DNA-Hybrid-Gated Photothermal Mesoporous Silica Nanoparticles for NIR-Responsive and Aptamer-Targeted Drug Delivery.
Near-infrared light is an attractive stimulus due to its noninvasive and deep tissue penetration. Particularly, NIR light is utilized for cancer thermotherapy and on-demand release of drugs by the disruption of the delivery carriers. Here we have prepared a novel NIR-responsive DNA-hybrid-gated nanocarrier based on mesoporous silica-coated Cu1.8S nanoparticles. Cu1.8S nanoparticles, possessing high photothermal conversion efficiency under a 980 nm laser, were chosen as photothermal agents. The mesoporous silica structure could be used for drug storage/delivery and modified with aptamer-modified GC-rich DNA-helix as gatekeepers, drug vectors, and targeting ligand. Simultaneously, the as-produced photothermal effect caused denaturation of DNA double strands, which triggered the drug release of the DNA-helix-loaded hydrophilic drug doxorubicin and mesopore-loaded hydrophobic drug curcumin, resulting in a synergistic therapeutic effect. The Cu1.8S@mSiO2 nanocomposites endocytosed by cancer cells through the aptamer-mediated mode are able to generate rational release of doxorubicin/curcumin under NIR irradiation, strongly enhancing the synergistic growth-inhibitory effect of curcumin against doxorubicin in MCF-7 cells, which is associated with a strong mitochondrial-mediated cell apoptosis progression. The underlying mechanism of apoptosis showed a strong synergistic inhibitory effect both on the expression of Bcl-2, Bcl-xL, Mcl-1, and upregulated caspase 3/9 activity and on the expression level of Bak and Bax. Therefore, Cu1.8S@mSiO2 with efficient synergistic therapeutic efficiency is a potential multifunctional cancer therapy nanoplatform.
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.|College of Biology and Food Engineering, Jilin Institute of Chemical Technology , Jilin 132022, P. R. China.
Yuanxin
Y
Zhang
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
Zhiyao
Z
Hou
College of Biology and Food Engineering, Jilin Institute of Chemical Technology , Jilin 132022, P. R. China.
Yakun
Y
Ge
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.|University of Chinese Academy of Sciences , Beijing 100049, P. R. China.
Kerong
K
Deng
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.|University of Chinese Academy of Sciences , Beijing 100049, P. R. China.
Bei
B
Liu
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.|University of Chinese Academy of Sciences , Beijing 100049, P. R. China.
Xuejiao
X
Li
School of Life Science, Jilin University , Changchun 130012, P. R. China.
Quanshun
Q
Li
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
Ziyong
Z
Cheng
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
Ping'an
P
Ma
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
Chunxia
C
Li
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
Jun
J
Lin
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry; D003474:Curcumin / Q000494:pharmacology; D004247:DNA; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008027:Light; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D054118:Nanospheres / Q000737:chemistry; D016062:Porosity; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013696:Temperature
D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; D003300:Copper; D004317:Doxorubicin; D004247:DNA; D003474:Curcumin
NIR light; aptamer; copper sulfide; mesoporous silica; photothermal conversion; synergistic effect