Enhanced Local Delivery of Engineered IL-2 mRNA by Porous Silica Nanoparticles to Promote Effective Antitumor Immunity

Shin, Hojeong; Kang, Seounghun; Won, Cheolhee; Min, Dal-Hee

doi:10.1021/acsnano.3c06733

Cited by 15 publications

(2 citation statements)

References 55 publications

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“…53,54 Other examples of reported nanoparticles for mRNA include inorganic nanoparticles, such as gold or silica nanoparticles, hybrid nanoparticles, virus-like nanoparticles and peptide-based nanoparticles. 55–58 They are extensively reviewed elsewhere.…”

Section: Introductionmentioning

confidence: 99%

Pseudouridine and N1-methylpseudouridine as potent nucleotide analogues for RNA therapy and vaccine development

Ho,

Schiess,

Miranda

et al. 2024

RSC Chem. Biol.

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Section: Introductionmentioning

confidence: 99%

Pseudouridine and N1-methylpseudouridine as potent nucleotide analogues for RNA therapy and vaccine development

Ho,

Schiess,

Miranda

et al. 2024

RSC Chem. Biol.

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“…This mRNA DDS is based on polyethylenimine-modified porous silica nanoparticles. It promotes effective antitumor immunity without evidence of systemic toxicity and off-target translation of mRNA [ 105 ]. It also inhibited distant metastatic tumors and improved anti-tumor responses in murine cancer models.…”

Section: Introductionmentioning

confidence: 99%

Adjuvants for cancer mRNA vaccines in the era of nanotechnology: strategies, applications, and future directions

Cao,

Yu,

et al. 2024

J Nanobiotechnol

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Research into mRNA vaccines is advancing rapidly, with proven efficacy against coronavirus disease 2019 and promising therapeutic potential against a variety of solid tumors. Adjuvants, critical components of mRNA vaccines, significantly enhance vaccine effectiveness and are integral to numerous mRNA vaccine formulations. However, the development and selection of adjuvant platforms are still in their nascent stages, and the mechanisms of many adjuvants remain poorly understood. Additionally, the immunostimulatory capabilities of certain novel drug delivery systems (DDS) challenge the traditional definition of adjuvants, suggesting that a revision of this concept is necessary. This review offers a comprehensive exploration of the mechanisms and applications of adjuvants and self-adjuvant DDS. It thoroughly addresses existing issues mentioned above and details three main challenges of immune-related adverse event, unclear mechanisms, and unsatisfactory outcomes in old age group in the design and practical application of cancer mRNA vaccine adjuvants. Ultimately, this review proposes three optimization strategies which consists of exploring the mechanisms of adjuvant, optimizing DDS, and improving route of administration to improve effectiveness and application of adjuvants and self-adjuvant DDS.

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A Single‐Dose mRNA Vaccine Employing Porous Silica Nanoparticles Induces Robust Immune Responses Against the Zika Virus

Shin,

Kang,

Won

et al. 2024

Advanced Science

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Recently, lipid nanoparticles (LNPs)‐based mRNA delivery has been approved by the FDA for SARS‐CoV‐2 vaccines. However, there are still considerable points for improvement in LNPs. Especially, local administration of LNPs‐formulated mRNA can cause off‐target translation of mRNA in distal organs which can induce unintended adverse effects. With the hypothesis that large and rigid nanoparticles can be applied to enhance retention of nanoparticles at the injection site, a polyethyleneimine (PEI)‐coated porous silica nanoparticles (PPSNs)‐based mRNA delivery platform is designed. PPSNs not only facilitate localized translation of mRNA at the site of injection but also prolonged protein expression. It is further demonstrated that the development of a highly efficacious Zika virus (ZIKV) vaccine using mRNA encoding full‐length ZIKV pre‐membrane (prM) and envelope (E) protein delivered by PPSNs. The ZIKV prME mRNA‐loaded PPSNs vaccine elicits robust immune responses, including high levels of neutralizing antibodies and ZIKV E‐specific T cell responses in C57BL/6 mice. Moreover, a single injection of prME‐PPSNs vaccine provided complete protection against the ZIKV challenge in mice.

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Enhanced Local Delivery of Engineered IL-2 mRNA by Porous Silica Nanoparticles to Promote Effective Antitumor Immunity

Cited by 15 publications

References 55 publications

Pseudouridine and N1-methylpseudouridine as potent nucleotide analogues for RNA therapy and vaccine development

Pseudouridine and N1-methylpseudouridine as potent nucleotide analogues for RNA therapy and vaccine development

Adjuvants for cancer mRNA vaccines in the era of nanotechnology: strategies, applications, and future directions

A Single‐Dose mRNA Vaccine Employing Porous Silica Nanoparticles Induces Robust Immune Responses Against the Zika Virus

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