期刊
BIOENGINEERING & TRANSLATIONAL MEDICINE
卷 8, 期 5, 页码 -出版社
WILEY
DOI: 10.1002/btm2.10558
关键词
CN-based nanosheets; gene delivery; gene therapy; light controlled; non-cationic carrier
The study proposes the concept of self-escape non-cationic gene carriers for targeted delivery and treatment of hepatocellular carcinoma (HCC) using graphitic carbon nitride nanosheets. These nanocomplexes actively target HCC tissue and disrupt lysosome structure to facilitate their escape. They also promote reversible release of DNA in the acidic microenvironment of HCC tissue and effectively upregulate tumor suppressor protein P53 expression for gene therapy of HCC.
High positive charge-induced toxicity, easy lysosomal degradation of nucleic acid drugs, and poor lesion sites targeting are major problems faced in the development of gene carriers. Herein, we proposed the concept of self-escape non-cationic gene carriers for targeted delivery and treatment of photocontrolled hepatocellular carcinoma (HCC) with sufficient lysosome escape and multiple response capacities. Functional DNA was bound to the surface of biotin-PEG(2000)-modified graphitic carbon nitride (Bio-PEG-CN) nanosheets to form non-cationic nanocomplexes Bio-PEG-CN/DNA. These nanocomposites could actively target HCC tissue. Once these nanocomplexes were taken up by tumor cells, the accumulated reactive oxygen species (ROS) generated by Bio-PEG-CN under LED irradiation would disrupt the lysosome structure, thereby facilitating nanocomposites escape. Due to the acidic microenvironment and lipase in the HCC tissue, the reversible release of DNA could be promoted to complete the transfection process. Meanwhile, the fluorescence signal of Bio-PEG-CN could be monitored in real time by fluorescence imaging technology to investigate the transfection process and mechanism. In vitro and in vivo results further demonstrated that these nanocomplexes could remarkably upregulate the expression of tumor suppressor protein P53, increased tumor sensitivity to ROS generated by nanocarriers, and realized effective gene therapy for HCC via loading P53 gene.
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