Poly(lactide-co-glycolide) Nanoparticles Mediate Sustained Gene Silencing and Improved Biocompatibility of siRNA Delivery Systems in Mouse Lungs after Pulmonary Administration

2021 ◽  
Vol 13 (3) ◽  
pp. 3722-3737
Author(s):  
Lan Wu ◽  
Lin-Ping Wu ◽  
Jingya Wu ◽  
Jin Sun ◽  
Zhonggui He ◽  
...  
2020 ◽  
Vol 6 (30) ◽  
pp. eaba5379 ◽  
Author(s):  
Md. Nazir Hossen ◽  
Lin Wang ◽  
Harisha R. Chinthalapally ◽  
Joe D. Robertson ◽  
Kar-Ming Fung ◽  
...  

Gene silencing using small-interfering RNA (siRNA) is a viable therapeutic approach; however, the lack of effective delivery systems limits its clinical translation. Herein, we doped conventional siRNA-liposomal formulations with gold nanoparticles to create “auroliposomes,” which significantly enhanced gene silencing. We targeted MICU1, a novel glycolytic switch in ovarian cancer, and delivered MICU1-siRNA using three delivery systems—commercial transfection agents, conventional liposomes, and auroliposomes. Low-dose siRNA via transfection or conventional liposomes was ineffective for MICU1 silencing; however, in auroliposomes, the same dose gave >85% gene silencing. Efficacy was evident from both in vitro growth assays of ovarian cancer cells and in vivo tumor growth in human ovarian cell line—and patient-derived xenograft models. Incorporation of gold nanoparticles shifted intracellular uptake pathways such that liposomes avoided degradation within lysosomes. Auroliposomes were nontoxic to vital organs. Therefore, auroliposomes represent a novel siRNA delivery system with superior efficacy for multiple therapeutic applications.


Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2692 ◽  
Author(s):  
Francesco Mainini ◽  
Michael R. Eccles

RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient’s therapeutic response.


2012 ◽  
Vol 39 (5) ◽  
pp. 396-401 ◽  
Author(s):  
Wen-Juan DONG ◽  
Yin-Jian ZHOU ◽  
Wei LIANG

2021 ◽  
Vol 331 ◽  
pp. 246-259
Author(s):  
David Vetvicka ◽  
Ladislav Sivak ◽  
Chinmay M. Jogdeo ◽  
Raj Kumar ◽  
Rubayat Khan ◽  
...  

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 682
Author(s):  
Andreea Crintea ◽  
Alina Gabriela Dutu ◽  
Gabriel Samasca ◽  
Ioan Alexandru Florian ◽  
Iulia Lupan ◽  
...  

Even though there are various types of cancer, this pathology as a whole is considered the principal cause of death worldwide. Lung cancer is known as a heterogeneous condition, and it is apparent that genome modification presents a significant role in the occurrence of this disorder. There are conventional procedures that can be utilized against diverse cancer types, such as chemotherapy or radiotherapy, but they are hampered by the numerous side effects. Owing to the many adverse events observed in these therapies, it is imperative to continuously develop new and improved strategies for managing individuals with cancer. Nanomedicine plays an important role in establishing new methods for detecting chromosomal rearrangements and mutations for targeted chemotherapeutics or the local delivery of drugs via different types of nano-particle carriers to the lungs or other organs or areas of interest. Because of the complex signaling pathways involved in developing different types of cancer, the need to discover new methods for prevention and detection is crucial in producing gene delivery materials that exhibit the desired roles. Scientists have confirmed that nanotechnology-based procedures are more effective than conventional chemotherapy or radiotherapy, with minor side effects. Several nanoparticles, nanomaterials, and nanosystems have been studied, including liposomes, dendrimers, polymers, micelles, inorganic nanoparticles, such as gold nanoparticles or carbon nanotubes, and even siRNA delivery systems. The cytotoxicity of such nanosystems is a debatable concern, and nanotechnology-based delivery systems must be improved to increase the bioavailability, biocompatibility, and safety profiles, since these nanosystems boast a remarkable potential in many biomedical applications, including anti-tumor activity or gene therapy. In this review, the nanosystems involved in treating lung cancer and its associated challenges are discussed.


Polymer ◽  
2021 ◽  
pp. 123680
Author(s):  
Sung Hyun Cho ◽  
Ho-Joong Kim ◽  
Dong-Hyun Lee ◽  
Si Kyung Yang

2014 ◽  
Vol 24 (5) ◽  
pp. 445-451 ◽  
Author(s):  
HongYan Zhu ◽  
JingPing Zhu ◽  
AiMei Xie ◽  
Yong Lin ◽  
BeiBei Zhang ◽  
...  

2014 ◽  
Vol 196 ◽  
pp. 355-362 ◽  
Author(s):  
Vikas Hegde ◽  
Robyn P. Hickerson ◽  
Sitheswaran Nainamalai ◽  
Paul A. Campbell ◽  
Frances J.D. Smith ◽  
...  

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