Efficient Gene Therapy of Pancreatic Cancer via a Peptide Nucleic Acid (PNA)‐Loaded Layered Double Hydroxides (LDH) Nanoplatform

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 16; no. 23; pp. e1907233 - n/a
• Main Authors: Yu, Zhiguo, Hu, Ping, Xu, Yingying, Bao, Qunqun, Ni, Dalong, Wei, Chenyang, Shi, Jianlin
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-06-2020
• Subjects: Cancer; Deoxyribonucleic acid; DNA; Feature recognition; Gene sequencing; Gene therapy; Hydroxides; KRAS; layered double hydroxides; Nanotechnology; Pancreatic cancer; peptide nucleic acids; Peptides; Polyamide resins; Xenotransplantation; gene therapy; layered double hydroxides; pancreatic cancer; KRAS; peptide nucleic acids
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201907233

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deadliest malignant tumors with extremely poor prognosis due to the later stage diagnosis when surgical resection is no longer applicable.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.
A peptide nucleic acid (PNA)‐based gene therapy shows promise for safely inhibiting pancreatic cancer progression and metastasis via V‐Ki‐ras2 Kirsten ratsarcoma viral oncogene homolog mutation silencing. Treatments with layered double hydroxide loaded PNA demonstrate markedly inhibited growth of pancreatic cancer xenografts, and consequently, the 100% survival rate of pancreatic ductal adenocarcinoma xenografted mice for at least 60 days.