An NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles for tumor targeted drug delivery in vitro and in vivo.
The synthesis and characterization of an
quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles (MSNPs) for on-command delivery applications has been described in this paper. Gatekeeping of MSNPs is achieved by the integration of mechanically interlocked rotaxane nanovalves on the surface of MSNPs. The rotaxane nanovalve system is composed of a linear stalk anchoring on the surface of MSNPs, an α-cyclodextrin ring that encircles it and locks the payload "cargo" molecules in the mesopores, and a benzoquinone stopper incorporated at the end of the stalk. The gate opening and controlled release of the cargo are triggered by cleavage of the benzoquinone stopper using an endogenous NQO1 enzyme. In addition to having efficient drug loading and controlled release mechanisms, this smart biocompatible carrier system showed obvious uptake and consequent release of the drug in tumor cells, could selectively induce the tumor cell death and enhance the capability of inhibition of tumor growth in vivo. The controlled drug delivery system demonstrated its use as a potential theranostic material.
National Chiao Tung University, Department of Applied Chemistry, Science Building 2, 1001 Ta Hsueh Road, Hsinchu, 300 Taiwan. spwu@mail.nctu.edu.tw.
Srivardhan Reddy
SR
Gayam
National Chiao Tung University, Department of Applied Chemistry, Science Building 2, 1001 Ta Hsueh Road, Hsinchu, 300 Taiwan. spwu@mail.nctu.edu.tw.
Parthiban
P
Venkatesan
National Chiao Tung University, Department of Applied Chemistry, Science Building 2, 1001 Ta Hsueh Road, Hsinchu, 300 Taiwan. spwu@mail.nctu.edu.tw.
Yi-Ming
YM
Sung
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
Shuo-Yuan
SY
Sung
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
Shang-Hsiu
SH
Hu
National Chiao Tung University, Department of Applied Chemistry, Science Building 2, 1001 Ta Hsueh Road, Hsinchu, 300 Taiwan. spwu@mail.nctu.edu.tw.
Hsin-Yun
HY
Hsu
National Chiao Tung University, Department of Applied Chemistry, Science Building 2, 1001 Ta Hsueh Road, Hsinchu, 300 Taiwan. spwu@mail.nctu.edu.tw.
Shu-Pao
SP
Wu
D000072283:A549 Cells; D000818:Animals; D016503:Drug Delivery Systems; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D016062:Porosity; D012822:Silicon Dioxide; D023041:Xenograft Model Antitumor Assays
D012822:Silicon Dioxide; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human