Cytocompatibility, membrane disruption, and siRNA delivery using environmentally responsive cationic nanogels

Spencer, David S.; Shodeinde, Aaliyah B.; Beckman, David W.; Luu, Bryan C.; Hodges, Hannah R.; Peppas, Nicholas A.

doi:10.1016/j.jconrel.2021.03.004

Cited by 14 publications

(22 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Peppas research group has recently developed a nanoscale pH‐responsive cationic hydrogel and evaluated the synthesized materials for cytocompatibility, membrane disruption (hemolysis), therapeutic loading and transfection of siRNA and their physicochemical dependent biological effects. [ 168 ] The most influential nanogel property identified to directly correlate to toxicity, hemolytic activity is nanogel pKa. From in vitro studies, it was determined that nanogels with pKa values in the range of 6.5–7.05 are the most promising formulations, producing over 60% cell viability and over 40% GFP expression (used to assess transfection).…”

Section: Treating Diseases Resulting From Chronic Exposure To Environ...mentioning

confidence: 99%

“…Finally, the most successful hydrogels for delivery of siRNA, or other therapeutics, exhibited the lowest degrees of cytotoxicity and pH‐dependent cell membrane disruption potential, highest siRNA loading, and highest transfection efficacies ( Figure ). [ 168 ] This nanogel platform shows great promise as a drug delivery platform for a variety of chronic diseases.…”

Section: Treating Diseases Resulting From Chronic Exposure To Environ...mentioning

confidence: 99%

“…), and/or 4) less invasiveness thanks to ease of injectability. [ 161–169 ] Our group has extensively studied magnetic hydrogel nanocomposite for cancer therapy applications such as controlled drug delivery, controlled thermal delivery, and combinations of these therapies [ 170–176 ] There have also been a few insightful reviews highlighting the breadth of activities in this area. [ 177–179 ]…”

Section: Treating Diseases Resulting From Chronic Exposure To Environ...mentioning

confidence: 99%

“…), and/or 4) less invasiveness thanks to ease of injectability. [161][162][163][164][165][166][167][168][169] Our group has extensively studied magnetic hydrogel nanocomposite for cancer therapy applications such as controlled drug delivery, controlled thermal delivery, and combinations of these therapies [170][171][172][173][174][175][176] There have also been a few insightful reviews highlighting the breadth of activities in this area. [177][178][179] Injectable hydrogels have gained interest for tumor treatment because of their ability to be locally administered, high swelling capacity, which can increase contact area between the therapeutic gel and irregularly shaped/distributed carcinoma, in situ polymerization capability as a response to external stimulus (i.e., like pH or temperature), ability to mimic the biological environment, prevent degradation of the drug during transport, and enhanced localized therapeutic effects.…”

Section: Treating Cancer With Hydrogels and Hydrogel Nanocompositesmentioning

confidence: 99%

mentioning

confidence: 99%

See 4 more Smart Citations

Hydrogels and Hydrogel Nanocomposites: Enhancing Healthcare through Human and Environmental Treatment

Gutiérrez

Frazar

Klaus

et al. 2021

Adv Healthcare Materials

View full text Add to dashboard Cite

Humans are constantly exposed to exogenous chemicals throughout their life, which can lead to a multitude of negative health impacts. Advanced materials can play a key role in preventing or mitigating these impacts through a wide variety of applications. The tunable properties of hydrogels and hydrogel nanocomposites (e.g., swelling behavior, biocompatibility, stimuli responsiveness, functionality, etc.) have deemed them ideal platforms for removal of environmental contaminants, detoxification, and reduction of body burden from exogenous chemical exposures for prevention of disease initiation, and advanced treatment of chronic diseases, including cancer, diabetes, and cardiovascular disease. In this review, three main junctures where the use of hydrogel and hydrogel nanocomposite materials can intervene to positively impact human health are highlighted: 1) preventing exposures to environmental contaminants, 2) prophylactic treatments to prevent chronic disease initiation, and 3) treating chronic diseases after they have developed.

