Developing mRNA Nanomedicines with Advanced Targeting Functions

Nano-Micro Letters, Год журнала: 2025, Номер 17(1)

Опубликована: Фев. 21, 2025

The emerging messenger RNA (mRNA) nanomedicines have sprung up for disease treatment. Developing targeted mRNA has become a thrilling research hotspot in recent years, as they can be precisely delivered to specific organs or tissues enhance efficiency and avoid side effects. Herein, we give comprehensive review on the latest progress of with targeting functions. its carriers are first described detail. Then, mechanisms passive targeting, endogenous active outlined, focus various biological barriers that may encounter during vivo delivery. Next, emphasis is placed summarizing mRNA-based organ-targeting strategies. Lastly, advantages challenges clinical translation mentioned. This expected inspire researchers this field drive further development technology.

Язык: Английский

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Precision Nanovaccines for Potent Vaccination

JACS Au, Год журнала: 2024, Номер 4(8), С. 2792 - 2810

Опубликована: Июль 31, 2024

Compared with traditional vaccines, nanoparticulate vaccines are especially suitable for delivering antigens of proteins, peptides, and nucleic acids facilitating lymph node targeting. Moreover, apart from improving pharmacokinetics safety, assist molecular adjuvants in crossing biological barriers, targeting immune organs antigen-presenting cells (APC), controlled release, cross-presentation. However, the process that stimulates orchestrates response is complicated, involving spatiotemporal interactions multiple cell types, including APCs, B cells, T macrophages. The performance also depends on microenvironments target or tissues different populations. Therefore, it necessary to develop precise accurately regulate vaccine beyond simply pharmacokinetics. This Perspective summarizes highlights role size, shape, surface charge, spatial management antigen adjuvant a precision vaccination regulating distribution, targeting, response. It discusses importance rational design based anatomical immunological microstructure tissues. delivery release nanovaccines should be taken into consideration designing achieving responses. Additionally, shows remodel suppressed tumor environment modulate various responses which essential.

Язык: Английский

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Enhanced mRNA Delivery via Incorporating Hydrophobic Amines into Lipid Nanoparticles

Colloids and Surfaces B Biointerfaces, Год журнала: 2025, Номер 249, С. 114528 - 114528

Опубликована: Янв. 20, 2025

Язык: Английский

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Multicomponent reaction-based combinatorial chemistry for accelerating the discovery of therapeutic protein and nucleic acid delivery materials

NPG Asia Materials, Год журнала: 2025, Номер 17(1)

Опубликована: Апрель 4, 2025

Язык: Английский

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A Metabolite Co-Delivery Strategy to Improve mRNA Lipid Nanoparticle Delivery

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Lipid nanoparticles (LNPs) effectively protect mRNA and facilitate its entry into target cells for protein synthesis. Despite these successes, cellular alone may not be enough optimal expression, as translation also depends on the availability of essential metabolites, including metabolic energy sources, coenzymes, amino acids. Without adequate less efficient, potentially leading to higher dosing requirements or poorer therapeutic outcomes LNP therapies. To address this, we develop a metabolite co-delivery strategy by encapsulating metabolites within LNPs, hypothesizing that our approach can uniformly improve delivery. Instead adding fifth component organic phase, involves mixing with payload in aqueous while maintaining molar ratio components phase during formulation. We verify vitro vivo, highlighting broad applicability through mechanism efficacy studies across multiple cell lines, physiological conditions, such normoxia (i.e., 21% oxygen), hypoxia 1% mice. Taken collectively, anticipate serve generalizable enhance vivo expression using offering study treatment disease.

Язык: Английский

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Exaggerated Lung Inflammation Induced by Lung-Targeted mRNA-LNP Dampens Vaccines against Tuberculosis

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Май 16, 2025

The challenges in developing a tuberculosis (TB) vaccine stem from the complex life cycle of Mycobacterium (Mtb) and various bacterial proteins encoded by approximately 4000 genes. mRNA is easy to design can accommodate multiple antigens, suggesting that it may be an effective TB technology. Here, we designed encoding Ag85B ESAT6 was delivered lung targeted lipid nanoparticles (LNPlung-mRNAA-E), intending stimulate immunity combat TB. To enhance efficacy, further cofabricated monophosphoryl A (MPLA) with evaluate adjuvanted (LNPlung-mRNAA-E-MPLA). Both vaccines elicited robust CD4+ T cell response, resulting markedly locally higher production IFN-γ, TNF-α, IL-2. As anticipated, addition MPLA enhanced immunogenicity LNPlung-mRNAA-E. However, Mtb challenge experiment showed LNPlung-mRNAA-E-MPLA neither provided protection nor immune primed BCG (Bacillus Calmette-Guérin). subsequent HE staining revealed induced pulmonary inflammation, leading tissue damage. Moreover, inflammatory cytokines including IL-6, IL-1β, MCP-1 were significantly increased additive exacerbated process. Therefore, adjuvant synergistically inflammation weakened infection. Thus, this work provides valuable implications for vaccines: Addressing chronic systems critical lung-targeted vaccines.

Язык: Английский

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Tertiary amine N-oxide zwitterionic lipids facilitate muscle-selective mRNA vaccine delivery for enhancing cDC1-mediated antitumor efficacy

Journal of Controlled Release, Год журнала: 2025, Номер unknown, С. 113892 - 113892

Опубликована: Май 1, 2025

Язык: Английский

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Incorporation of disulfide bonds into ionizable lipids enables efficient splenic mRNA delivery and potent immunotherapy in mice

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 164285 - 164285

Опубликована: Май 1, 2025

Язык: Английский

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Impact of tail unsaturation in ionizable lipids on mRNA delivery efficiency and immunogenicity of lipid nanoparticles

Journal of Controlled Release, Год журнала: 2025, Номер unknown, С. 113906 - 113906

Опубликована: Июнь 1, 2025

Язык: Английский

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Strategies for Organ‐Targeted mRNA Delivery by Lipid Nanoparticles

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, Год журнала: 2024, Номер 16(5)

Опубликована: Сен. 1, 2024

ABSTRACT Messenger RNA (mRNA) technology has rapidly evolved, significantly impacting various therapeutic applications, including vaccines, protein replacement, and gene editing. Lipid nanoparticles (LNPs) have emerged as a pivotal nonviral vector for mRNA delivery, crucial organ‐targeted therapies. Despite their success, most LNP formulations predominantly target the liver, limiting use in nonliver diseases. This review explores strategies to achieve organ‐specific delivery using LNPs, discovery of new lipid structures, modification targeting ligands, incorporation additional components, optimization formulations. These advancements aim enhance precision efficacy therapeutics across broader range

Язык: Английский

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