期刊
SMALL
卷 16, 期 23, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201907233
关键词
gene therapy; KRAS; layered double hydroxides; pancreatic cancer; peptide nucleic acids
类别
资金
- Shanghai Science and Technology Committee Rising-Star Program [19QA1410100]
- National Natural Science Foundation of China [21835007, 51702349]
- Science Foundation for Youth Scholar of State Key Laboratory of High Performance Ceramics and Superfine Microstructures [SKL201704]
- Youth Innovation Promotion Association of the Chinese Academy of Science (2019)
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignant tumors with extremely poor prognosis due to the later stage diagnosis when surgical resection is no longer applicable. Alternatively, the traditional gene therapy which drives pancreatic cancer cells into an inactive state and inhibiting the proliferation and metastasis, presents potentials to safely inhibit pancreatic cancer progression, but unfortunately has received limited success to date. Here, an efficient gene therapy of pancreatic cancer is shown via a peptide nucleic acid (PNA)-loaded layered double hydroxides (LDHs) nanoplatform. Compared with the traditional DNA- or RNA-based gene therapies, the gene therapy using PNA features great advantages in recognizing and hybridizing with the target mutant sequences to form PNA-DNA hybrids with significantly enhanced stability due to the absence of electrostatic repulsion, and the constrained flexibility of the polyamide backbone. Moreover, ultrasmall LDHs are engineered to load PNA and the obtained PNA-loaded LDH platform (LDHs/PNA) is capable of efficiently and selectively targeting the intranuclear mutant sequences thanks to the proton sponge effect. Treatments with LDHs/PNA demonstrate markedly inhibited growth of pancreatic cancer xenografts via a cancer cell proliferation suppression mechanism. The results demonstrate the great potentials of LDHs/PNA as a highly promising gene therapy agent for PDAC.
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