A Nanoparticle Vaccine Displaying Conserved Epitopes of the Preexisting Neutralizing Antibody Confers Broad Protection against SARS-CoV-2 Variants DOI

Xuefan Wu,

Wei Li,

Heng Rong

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(27), P. 17749 - 17763

Published: June 27, 2024

The rapid development of the SARS-CoV-2 vaccine has been used to prevent spread coronavirus 2019 (COVID-19). However, ongoing and future pandemics caused by variants mutations underscore need for effective vaccines that provide broad-spectrum protection. Here, we developed a nanoparticle with broad protection against divergent variants. corresponding conserved epitopes preexisting neutralizing (CePn) antibody were presented on self-assembling Helicobacter pylori ferritin generate CePnF nanoparticle. Intranasal immunization mice nanoparticles induced robust humoral, cellular, mucosal immune responses long-lasting immunity. CePnF-induced antibodies exhibited cross-reactivity activity different coronaviruses (CoVs). vaccination significantly inhibited replication pathology Delta, WIV04, Omicron strains in hACE2 transgenic and, thus, conferred these Our constructed nanovaccine targeting can serve as promising candidate universal vaccine.

Language: Английский

Accelerating ionizable lipid discovery for mRNA delivery using machine learning and combinatorial chemistry DOI
Bowen Li, Idris O. Raji, Akiva G. R. Gordon

et al.

Nature Materials, Journal Year: 2024, Volume and Issue: 23(7), P. 1002 - 1008

Published: May 13, 2024

Language: Английский

Citations

42

Tumor‐Tailored Ionizable Lipid Nanoparticles Facilitate IL‐12 Circular RNA Delivery for Enhanced Lung Cancer Immunotherapy DOI

Shufen Xu,

Yue Xu,

Nicholas C. Solek

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(29)

Published: April 24, 2024

Abstract The advancement of message RNA (mRNA) ‐based immunotherapies for cancer is highly dependent on the effective delivery (Ribonucleic) payloads using ionizable lipid nanoparticles (LNPs). However, clinical application these therapies hindered by variable mRNA expression among different types and risk systemic toxicity. transient profile further complicates this issue, necessitating frequent dosing thus increasing potential adverse effects. Addressing challenges, a high‐throughput combinatorial method utilized to synthesize screen LNPs that efficiently deliver circular (circRNA) lung tumors. lead LNP, H1L1A1B3, demonstrates fourfold increase in circRNA transfection efficiency cells over ALC‐0315, industry‐standard LNPs, while providing potent immune activation. A single intratumoral injection H1L1A1B3 loaded with encoding interleukin‐12 (IL‐12), induces robust response Lewis carcinoma model, leading marked tumor regression. Immunological profiling treated tumors reveals substantial increments CD45 + leukocytes enhances infiltration CD8 T cells, underscoring ability modulate microenvironment favorably. These results highlight tailored LNP platforms advance drug therapy, broadening prospects immunotherapeutics.

Language: Английский

Citations

24

AGILE platform: a deep learning powered approach to accelerate LNP development for mRNA delivery DOI Creative Commons
Yue Xu,

Shihao Ma,

Haotian Cui

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 26, 2024

Abstract Ionizable lipid nanoparticles (LNPs) are seeing widespread use in mRNA delivery, notably SARS-CoV-2 vaccines. However, the expansion of therapies beyond COVID-19 is impeded by absence LNPs tailored for diverse cell types. In this study, we present AI-Guided Lipid Engineering (AGILE) platform, a synergistic combination deep learning and combinatorial chemistry. AGILE streamlines ionizable development with efficient library design, silico screening via neural networks, adaptability to lines. Using AGILE, rapidly synthesize, evaluate lipids selecting from vast library. Intriguingly, reveals cell-specific preferences lipids, indicating tailoring optimal delivery varying These highlight AGILE’s potential expediting customized LNPs, addressing complex needs clinical practice, thereby broadening scope efficacy therapies.

Language: Английский

Citations

23

mRNA delivery systems for cancer immunotherapy: Lipid nanoparticles and beyond DOI Creative Commons

Mariona Estapé Sentí,

Lucía García del Valle,

Raymond M. Schiffelers

et al.

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 206, P. 115190 - 115190

Published: Feb. 1, 2024

mRNA-based vaccines are emerging as a promising alternative to standard cancer treatments and the conventional vaccines. Moreover, FDA-approval of three nucleic acid based therapeutics (Onpattro, BNT162b2 mRNA-1273) has further increased interest trust on this type therapeutics. In order achieve significant therapeutic efficacy, mRNA needs from drug delivery system. last years, several platforms have been explored, being lipid nanoparticles (LNPs) most well characterized studied. A better understanding how operate (both itself system) will help improve their efficacy safety. review, we provide an overview what mode action highlight advantages challenges different that under investigation.

