Lipid nanoparticle delivery of small interfering RNA targeting androgen receptor variants for prostate cancer

Quick, Joslyn

doi:10.14288/1.0378468

2019

DOI: 10.14288/1.0378468

|View full text |Cite

Lipid nanoparticle delivery of small interfering RNA targeting androgen receptor variants for prostate cancer

Joslyn Quick¹

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2020

Publication Types

Select...

Preprint1

Relationship

Self Cite0

Independent1

Authors

Journals

Cited by 1 publication

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Modular lipid nanoparticle platform technology for siRNA and lipophilic prodrug delivery

Meel

Chen

Zaifman

et al. 2020

Preprint

View full text Add to dashboard Cite

Successfully employing therapeutic nucleic acids, such as small interfering RNA (siRNA), requires chemical modifications or the use of nanocarrier technology to prevent their degradation in the circulation and to facilitate intracellular delivery. Lipid nanoparticles (LNP) are among the most advanced nanocarriers culminating in the first siRNA therapeutic's clinical translation and approval. At the same time, their applicability as modular platform technology due to the interchangeable building blocks and siRNA payload hallmarks one of LNPs' major advantages. In addition, drug derivatization approaches to synthesize lipophilic small molecule prodrugs enable stable incorporation in LNPs. This provides ample opportunities to develop combination therapies by co-encapsulating multiple therapeutic agents in a single formulation. Here, we describe how the modular LNP platform can be applied for combined gene silencing and chemotherapy to induce additive anti-cancer effects. We show that various lipophilic taxane prodrug derivatives and siRNA against the androgen receptor, a prostate cancer driver, can be efficiently and stably co-encapsulated in LNPs. In addition, we demonstrate that prodrug incorporation does not affect LNPs' gene silencing ability and that the combination therapy induces additive therapeutic effects in vitro. Using a double-radiolabeling approach, we quantitively determined the LNPs' and prodrugs' pharmacokinetic properties and biodistribution following systemic administration in tumor-bearing mice. Our results indicate that coencapsulation of siRNA and lipophilic prodrugs into LNPs is an attractive and straightforward approach for combination therapy development. GRAPHICAL ABSTRACT

show abstract

Modular lipid nanoparticle platform technology for siRNA and lipophilic prodrug delivery

Meel

Chen

Zaifman

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Lipid nanoparticle delivery of small interfering RNA targeting androgen receptor variants for prostate cancer

Cited by 1 publication

References 96 publications

Modular lipid nanoparticle platform technology for siRNA and lipophilic prodrug delivery

Modular lipid nanoparticle platform technology for siRNA and lipophilic prodrug delivery

Contact Info

Product

Resources

About