Targeting the undruggable in pancreatic cancer using nano-based gene silencing drugs

被引：52

作者：

Kokkinos, John ^{[1
,2
]}

Ignacio, Rosa Mistica C. ^{[1
]}

Sharbeen, George ^{[1
]}

Boyer, Cyrille ^{[2
,3
]}

Gonzales-Aloy, Estrella ^{[1
]}

Goldstein, David ^{[1
,4
]}

McCarroll, Joshua A. ^{[2
,5
,6
]}

Phillips, Phoebe A. ^{[1
,2
]}

机构：

[1] UNSW, Sch Med Sci, Lowy Canc Res Ctr, Pancreat Canc Translat Res Grp, Sydney, NSW 2052, Australia

[2] UNSW, Australian Ctr Nanomed, Sydney, NSW 2052, Australia

[3] UNSW, Sch Chem Engn, Ctr Adv Macromol Design, Sydney, NSW 2052, Australia

[4] Prince Wales Hosp, Prince Wales Clin Sch, Sydney, NSW 2052, Australia

[5] UNSW, Childrens Canc Inst, Lowy Canc Res Ctr, Tumour Biol & Targeting Program, Sydney, NSW 2031, Australia

[6] UNSW, Sch Womens & Childrens Hlth, Fac Med, Sydney, NSW 2052, Australia

来源：

BIOMATERIALS | 2020年 / 240卷

基金：

英国医学研究理事会;

关键词：

Pancreatic cancer; Nanomedicine; Nanoparticles; RNA-Interference; Small interfering RNA; SYSTEMICALLY ADMINISTERED SIRNA; SMALL INTERFERING RNA; STELLATE CELLS; CO-DELIVERY; IN-VITRO; TUMOR-GROWTH; NANOPARTICLES; THERAPY; STROMA; NANOMEDICINE;

D O I：

10.1016/j.biomaterials.2019.119742

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Pancreatic cancer is predicted to be the second leading cause of cancer-related death by 2025. The best chemotherapy only extends survival by an average of 18 weeks. The extensive fibrotic stroma surrounding the tumor curbs therapeutic options as chemotherapy drugs cannot freely penetrate the tumor. RNA interference (RNAi) has emerged as a promising approach to revolutionize cancer treatment. Small interfering RNA (siRNA) can be designed to inhibit the expression of any gene which is important given the high degree of genetic heterogeneity present in pancreatic tumors. Despite the potential of siRNA therapies, there are hurdles limiting their clinical application such as poor transport across biological barriers, limited cellular uptake, degradation, and rapid clearance. Nanotechnology can address these challenges. In fact, the past few decades have seen the conceptualization, design, pre-clinical testing and recent clinical approval of a RNAi nanodrug to treat disease. In this review, we comment on the current state of play of clinical trials evaluating siRNA nanodrugs and review pre-clinical studies investigating the efficacy of siRNA therapeutics in pancreatic cancer. We assess the physiological barriers unique to pancreatic cancer that need to be considered when designing and testing new nanomedicines for this disease.

引用

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