From structural design to delivery: mRNA therapeutics for cancer immunotherapy

Exploration, Год журнала: 2023, Номер 4(2)

Опубликована: Ноя. 17, 2023

Abstract mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority expressing all sequence‐known proteins vivo. In particular, a small dosage of delivered mRNA, antigen‐presenting cells (APCs) can synthesize mutant neo‐antigens and multi‐antigens present epitopes to T lymphocytes elicit antitumor effects. addition, receptors like chimeric antigen receptor (CAR), T‐cell (TCR), CD134, immune‐modulating factors including cytokines, interferons, antibodies specific enhance immunological response against tumors. With the maturation vitro transcription (IVT) technology, large‐scale pure encoding be synthesized quickly. However, clinical translation mRNA‐based anticancer strategies is restricted by delivering into target organs or inadequate endosomal escape efficiency mRNA. Recently, there been some advances immunotherapy, which roughly classified modifications structure development delivery systems, especially lipid nanoparticle platforms. this review, latest overcoming limitations immunotherapies recent are summarized. Challenges opportunities applications also discussed.

Язык: Английский

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Lipid Nanoparticles as Promising Carriers for mRNA Vaccines for Viral Lung Infections

Pharmaceutics, Год журнала: 2023, Номер 15(4), С. 1127 - 1127

Опубликована: Апрель 3, 2023

In recent years, there has been an increase in deaths due to infectious diseases, most notably the context of viral respiratory pathogens. Consequently, focus shifted search for new therapies, with attention being drawn use nanoparticles mRNA vaccines targeted delivery improve efficacy these vaccines. Notably, vaccine technologies denote as a era vaccination their rapid, potentially inexpensive, and scalable development. Although they do not pose risk integration into genome are produced from elements, challenges, including exposing naked mRNAs extracellular endonucleases. Therefore, development nanotechnology, we can further efficacy. Nanoparticles, nanometer dimensions, move more freely body and, small size, have unique physical chemical properties. The best candidates transfer lipid (LNPs), which stable biocompatible contain four components: cationic lipids, ionizable polyethylene glycols (PEGs), cholesterol, used facilitate cytoplasmic delivery. this article, components system mRNA-LNP against lung infections such influenza, coronavirus, syncytial virus reviewed. Moreover, provide succinct overview current challenges potential future directions field.

Язык: Английский

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Nanoparticle technology for mRNA: Delivery strategy, clinical application and developmental landscape

Theranostics, Год журнала: 2024, Номер 14(2), С. 738 - 760

Опубликована: Янв. 1, 2024

The mRNA vaccine, a groundbreaking advancement in the field of immunology, has garnered international recognition by being awarded prestigious Nobel Prize, which emerged as promising prophylactic and therapeutic modality for various diseases, especially cancer, rare disease, infectious disease such COVID-19, wherein successful treatment can be achieved improving stability introducing safe effective delivery system. Nanotechnology-based systems, lipid nanoparticles, lipoplexes, polyplexes, lipid-polymer hybrid nanoparticles others, have attracted great interest been explored delivery. Nanoscale platforms protect from extracellular degradation while promoting endosome escape after endocytosis, hence efficacy. This review provides an overview diverse nanoplatforms utilized preclinical clinical stages, including formulation, preparation process, transfection efficiency, administration route. Furthermore, market situation prospects vaccines are discussed here.

Язык: Английский

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Exosome for mRNA delivery: strategies and therapeutic applications

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 4, 2024

Abstract Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, effective delivery vehicles to preserve the cargo from degradation prevent immunogenicity. Exosomes have gained growing attention because of their good biocompatibility, low immunogenicity, small size, unique capacity traverse physiological barriers, cell-specific tropism. Moreover, these exosomes can engineered utilize natural carriers target specific cells or tissues. This targeted approach will enhance efficacy reduce side effects mRNAs. However, difficulties such lack consistent reliable methods for exosome purification efficient encapsulation large mRNAs addressed. article outlines current breakthroughs cell-derived vesicle-mediated its biomedical applications. Graphical

Язык: Английский

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Polymeric and lipid nanoparticles for delivery of self-amplifying RNA vaccines

Journal of Controlled Release, Год журнала: 2021, Номер 338, С. 201 - 210

Опубликована: Авг. 18, 2021

Self-amplifying RNA (saRNA) is a next-generation vaccine platform, but like all nucleic acids, requires delivery vehicle to promote cellular uptake and protect the saRNA from degradation. To date, platforms for have included lipid nanoparticles (LNP), polyplexes cationic nanoemulsions; of these LNP are most clinically advanced with recent FDA approval COVID-19 based-modified mRNA vaccines. While effect on immunogenicity well studied, role biomaterials in effectiveness under investigated. Here, we tested formulated either pABOL, bioreducible polymer, or LNP, characterized protein expression both platforms. We observed that pABOL-formulated resulted higher magnitude expression, formulations were overall more immunogenic. Furthermore, helper phospholipid route administration (intramuscular versus intranasal) impacted two model antigens (influenza hemagglutinin SARS-CoV-2 spike protein). administered intramuscularly, not pABOL intranasally, increased acute interleukin-6 after vaccination. Overall, results indicate systems routes may fulfill different niches within field genetic medicines.

