Photoactivation of sulfonated polyplexes enables localized gene silencing by DsiRNA in breast cancer cells.

Nanomedicine : Nanotechnology, Biology, and Medicine
Anu PuriBruce A Shapiro

Abstract

Translation potential of RNA interference nanotherapeutics remains challenging due to in vivo off-target effects and poor endosomal escape. Here, we developed novel polyplexes for controlled intracellular delivery of dicer substrate siRNA, using a light activation approach. Sulfonated polyethylenimines covalently linked to pyropheophorbide-α for photoactivation and bearing modified amines (sulfo-pyro-PEI) for regulated endosomal escape were investigated. Gene knock-down by the polymer-complexed DsiRNA duplexes (siRNA-NPs) was monitored in breast cancer cells. Surprisingly, sulfo-pyro-PEI/siRNA-NPs failed to downregulate the PLK1 or eGFP proteins. However, photoactivation of these cell associated-polyplexes with a 661-nm laser clearly restored knock-down of both proteins. In contrast, protein down-regulation by non-sulfonated pyro-PEI/siRNA-NPs occurred without any laser treatments, indicating cytoplasmic disposition of DsiRNA followed a common intracellular release mechanism. Therefore, sulfonated pyro-PEI holds potential as a unique trap and release light-controlled delivery platform for on-demand gene silencing bearing minimal off target effects.

References

Aug 2, 1994·Proceedings of the National Academy of Sciences of the United States of America·A Varki
Oct 6, 1998·Annual Review of Biochemistry·R G Anderson
Dec 28, 2004·Nature Biotechnology·Dong-Ho KimJohn J Rossi
Jul 29, 2005·Nucleic Acids Research·Scott D RoseMark A Behlke
Dec 13, 2005·Gene Therapy·S I PaiT-C Wu
Dec 22, 2006·Nature Reviews. Molecular Cell Biology·Tariq M Rana
Feb 12, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Srinivas GantaMansoor Amiji
Apr 21, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Tamaki EndohTakashi Ohtsuki
Jan 12, 2010·Journal of Internal Medicine·B OzpolatG Lopez-Berestein
Jun 17, 2010·Methods in Molecular Biology·Kristian BergPål K Selbo
Jul 9, 2010·American Journal of Ophthalmology·Peter K KaiserUNKNOWN Sirna-027 Study Investigators
Nov 26, 2010·Nature Nanotechnology·Peixuan Guo
Mar 1, 2012·Accounts of Chemical Research·Yuka Matsushita-Ishiodori, Takashi Ohtsuki
Jun 28, 2012·BMC Biology·Kuan-Teh Jeang
Aug 8, 2012·Integrative Biology : Quantitative Biosciences From Nano to Macro·Lin Zhu, Vladimir P Torchilin
Jan 2, 2013·Frontiers in Bioscience (Landmark Edition)·Tiziana Musacchio, Vladimir P Torchilin
Jan 19, 2013·Chinese Journal of Cancer·Wei GuoWuguo Deng
Jun 19, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Afrouz YousefiEnrico Mastrobattista
Aug 14, 2013·British Journal of Pharmacology·A Guzman-AranguezJ Pintor
Oct 24, 2013·Nature Materials·Rosemary KanastyDaniel Anderson
Nov 26, 2013·Advanced Drug Delivery Reviews·Yi ShuPeixuan Guo
Nov 28, 2013·Pharmaceuticals·Olivia KoenigAndrea Nolte
Feb 12, 2014·Proceedings of the National Academy of Sciences of the United States of America·Julia VoigtV Prasad Shastri
Apr 16, 2014·Journal of Nanoscience and Nanotechnology·Harshad K SheteVandana B Patravale
Apr 25, 2014·Accounts of Chemical Research·Kirill A AfoninBruce A Shapiro
Aug 3, 2014·American Journal of Physiology. Lung Cellular and Molecular Physiology·Agnieszka KrupaAnna K Kurdowska
Sep 27, 2014·Molecular Cancer Research : MCR·Thomas M BodenstineMary J C Hendrix
Nov 21, 2014·Advances in Genetics·Ernst Wagner
Nov 21, 2014·Advances in Genetics·Patrick Neuberg, Antoine Kichler
Feb 11, 2015·Advanced Drug Delivery Reviews·Gulnihal OzcanGabriel Lopez-Berestein
Jun 10, 2015·Bioconjugate Chemistry·Upendra ChitgupiJonathan F Lovell
Jul 21, 2015·Nature Biotechnology·Anders WittrupJudy Lieberman
Oct 22, 2015·Current Pharmaceutical Design·Giuseppina SalzanoVladimir P Torchilin
Jan 8, 2016·Annual Review of Pharmacology and Toxicology·Maggie L Bobbin, John J Rossi
Feb 11, 2016·Wiener medizinische Wochenschrift·Sarah R ElkinSandra L Schmid
Apr 26, 2016·British Journal of Clinical Pharmacology·Kannan Sridharan, Nithya Jaideep Gogtay
Aug 11, 2016·ACS Combinatorial Science·Lorena ParleaBruce A Shapiro
Dec 10, 2016·Photochemistry and Photobiology·Upendra ChitgupiJonathan F Lovell

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.