Emerging vaccine nanotechnology: From defense against infection to sniping cancer DOI Creative Commons

Chan Feng,

Yongjiang Li, Bijan Emiliano Ferdows

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(5), P. 2206 - 2223

Published: Jan. 4, 2022

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing human immune system. During ongoing coronavirus disease 2019 (COVID-19) pandemic, still most effective defense modality. The successful clinical application lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages lymph node accumulation, antigen assembly, presentation; they also have, unique pathogen biomimicry properties because well-organized combination multiple factors. Beyond infectious diseases, exhibits considerable potential for cancer treatment. ultimate goal fully mobilize potency system as a living therapeutic recognize tumor antigens eliminate cells, nanotechnologies requisite realize this goal. In review, we summarize recent advances from prevention immunotherapy highlight different types materials, mechanisms, administration methods, well perspectives.

Language: Английский

The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory DOI Creative Commons

Sonia Ndeupen,

Zhen Qin,

Sonya Jacobsen

et al.

iScience, Journal Year: 2021, Volume and Issue: 24(12), P. 103479 - 103479

Published: Nov. 20, 2021

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels side effects. However, the drivers reported effects remain poorly defined. Here we evidence that Acuitas' LNPs in preclinical nucleoside-modified mRNA vaccine studies highly inflammatory mice. Intradermal intramuscular injection these led to rapid robust responses, characterized massive neutrophil infiltration, activation diverse pathways, production various cytokines chemokines. The same dose LNP delivered intranasally similar responses lung resulted high mortality rate, mechanism unresolved. Thus, mRNA-LNP platforms' potency supporting induction adaptive immune observed may stem from LNPs' nature.

Language: Английский

Citations

401
Self-assembled mRNA vaccines DOI Open Access
Jeonghwan Kim, Yulia Eygeris, Mohit Gupta

et al.

Advanced Drug Delivery Reviews, Journal Year: 2021, Volume and Issue: 170, P. 83 - 112

Published: Jan. 2, 2021

Language: Английский

Citations

383
Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines DOI Creative Commons
Thai Thanh Hoang Thi, Estelle J. A. Suys, Jung Seok Lee

et al.

Vaccines, Journal Year: 2021, Volume and Issue: 9(4), P. 359 - 359

Published: April 8, 2021

COVID-19 vaccines have been developed with unprecedented speed which would not possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles played a pivotal role in the successes and many other nanomedicines, such as Doxil

Language: Английский

Citations

369
Vaccine adjuvants: mechanisms and platforms DOI Creative Commons
Tingmei Zhao,

Yulong Cai,

Yujie Jiang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 19, 2023

Abstract Adjuvants are indispensable components of vaccines. Despite being widely used in vaccines, their action mechanisms not yet clear. With a greater understanding the by which innate immune response controls antigen-specific response, adjuvants’ beginning to be elucidated. can categorized as immunostimulants and delivery systems. Immunostimulants danger signal molecules that lead maturation activation antigen-presenting cells (APCs) targeting Toll-like receptors (TLRs) other pattern recognition (PRRs) promote production antigen signals co-stimulatory signals, turn enhance adaptive responses. On hand, systems carrier materials facilitate presentation prolonging bioavailability loaded antigens, well antigens lymph nodes or APCs. The systematically summarized at this review. This is followed an introduction mechanisms, properties, progress classical vaccine adjuvants. Furthermore, since some adjuvants under investigation exhibit potency than adjuvants, could compensate for deficiencies summary adjuvant platforms subsequently presented. Notably, we highlight different immunological properties these platforms, will provide wide range options rational design basis, review points out development prospects problems should paid attention future.

Language: Английский

Citations

342
mRNA vaccine: a potential therapeutic strategy DOI Creative Commons
Yang Wang, Ziqi Zhang, Jingwen Luo

et al.

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Feb. 16, 2021

Abstract mRNA vaccines have tremendous potential to fight against cancer and viral diseases due superiorities in safety, efficacy industrial production. In recent decades, we witnessed the development of different kinds mRNAs by sequence optimization overcome disadvantage excessive immunogenicity, instability inefficiency. Based on immunological study, are coupled with immunologic adjuvant various delivery strategies. Except for optimization, assistance mRNA-delivering strategies is another method stabilize improve their efficacy. The understanding increasing antigen reactiveness gains insight into mRNA-induced innate immunity adaptive without antibody-dependent enhancement activity. Therefore, address problem, scientists further exploited carrier-based (lipid-based delivery, polymer-based peptide-based virus-like replicon particle cationic nanoemulsion), naked dendritic cells-based vaccines. article will discuss molecular biology underlying anti-virus anti-tumor mechanisms, an introduction phenomena, strategies, importance Corona Virus Disease 2019 (COVID-19) related clinical trials diseases. Finally, challenge bacterial parasitic

Language: Английский

Citations

311
Unlocking the promise of mRNA therapeutics DOI Open Access
Eduarde Rohner, Ran Yang, Kylie S. Foo

et al.

