Enhanced siRNA Delivery Using a Combination of an Arginine-Grafted Bioreducible Polymer, Ultrasound, and Microbubbles in Cancer Cells

Florinas, Stelios; Nam, Hye Yeong; Kim, Sung Wan

doi:10.1021/mp400048p

Cited by 24 publications

(20 citation statements)

References 27 publications

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“…As described previously, SAM complexes can be formed in serum free media by combining positive charged polyplexes (ABP-siRNA) with negatively charged MBs due to electrostatic interaction [24]. Thus, it is a reasonable concern for SAM complex formation to be disrupted in serum-containing media.…”

Section: Resultsmentioning

confidence: 99%

“…Arginine-grafted bioreducible poly(disulfide amine) (ABP)–siRNA polyplexes, polyethyleneimine (PEI)–siRNA polyplexes, siRNA plus microbubbles (MB), naked siRNA and siRNA-ABP-Microbubble (SAM) complexes were prepared as described previously [20,24]. Briefly, polyplexes (ABP-siRNA, PEI-siRNA) were prepared by adding a HEPES buffer solution containing ABP to a HEPES buffer solution of siRNA at a weight ratio 10:1 (w/w; ABP to siRNA), or 1:1 (w/w; PEI to siRNA), followed by gentle shaking.…”

Section: Methodsmentioning

confidence: 99%

“…ABP, HSA were labeled with FITC and siRNA with Cy3 dye at the 3′-terminal end of the sense strand as described previously [24]. SAM complexes were produced as described above.…”

Section: Methodsmentioning

confidence: 99%

“…Our hypothesis is that current obstacles in siRNA delivery can be overcome by synergizing advantages of each delivery system by combining them into one application. We previously described the formation of SAM complexes by electrostatic interaction of negatively charged albumin MB and positively charged polyplexes (ABP-siRNA) [24]. SAM complexes have a size range of 1–5 μM and a flexible zeta-potential that can be tuned from positive to negative depending on the concentration of polyplexes loaded on the outer MB shell.…”

Section: Introductionmentioning

confidence: 99%

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Ultrasound-assisted siRNA delivery via arginine-grafted bioreducible polymer and microbubbles targeting VEGF for ovarian cancer treatment

Florinas

Kim

Nam

et al. 2014

Journal of Controlled Release

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The major drawback hampering siRNA therapies from being more widely accepted in clinical practice is its insufficient accumulation at the target site mainly due to poor cellular uptake and rapid degradation in serum. Therefore, we designed a novel polymeric siRNA carrier system, which would withstand serum-containing environments and tested its performance in vitro as well as in vivo. Delivering siRNA with a system combining an arginine-grafted bioreducible polymer (ABP), microbubbles (MB), and ultrasound technology (US) we were able to synergize the advantages each delivery system owns individually, and created our innovative siRNA-ABP-MB (SAM) complexes. SAM complexes show significantly higher siRNA uptake and VEGF protein knockdown in vitro with serum-containing media when compared to naked siRNA, and 25k-branched-polyethylenimine (bPEI) representing the current standard in nonviral gene therapy. SAM complexes activated by US are also able to improve siRNA uptake in tumor tissue resulting in decelerating tumor growth in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…ABP, HSA were labeled with FITC and siRNA with Cy3 dye at the 3′-terminal end of the sense strand as described previously [24]. SAM complexes were produced as described above.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ultrasound-assisted siRNA delivery via arginine-grafted bioreducible polymer and microbubbles targeting VEGF for ovarian cancer treatment

Florinas

Kim

Nam

et al. 2014

Journal of Controlled Release

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“…However, DNA delivery with MB shows only moderate DNA uptake and expression due to degradation of the released DNA at the target site by extracellular nucleases and due to poor cellular uptake efficiency. Therefore, a combination of MBs with nonviral polycationic polymeric carriers can overcome the disadvantages of MBs used as a gene delivery system alone [119]. The siRNA-ABP-MB (SAM) complexes in combination with US showed significant VEGF knock down in A2780 human ovarian cancer cell line compared to naked siRNA when incubated for a short time after sonication treatment [119].…”

Section: Disease Applications Of Bioreducible Polymersmentioning

confidence: 99%

Bioreducible polymers for therapeutic gene delivery

Lee

Kim

2014

Journal of Controlled Release

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Most currently available cationic polymers have significant acute toxicity concerns such as cellular toxicity, aggregation of erythrocytes, and entrapment in the lung capillary bed, largely due to their poor biocompatibility and non-degradability under physiological conditions. To develop more intelligent polymers, disulfide bonds are introduced in the design of biodegradable polymers. Herein, the sustained innovations of biomimetic nanosized constructs with bioreducible poly(disulfide amine)s demonstrate a viable clinical tool for the treatment of cardiovascular disease, anemia, diabetes, and cancer.

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Development and Perspectives: Multifunctional Nucleic Acid Nanomedicines for Treatment of Gynecological Cancers

Korzun

Moses

Diba

et al. 2023

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Gynecological malignancies are a significant cause of morbidity and mortality across the globe. Due to delayed presentation, gynecological cancer patients are often referred late in the disease's course, resulting in poor outcomes. A considerable number of patients ultimately succumb to chemotherapy‐resistant disease, which reoccurs at advanced stages despite treatment interventions. Although efforts have been devoted to developing therapies that demonstrate reduced resistance to chemotherapy and enhanced toxicity profiles, current clinical outcomes remain unsatisfactory due to treatment resistance and unfavorable off‐target effects. Consequently, innovative biological and nanotherapeutic approaches are imperative to strengthen and optimize the therapeutic arsenal for gynecological cancers. Advancements in nanotechnology‐based therapies for gynecological malignancies offer significant advantages, including reduced toxicity, expanded drug circulation, and optimized therapeutic dosing, ultimately leading to enhanced treatment effectiveness. Recent advances in nucleic acid therapeutics using microRNA, small interfering RNA, and messenger RNA provide novel approaches for cancer therapeutics. Effective single‐agent and combinatorial nucleic acid therapeutics for gynecological malignancies have the potential to transform cancer treatment by giving safer, more tailored approaches than conventional therapies. This review highlights current preclinical studies that effectively exploit these approaches for the treatment of gynecological malignant tumors and malignant ascites.

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Enhanced siRNA Delivery Using a Combination of an Arginine-Grafted Bioreducible Polymer, Ultrasound, and Microbubbles in Cancer Cells

Cited by 24 publications

References 27 publications

Ultrasound-assisted siRNA delivery via arginine-grafted bioreducible polymer and microbubbles targeting VEGF for ovarian cancer treatment

Ultrasound-assisted siRNA delivery via arginine-grafted bioreducible polymer and microbubbles targeting VEGF for ovarian cancer treatment

Bioreducible polymers for therapeutic gene delivery

Development and Perspectives: Multifunctional Nucleic Acid Nanomedicines for Treatment of Gynecological Cancers

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