited tumor growth and extended 
      survival time with negligible systemic toxicity in tumor-bearing mice. 
      CONCLUSION: The results indicated that the functionalized Exo platform provides a 
      promising strategy for targeted therapy of malignant melanoma.
CI  - (c) 2022. The Author(s).
FAU - Gu, Yongwei
AU  - Gu Y
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Fudan 
      University, Shanghai, 200032, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      200032, China.
FAU - Du, Yue
AU  - Du Y
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Fudan 
      University, Shanghai, 200032, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      200032, China.
AD  - Department of Pharmacy, Children's Hospital Affiliated to Shanghai Jiao Tong 
      University, Shanghai, 200062, China.
FAU - Jiang, Liangdi
AU  - Jiang L
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Fudan 
      University, Shanghai, 200032, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      200032, China.
AD  - School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.
FAU - Tang, Xiaomeng
AU  - Tang X
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Fudan 
      University, Shanghai, 200032, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      200032, China.
FAU - Li, Aixue
AU  - Li A
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Fudan 
      University, Shanghai, 200032, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      200032, China.
FAU - Zhao, Yunan
AU  - Zhao Y
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Fudan 
      University, Shanghai, 200032, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      200032, China.
FAU - Lang, Yitian
AU  - Lang Y
AD  - Department of Pharmacy, Huangpu Branch, Shanghai Ninth People's Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
FAU - Liu, Xiaoyan
AU  - Liu X
AD  - Department of Pharmacy, Huangpu Branch, Shanghai Ninth People's Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. 
      liuxiaoyanrj@sjtu.edu.cn.
AD  - State Key Laboratory of Quality Research in Chinese Medicine & School of 
      Pharmacy, Macau University of Science and Technology, SAR, Avenida Wai Long, 
      Taipa, 999078, Macau, China. liuxiaoyanrj@sjtu.edu.cn.
FAU - Liu, Jiyong
AU  - Liu J
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Fudan 
      University, Shanghai, 200032, China. liujiyong@fudan.edu.cn.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      200032, China. liujiyong@fudan.edu.cn.
LA  - eng
GR  - 20YF1412100/Shanghai Sailing Program/
GR  - 82074272/National Natural Science Foundation of China/
GR  - 21XD1403400/Program of Shanghai Academic Research Leader/
GR  - 20S21900300/Science and Technology Commission of Shanghai Municipality/
PT  - Journal Article
DEP - 20220823
PL  - England
TA  - J Nanobiotechnology
JT  - Journal of nanobiotechnology
JID - 101152208
RN  - 0 (Diterpenes)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Integrin alphaVbeta3)
RN  - 0 (Integrins)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (Phenanthrenes)
RN  - 19ALD1S53J (triptolide)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Diterpenes
MH  - Epoxy Compounds
MH  - *Exosomes/metabolism
MH  - Humans
MH  - Integrin alphaVbeta3/*metabolism
MH  - Integrins/metabolism
MH  - *Melanoma/drug therapy/metabolism
MH  - Mice
MH  - Peptides, Cyclic/metabolism
MH  - Phenanthrenes
MH  - *Skin Neoplasms/drug therapy
MH  - Tissue Distribution
MH  - Melanoma, Cutaneous Malignant
PMC - PMC9400227
OTO - NOTNLM
OT  - Exosomes
OT  - Malignant melanoma
OT  - Targeted delivery
OT  - Triptolide
OT  - cRGD
COIS- The authors have no conflicts of interest to declare that are relevant to the 
      content of this article.
EDAT- 2022/08/24 06:00
MHDA- 2022/08/26 06:00
PMCR- 2022/08/23
CRDT- 2022/08/23 23:40
PHST- 2022/05/26 00:00 [received]
PHST- 2022/08/16 00:00 [accepted]
PHST- 2022/08/23 23:40 [entrez]
PHST- 2022/08/24 06:00 [pubmed]
PHST- 2022/08/26 06:00 [medline]
PHST- 2022/08/23 00:00 [pmc-release]
AID - 10.1186/s12951-022-01597-1 [pii]
AID - 1597 [pii]
AID - 10.1186/s12951-022-01597-1 [doi]
PST - epublish
SO  - J Nanobiotechnology. 2022 Aug 23;20(1):384. doi: 10.1186/s12951-022-01597-1.