Anti-seed PNAs targeting multiple oncomiRs for brain tumor therapy

被引：24

作者：

Wang, Yazhe ^{[1
]}

Malik, Shipra ^{[2
]}

Suh, Hee-Won ^{[1
]}

Xiao, Yong ^{[1
]}

Deng, Yanxiang ^{[1
]}

Fan, Rong ^{[1
]}

Huttner, Anita ^{[3
]}

Bindra, Ranjit S. ^{[4
]}

Singh, Vijender ^{[5
]}

Saltzman, W. Mark ^{[1
]}

Bahal, Raman ^{[2
]}

机构：

[1] Yale Univ, Dept Biomed Engn, New Haven, CT 06511 USA

[2] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA

[3] Yale Univ, Dept Pathol, New Haven, CT 06510 USA

[4] Yale Univ, Dept Therapeut Radiol, New Haven, CT 06510 USA

[5] Univ Connecticut, Inst Syst Genom, Computat Biol Core, Storrs, CT 06269 USA

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 06期

关键词：

CONVECTION-ENHANCED DELIVERY; PEPTIDE NUCLEIC-ACIDS; IN-VIVO; DRUG-DELIVERY; GLIOMA GROWTH; GLIOBLASTOMA; MICRORNA-21; GENE; NANOPARTICLES; TEMOZOLOMIDE;

D O I：

10.1126/sciadv.abq7459

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Glioblastoma (GBM) is one of the most lethal malignancies with poor survival and high recurrence rates. Here, we aimed to simultaneously target oncomiRs 10b and 21, reported to drive GBM progression and invasiveness. We designed short (8-mer) gamma-modified peptide nucleic acids (s gamma PNAs), targeting the seed region of oncomiRs 10b and 21. We entrapped these anti-miR s gamma PNAs in nanoparticles (NPs) formed from a block copolymer of pol-y(lactic acid) and hyperbranched polyglycerol (PLA-HPG). The surface of the NPs was functionalized with alde-hydes to produce bioadhesive NPs (BNPs) with superior transfection efficiency and tropism for tumor cells. When combined with temozolomide, s gamma PNA BNPs administered via convection-enhanced delivery (CED) mark-edly increased the survival (>120 days) of two orthotopic (intracranial) mouse models of GBM. Hence, we estab-lished that BNPs loaded with anti-seed s gamma PNAs targeting multiple oncomiRs are a promising approach to improve the treatment of GBM, with a potential to personalize treatment based on tumor-specific oncomiRs.

引用

页数：19

共 79 条

[1] Adult Glioblastoma [J].