Tailored protein-conjugated DNA nanoplatform for synergistic cancer therapy

被引:16
作者
Liu, Dingkang [1 ]
Chen, Ye [1 ]
Wang, Qun [1 ]
Ji, Yue [1 ]
Bao, Lichen [1 ]
Yao, Wenbing [1 ]
Gao, Xiangdong [1 ]
Yin, Jun [1 ]
机构
[1] China Pharmaceut Univ, Sch Life Sci & Technol, Jiangsu Key Lab Druggabil Biopharmaceut, State Key Lab Nat Med, Nanjing 210009, Peoples R China
基金
中国国家自然科学基金;
关键词
Cancer; Multidrug resistance; Drug delivery; DNA nanotechnology; Peptide therapeutics; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; DELIVERY; PEPTIDE; NANOTECHNOLOGY; NANOCARRIERS; TRANSPORTERS; PRODRUG; FUSION; ATP;
D O I
10.1016/j.jconrel.2022.04.022
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Multidrug resistance (MDR) to chemotherapeutic drugs and targeted drug delivery are recurring issues in clinical cancer treatment. Here, a multifunctional fusion protein-DNA conjugate was designed as a co-delivery vehicle for anticancer peptides and chemotherapeutic drugs to combat both drug-resistant and drug-sensitive tumor cells. The fusion protein was constructed by fusing a PsTag polypeptide, a matrix metalloproteinase 2 (MMP2)degradable domain, and the mitochondria-targeted pro-apoptotic peptide KLAKLAKKLAKLAK. Doxorubicin was efficiently loaded into the fusion protein pre-conjugated dendrimer-like DNA nanostructure. With the incorporation of enhanced stability, tumor targeting, and controlled-release elements, the tailored nanostructure can selectively enter tumor cells and synergistically exert antitumor activity with no significant adverse effects. Thus, these protein-conjugated DNA nanocarriers could be a potential co-delivery system for protein/peptide and chemotherapeutic drugs delivery in synergistic cancer therapy.
引用
收藏
页码:250 / 259
页数:10
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