Language: Английский

Citations

22

Rational design of ICD-inducing nanoparticles for cancer immunotherapy DOI Creative Commons
Zhanzhan Zhang, Zheng Pan, Qiushi Li

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(6)

Published: Feb. 7, 2024

Nanoparticle-based cancer immunotherapy has shown promising therapeutic potential in clinical settings. However, current research mainly uses nanoparticles as delivery vehicles but overlooks their to directly modulate immune responses. Inspired by the endogenous endoplasmic reticulum (ER) stress caused unfolded/misfolded proteins, we present a rationally designed immunogenic cell death (ICD) inducer named NanoICD, which is nanoparticle engineered for ER targeting and retention. By carefully controlling surface composition properties, have obtained NanoICD that can effectively accumulate ER, induce stress, activate ICD-associated In addition, generally applicable various proteins enzymes further enhance immunomodulatory capacity, exemplified encapsulating catalase (CAT) obtain NanoICD/CAT, alleviated immunosuppressive tumor microenvironment induced robust antitumor responses 4T1-bearing mice. This work demonstrates nanostructures' autonomously regulate biological processes provides insights into development of advanced nanomedicines treatment.

Language: Английский

Citations

21

Interactions between nanoparticles and lymphatic systems: Mechanisms and applications in drug delivery DOI
Yisi Tang,

Bao Liu,

Yuting Zhang

et al.

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 209, P. 115304 - 115304

Published: April 9, 2024

Language: Английский

Citations

19

Influence of ionizable lipid tail length on lipid nanoparticle delivery of mRNA of varying length DOI Creative Commons
Kaitlin Mrksich, Marshall S. Padilla, Ryann A. Joseph

et al.

Journal of Biomedical Materials Research Part A, Journal Year: 2024, Volume and Issue: 112(9), P. 1494 - 1505

Published: March 15, 2024

RNA-based therapeutics have gained traction for the prevention and treatment of a variety diseases. However, their fragility immunogenicity necessitate drug carrier. Lipid nanoparticles (LNPs) emerged as predominant delivery vehicle RNA therapeutics. An important component LNPs is ionizable lipid (IL), which protonated in acidic environment endosome, prompting cargo release into cytosol. Currently, there growing evidence that structure IL tails significantly impacts efficacy LNP-mediated mRNA translation. Here, we optimized tail length three different cargos. Using C12-200, gold standard IL, model, designed library ILs with varying lengths evaluated potency vivo. We demonstrated small changes lipophilicity can drastically increase or decrease identified formulated firefly luciferase (1929 base pairs) C10-200, an shorter than enhance liver transfection by over 10-fold. Furthermore, were found to be ideal encapsulating cargos sizes. erythropoietin (EPO), responsible stimulating red blood cell production, (858 pairs), C13-200 led EPO translation at levels similar C12-200 LNP. The Cas9 (4521 C9-200 induced times quantity indels compared Our findings suggest may lead higher larger mRNAs, longer more efficacious delivering smaller envision results this project utilized future design criteria next generation LNP systems

Language: Английский

Citations

17

Emerging Delivery Systems for Enabling Precision Nucleic Acid Therapeutics DOI

Xiaochun Bian,

Liping Zhou,

Zhiwei Luo

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Nucleic acid therapeutics represent a highly promising treatment approach in modern medicine, treating diseases at the genetic level. However, these face numerous challenges practical applications, particularly regarding their stability, effectiveness, cellular uptake efficiency, and limitations delivering them specifically to target tissues. To overcome obstacles, researchers have developed various innovative delivery systems, including viral vectors, lipid nanoparticles, polymer inorganic protein carriers, exosomes, antibody oligonucleotide conjugates, DNA nanostructure-based systems. These systems enhance therapeutic efficacy of nucleic drugs by improving targeting specificity, half-life vivo. In this review, we systematically discuss different types drugs, analyze major barriers encountered delivery, summarize current research progress emerging We also highlight latest advancements application for diseases, infectious cancer, brain wound healing. This review aims provide comprehensive overview drug systems' status future directions integrating nanotechnology, biomaterials science, gene editing technologies, emphasizing transformative potential precision medicine.

Language: Английский

Citations

2

Targeted delivery systems of siRNA based on ionizable lipid nanoparticles and cationic polymer vectors DOI
Zhao Yao,

Taiqing Liu,

Jingwen Wang

et al.

Biotechnology Advances, Journal Year: 2025, Volume and Issue: 81, P. 108546 - 108546

Published: Feb. 26, 2025

Language: Английский

Citations

2

Emerging delivery approaches for targeted pulmonary fibrosis treatment DOI Creative Commons
Rimpy Diwan, Himanshu Bhatt,

Elfa Beaven

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 204, P. 115147 - 115147

Published: Dec. 6, 2023

Language: Английский

Citations

25