A nanovaccine for enhancing cellular immunity via cytosolic co-delivery of antigen and polyIC RNA

Carson, Carcia S.; Becker, Kyle W.; Garland, Kyle M.; Pagendarm, Hayden M; Stone, Payton T; Arora, Karan; Wang-Bishop, Lihong; Baljon, Jessalyn J.; Cruz, Lorena D; Joyce, Sebastian; Wilson, John T.

doi:10.1016/j.jconrel.2022.03.020

Cited by 23 publications

(13 citation statements)

References 78 publications

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“…102,103 When cationic polymers with pH-responsive chains enter antigen-presenting cells and respond to the decreased pH in the endosomal compartment, the cationic polymers with positive charges would escape from lysosomes and exert the effectiveness of cationic polymeric nanovaccines. 104 Su et al reported a pHresponsive CDN/neoantigen codelivering nanovaccines to overcome the low patient responsive rates of ICB therapy through combining with ICB. 105,106 In detail, designing cationic poly((2-dimethylaminoethyl) methacrylate) (PDMA) to load the CDN through electrostatic complexation, and PEG as the modification chain on the surface of NPs to enhance the biocompatibility of NPs.…”

Section: Cationic Polymer-based Ph-sensitive Polymericmentioning

confidence: 99%

“…The pH-sensitive polymeric vehicle is capable of self-assembly into nanovaccines and triggered by pH microenvironment in vivo, resulting in controlled therapeutic drug delivery and release for improved therapeutic efficacy. Therefore, based on the pH-responsive design, many cationic polymers modified with pH-responsive chains have been widely researched, such as poly((2-dimethylaminoethyl) methacrylate) (PDMA) and PEI. , When cationic polymers with pH-responsive chains enter antigen-presenting cells and respond to the decreased pH in the endosomal compartment, the cationic polymers with positive charges would escape from lysosomes and exert the effectiveness of cationic polymeric nanovaccines . Su et al reported a pH-responsive CDN/neoantigen codelivering nanovaccines to overcome the low patient responsive rates of ICB therapy through combining with ICB. , In detail, designing cationic poly((2-dimethylaminoethyl) methacrylate) (PDMA) to load the CDN through electrostatic complexation, and PEG as the modification chain on the surface of NPs to enhance the biocompatibility of NPs.…”

Section: Ph-sensitive Polymeric Nanovaccinesmentioning

confidence: 99%

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Stimuli-Responsive Polymeric Nanovaccines Toward Next-Generation Immunotherapy

Mao

Luo

et al. 2023

ACS Nano

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The development of nanovaccines that employ polymeric delivery carriers has garnered substantial interest in therapeutic treatment of cancer and a variety of infectious diseases due to their superior biocompatibility, lower toxicity and reduced immunogenicity. Particularly, stimuli-responsive polymeric nanocarriers show great promise for delivering antigens and adjuvants to targeted immune cells, preventing antigen degradation and clearance, and increasing the uptake of specific antigen-presenting cells, thereby sustaining adaptive immune responses and improving immunotherapy for certain diseases. In this review, the most recent advances in the utilization of stimulus-responsive polymer-based nanovaccines for immunotherapeutic applications are presented. These sophisticated polymeric nanovaccines with diverse functions, aimed at therapeutic administration for disease prevention and immunotherapy, are further classified into several active domains, including pH, temperature, redox, light and ultrasound-sensitive intelligent nanodelivery systems. Finally, the potential strategies for the future design of multifunctional next-generation polymeric nanovaccines by integrating materials science with biological interface are proposed.

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Section: Cationic Polymer-based Ph-sensitive Polymericmentioning

confidence: 99%

Section: Ph-sensitive Polymeric Nanovaccinesmentioning

confidence: 99%

Stimuli-Responsive Polymeric Nanovaccines Toward Next-Generation Immunotherapy

Mao

Luo

et al. 2023

ACS Nano

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“…Importantly, intelligent antigen delivery systems capable of precise cytoplasmic antigen delivery could facilitate the generation of CD8 + CTLs to enhance the antitumor efficacy of tumor vaccines. 18 Recently, porous metalorganic framework (MOF) nanoparticles have attracted considerable attention owing to their ultra-high specific surface area, easy surface modification, excellent biocompatibility, and promising potential to elicit strong immune responses. [19][20][21] However, MOFs prepared using the traditional solution method are restricted by their tiny pore size (<2 nm), which seriously limits their applications in the encapsulation of macromolecular antigen proteins as well as in diffusionlimited processes.…”

Section: Introductionmentioning

confidence: 99%

Macro-microporous ZIF-8 MOF complexed with lysosomal pH-adjusting hexadecylsulfonylfluoride as tumor vaccine delivery systems for improving anti-tumor cellular immunity

Zuo

Huang

et al. 2023

Biomater. Sci.

