Photoactivation of sulfonated polyplexes enables localized gene silencing by DsiRNA in breast cancer cells.
Photoactivation of sulfonated polyplexes enables localized gene silencing by DsiRNA in breast cancer cells.
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DOI：
10.1016/j.nano.2020.102176
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发表时间：
2020-06
期刊：
影响因子：
--
通讯作者：
Shapiro BA
中科院分区：
文献类型：
--
作者：
Puri A;Viard M;Zakrevsky P;Zampino S;Chen A;Isemann C;Alvi S;Clogston J;Chitgupi U;Lovell JF;Shapiro BA
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. A novel photoactivatable “trap and release” polymer-based RNAi nanotherapeutics is developed for regulated intracellular siRNA release within defined time and space for site specific gene knockdown. A polyethylenimine polymer (PEI) is covalently linked to a photosensitizer “pyro” that can be activated in far red region for future in vivo applications. Pyro-PEI is further sulfonated (sulfo-pyro-PEI) to modulate protonation at low pH of the endosome. Sulfo-pyro-PEI/DsiRNA polyplexes only promote gene silencing upon photoactivation by a 661 nm laser light source. This nanosystem offers the potential for site-specific RNAi while minimizing off-target effects.
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DOI：
10.1016/j.jconrel.2018.06.001
发表时间：
2018-08-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Jiang Y;Hardie J;Liu Y;Ray M;Luo X;Das R;Landis RF;Farkas ME;Rotello VM
通讯作者：
Rotello VM
DOI：
10.2217/nnm.15.105
发表时间：
2015
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Gupta K;Mattingly SJ;Knipp RJ;Afonin KA;Viard M;Bergman JT;Stepler M;Nantz MH;Puri A;Shapiro BA
通讯作者：
Shapiro BA
影响因子：
3.3
作者：
Chitgupi U;Li Y;Chen M;Shao S;Beitelshees M;Tan MJ;Neelamegham S;Pfeifer BA;Jones C;Lovell JF
通讯作者：
Lovell JF
DOI：
10.1007/978-1-60761-697-9_10
发表时间：
2010-01-01
期刊：
PHOTODYNAMIC THERAPY: METHODS AND PROTOCOLS
影响因子：
--
作者：
Berg, Kristian;Weyergang, Anette;Selbo, Pal K.
通讯作者：
Selbo, Pal K.
影响因子：
46.9
作者：
Kim, DH;Behlke, MA;Rossi, JJ
通讯作者：
Rossi, JJ