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 40(11), P. 1586 - 1600

Published: Nov. 1, 2022

Language: Английский

Citations

306
Passive, active and endogenous organ-targeted lipid and polymer nanoparticles for delivery of genetic drugs DOI Open Access
Sean A. Dilliard, Daniel J. Siegwart

Nature Reviews Materials, Journal Year: 2023, Volume and Issue: 8(4), P. 282 - 300

Published: Jan. 19, 2023

Language: Английский

Citations

304
Apolipoprotein E Binding Drives Structural and Compositional Rearrangement of mRNA-Containing Lipid Nanoparticles DOI Creative Commons
Federica Sebastiani, Marianna Yanez Arteta,

Michael Lerche

et al.

ACS Nano, Journal Year: 2021, Volume and Issue: 15(4), P. 6709 - 6722

Published: March 23, 2021

Emerging therapeutic treatments based on the production of proteins by delivering mRNA have become increasingly important in recent times. While lipid nanoparticles (LNPs) are approved vehicles for small interfering RNA delivery, there still challenges to use this formulation delivery. LNPs typically a mixture cationic lipid, distearoylphosphatidylcholine (DSPC), cholesterol, and PEG-lipid. The structural characterization mRNA-containing (mRNA-LNPs) is crucial full understanding way which they function, but information alone not enough predict their fate upon entering bloodstream. biodistribution cellular uptake affected surface composition as well extracellular present at site LNP administration,

Language: Английский

Citations

249
Cytosolic delivery of nucleic acids: The case of ionizable lipid nanoparticles DOI Creative Commons
Michele Schlich, Roberto Palomba, Gabriella Costabile

et al.

Bioengineering & Translational Medicine, Journal Year: 2021, Volume and Issue: 6(2)

Published: Feb. 3, 2021

Abstract Ionizable lipid nanoparticles (LNPs) are the most clinically advanced nano‐delivery system for therapeutic nucleic acids. The great effort put in development of ionizable lipids with increased vivo potency brought LNPs from laboratory benches to FDA approval patisiran 2018 and ongoing clinical trials mRNA‐based vaccines against SARS‐CoV‐2. Despite these success stories, several challenges remain RNA delivery, including what is known as “endosomal escape.” Reaching cytosol mandatory unleashing activity molecules, their accumulation other intracellular compartments would simply result efficacy loss. In LNPs, ability form destabilizing non‐bilayer structures at acidic pH recognized key endosomal escape cytosolic delivery. This motivating a surge studies aiming designing novel improved biodegradation safety profiles. this work, we describe journey RNA‐loaded across multiple barriers, extracellular space cytosol. silico molecular dynamics modeling, vitro high‐resolution microscopy analyses, imaging data systematically reviewed distill out regulating mechanisms underlying RNA. Finally, comparison strategies employed by enveloped viruses deliver genetic material into cells also presented. combination multidisciplinary analytical toolkit quantification nature‐inspired design could foster future delivery

Language: Английский

Citations

237
Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics DOI Creative Commons

Carla B. Roces,

Gustavo Lou,

Nikita Jain

et al.

Pharmaceutics, Journal Year: 2020, Volume and Issue: 12(11), P. 1095 - 1095

Published: Nov. 15, 2020

In the recent of years, use lipid nanoparticles (LNPs) for RNA delivery has gained considerable attention, with a large number in clinical pipeline as vaccine candidates or to treat wide range diseases. Microfluidics offers advantages their manufacture due its scalability, reproducibility and fast preparation. Thus, this study, we have evaluated operating formulation parameters be considered when developing LNPs. Among them, flow rate ratio (FRR) total (TFR) been shown significantly influence physicochemical characteristics produced particles. particular, increasing TFR FRR decreased particle size. The amino choice (cationic—DOTAP DDAB; ionisable—MC3), buffer (citrate pH 6 TRIS 7.4) type nucleic acid payload (PolyA, ssDNA mRNA) also an impact on these LNPs were high (>90%) loading all cases below 100 nm low polydispersity index (≤0.25). results within paper could used guide development scalable LNP systems using microfluidics.

Language: Английский

Citations

210