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“…19 To enable codelivery of antigens with immune-stimulating adjuvants, Wilson et al have utilized stimuli-responsive block copolymers composed of a combination of antigen/adjuvant complexing blocks and pHresponsive, endosomolytic blocks. 20 Their work has led cumulatively to the development of cationic NPs appropriate for local administration (e.g., inhalation), 21 PEGylated micelles, 22 and PEGylated polymersomes capable of cytosolic codelivery of antigens and various adjuvants. 23,24 Here, we introduce a glycopolymeric NP (glycoNP) that is biocompatible, well under 100 nm in diameter, capable of protein complexation, reduction-triggered antigen release, and pH-triggered endosomolysis and adjuvant release.…”

Section: ■ Introductionmentioning

confidence: 99%

“…To enable codelivery of antigens with immune-stimulating adjuvants, Wilson et al have utilized stimuli-responsive block copolymers composed of a combination of antigen/adjuvant complexing blocks and pH-responsive, endosomolytic blocks . Their work has led cumulatively to the development of cationic NPs appropriate for local administration (e.g., inhalation), PEGylated micelles, and PEGylated polymersomes capable of cytosolic codelivery of antigens and various adjuvants. , …”

Section: Introductionmentioning

confidence: 99%

Dual-Responsive Glycopolymers for Intracellular Codelivery of Antigen and Lipophilic Adjuvants

et al. 2022

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Traditional approaches to vaccines use whole organisms to trigger an immune response, but they do not typically generate robust cellular-mediated immunity and have various safety risks. Subunit vaccines composed of proteins and/or peptides represent an attractive and safe alternative to whole organism vaccines, but they are poorly immunogenic. Though there are biological reasons for the poor immunogenicity of proteins and peptides, one other key to their relative lack of immunogenicity could be attributed to the poor pharmacokinetic properties of exogenously delivered proteins and peptides. For instance, peptides often aggregate at the site of injection and are not stable in biological fluids, proteins and peptides are rapidly cleared from circulation, and both have poor cellular internalization and endosomal escape. Herein, we developed a delivery system to address the lack of protein immunogenicity by overcoming delivery barriers as well as codelivering immune-stimulating adjuvants. The glycopolymeric nanoparticles (glycoNPs) are composed of a dual-stimuli-responsive block glycopolymer, poly[2-(diisopropylamino)ethyl methacrylate]-b-poly[(pyridyl disulfide ethyl methacrylate)-co-(methacrylamidoglucopyranose)] (p[DPAb-(PDSMA-co-MAG)]). This polymer facilitates protein conjugation and cytosolic release, the pH-responsive release of lipophilic adjuvants, and pH-dependent membrane disruption to ensure cytosolic delivery of antigens. We synthesized p[DPA-b-(PDSMA-co-MAG)] by reversible addition−fragmentation chain transfer (RAFT) polymerization, followed by the formation and physicochemical characterization of glycoNPs using the p[DPA-b-(PDSMA-co-MAG)] building blocks. These glycoNPs conjugated the model antigen ovalbumin (OVA) and released OVA in response to elevated glutathione levels. Moreover, the glycoNPs displayed pH-dependent drug release of the model hydrophobic drug Nile Red while also exhibiting pH-responsive endosomolytic behavior as indicated by a red blood cell hemolysis assay. GlycoNPs coloaded with OVA and the toll-like receptor 7/8 (TLR-7/8) agonist Resiquimod (R848) activated DC 2.4 dendritic cells (DCs) significantly more than free OVA and R848 and led to robust antigen presentation of the OVA epitope SIINFEKL on major histocompatibility complex I (MHC-I). In sum, the dual-stimuliresponsive glycopolymer introduced here overcomes major protein and peptide delivery barriers and could vastly improve the immunogenicity of protein-based vaccines.

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A nanovaccine for enhancing cellular immunity via cytosolic co-delivery of antigen and polyIC RNA

Cited by 23 publications

References 78 publications

Stimuli-Responsive Polymeric Nanovaccines Toward Next-Generation Immunotherapy

Stimuli-Responsive Polymeric Nanovaccines Toward Next-Generation Immunotherapy

Macro-microporous ZIF-8 MOF complexed with lysosomal pH-adjusting hexadecylsulfonylfluoride as tumor vaccine delivery systems for improving anti-tumor cellular immunity

Dual-Responsive Glycopolymers for Intracellular Codelivery of Antigen and Lipophilic Adjuvants

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