Язык: Английский

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Gold-Nanostar-Chitosan-Mediated Delivery of SARS-CoV-2 DNA Vaccine for Respiratory Mucosal Immunization: Development and Proof-of-Principle

ACS Nano, Год журнала: 2021, Номер 15(11), С. 17582 - 17601

Опубликована: Окт. 27, 2021

The COVID-19 pandemic is caused by the coronavirus SARS-CoV-2 (SC2). A variety of anti-SC2 vaccines have been approved for human applications, including those using messenger RNA (mRNA), adenoviruses expressing SC2 spike (S) protein, and inactivated virus. protective periods immunization afforded these intramuscularly administered are currently unknown. An alternative self-administrable vaccine capable mounting long-lasting immunity via sterilizing neutralizing antibodies would be hugely advantageous in tackling emerging mutant variants. This could also diminish possibility vaccinated individuals acting as passive carriers COVID-19. Here, we investigate potential an intranasal (IN)-delivered DNA encoding S protein BALB/c C57BL/6J immunocompetent mouse models. immune response to IN delivery this SC2-spike transported on a modified gold-chitosan nanocarrier shows strong consistent surge (IgG, IgA, IgM) effective neutralization pseudoviruses proteins different variants (Wuhan, beta, D614G). Immunophenotyping histological analyses reveal chronological events involved recognition antigen resident dendritic cells alveolar macrophages, which prime draining lymph nodes spleen peak SC2-specific cellular humoral responses. attainable high levels IgA lung mucosa tissue-resident memory T can efficiently inhibit its at site entry provide immunity.

Язык: Английский

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Application of microneedle patches for drug delivery; doorstep to novel therapies

Journal of Tissue Engineering, Год журнала: 2022, Номер 13

Опубликована: Янв. 1, 2022

In the past decade, microneedle-based drug delivery systems showed promising approaches to become suitable and alternative for hypodermic injections can control agent without side effects compared conventional approaches. Despite these advantages, procedure of microfabrication is facing some difficulties. For instance, loading method, stability drugs, retention time are subjects debate. Besides, application novel refining fabrication methods, types materials, instruments other issues that need further attention. Herein, we tried summarize recent achievements in controllable (microneedle patches) vitro vivo settings. addition, discussed influence delivered drugs on cellular mechanism immunization molecular signaling pathways through intradermal route. Understanding putative efficiency microneedle patches human medicine help us develop design sophisticated therapeutic modalities.

Язык: Английский

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Advances in Nanoparticles for Effective Delivery of RNA Therapeutics

BioChip Journal, Год журнала: 2022, Номер 16(2), С. 128 - 145

Опубликована: Март 3, 2022

Язык: Английский

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Enzyme-Catalyzed One-Step Synthesis of Ionizable Cationic Lipids for Lipid Nanoparticle-Based mRNA COVID-19 Vaccines

ACS Nano, Год журнала: 2022, Номер 16(11), С. 18936 - 18950

Опубликована: Окт. 21, 2022

Ionizable cationic lipid-containing lipid nanoparticles (LNPs) are the most clinically advanced non-viral gene delivery platforms, holding great potential for therapeutics. This is exemplified by two COVID-19 vaccines employing mRNA-LNP technology from Pfizer/BioNTech and Moderna. Herein, we develop a chemical library of ionizable lipids through one-step chemical-biological enzyme-catalyzed esterification method, synthesized were further prepared to be LNPs mRNA delivery. Through orthogonal design experiment methodology screening, top-performing AA3-DLin show outstanding efficacy long-term storage capability. Furthermore, LNP encapsulating SARS-CoV-2 spike mRNAs successfully induced strong immunogenicity in BALB/c mouse model demonstrated antibody titers, virus challenge, T cell immune response studies. The developed an excellent platform, this study provides overall perspective lipids, aspects design, synthesis, optimization, fabrication, characterization, application.

Язык: Английский

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Advances in the polymeric delivery of nucleic acid vaccines

Theranostics, Год журнала: 2022, Номер 12(9), С. 4081 - 4109

Опубликована: Янв. 1, 2022

Nucleic acid vaccines, especially messenger RNA (mRNA) display unique benefits in the current COVID-19 pandemic.The application of polymeric materials as delivery carriers has greatly promoted nucleic vaccine a promising prophylactic and therapeutic strategy.The inherent properties render vaccines with excellent vivo stability, enhanced biosafety, specific cellular uptake, endolysosomal escape, antigen expression.Although progressed significantly past decades, clinical translation polymer-gene systems still faces insurmountable challenges.This review summarizes diverse polymers their characterizations representative formulations for delivery.We also discussed existing problems, coping strategies, prospect relevant to applications carriers.This highlights rational design development towards meeting goals defending serious or emerging diseases.

Язык: Английский

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