show abstract

Section: Treating Diseases Resulting From Chronic Exposure To Environ...mentioning

confidence: 99%

Section: Treating Diseases Resulting From Chronic Exposure To Environ...mentioning

confidence: 99%

Section: Treating Diseases Resulting From Chronic Exposure To Environ...mentioning

confidence: 99%

Section: Treating Cancer With Hydrogels and Hydrogel Nanocompositesmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Hydrogels and Hydrogel Nanocomposites: Enhancing Healthcare through Human and Environmental Treatment

Gutiérrez

Frazar

Klaus

et al. 2021

Adv Healthcare Materials

View full text Add to dashboard Cite

show abstract

In Situ Cocktail Nanovaccine for Cancer Immunotherapy

Liu,

Xie,

et al. 2023

Advanced Science

View full text Add to dashboard Cite

In situ vaccination is a desirable strategy for cancer immunotherapy due to its convenience and capacity to target tumor antigens. Here, an in situ nanovaccine based on a cationic peptide with cholesterol‐modified, DP7‐C, for cancer immunotherapy is rationally designed, and developed a cancer nanovaccine that is easy to preparate. The nanovaccine includes cocktail small interfering RNAs (siRNAs) and immunologic adjuvant CpG ODNs, has synergistic effect in the cancer treatment. This nanovaccine can induce tumor cell death, promote antigen presentation and relieve immune suppression in the tumor microenvironment (TME). Moreover, this nanovaccine is administered to CT26 (hot) and B16F10 (cold) tumor model mice, in which it targeted the primary tumors and induced systemic antitumor immunity to inhibit metastasis. It is validated that the nanovaccine can convert cold tumors into hot tumors. Furthermore, the nanovaccine increased the immune response to anti‐PD‐1 therapy by modulating the TME in both CT26‐ and B16F10‐tumor‐bearing mice. The siRNA cocktail/CpG ODN/self‐assembling peptide nanovaccine is a simple and universal tool that can effectively generate specific tumor cell antigens and can be combined with immuno‐oncology agents to enhance antitumor immune activity. The versatile methodology provides an alternative approach for developing cancer nanovaccines.

show abstract

siRNA delivery from cationic nanocarriers prepared by diffusion‐assisted loading in the presence and absence of electrostatic interactions

Lanier,

D'Andrea,

Shodeinde

et al. 2023

J of Applied Polymer Sci

Self Cite

View full text Add to dashboard Cite

In this study, we use modified cationic nanocarriers as vehicles for the intracellular delivery of therapeutic siRNA. After developing nanocarrier formulations with appropriate pKa, size, swellability, and cytocompatibility, we investigated the importance of siRNA loading methods by studying the impact of the pH and time over which siRNA is loaded into the nanocarriers. We concentrate on diffusion‐based loading in the presence and absence of electrostatic interactions. siRNA release kinetics were studied using samples prepared from nanocarriers loaded by both mechanisms. In addition, siRNA delivery was evaluated for two formulations. While previous studies were conducted with samples prepared by siRNA loading at low pH values, this research provides evidence that loading conditions of siRNA affect the release behavior. This study concludes that this concept could prove advantageous for eliciting prolonged intracellular release of nucleic acids and negatively charged molecules, effectively decreasing dose frequency and contributing to more effective therapies and improved patient outcomes. In addition, our findings could be leveraged for enhanced control over siRNA release kinetics, providing novel methods for the continued optimization of cationic nanoparticles in a wide array of RNA interference‐based applications.

show abstract

Cytocompatibility, membrane disruption, and siRNA delivery using environmentally responsive cationic nanogels

Cited by 14 publications

References 29 publications

Hydrogels and Hydrogel Nanocomposites: Enhancing Healthcare through Human and Environmental Treatment

Hydrogels and Hydrogel Nanocomposites: Enhancing Healthcare through Human and Environmental Treatment

In Situ Cocktail Nanovaccine for Cancer Immunotherapy

siRNA delivery from cationic nanocarriers prepared by diffusion‐assisted loading in the presence and absence of electrostatic interactions

Contact Info

Product

Resources

About