Galloyl Dialkyl Lipids Drive Encapsulation of Peptides into Lipid Nanoparticles by Hydrogen Bonding DOI

Tingting Ye,

Yong Chen, Zifu Zhong

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 147(1), P. 1307 - 1318

Published: Dec. 19, 2024

The intracellular delivery of peptides and proteins is crucial for various biomedical applications. Lipid nanoparticles (LNPs) have emerged as a promising strategy delivering to phagocytic cells. However, the diverse physicochemical properties necessitate tailored formulations. This study introduces generic approach using galloyl (GA)-functionalized lipids encapsulation in LNPs via hydrogen bonding between ubiquitously present amides multivalently displayed phenol groups GA-LNPs. In vitro studies showed that GA-LNPs significantly improved cellular uptake activated immune responses when combined with Toll-like receptor (TLR) agonists MPLA IMDQ. vivo, accumulated spleen enhanced peptide antigen-presenting coencapsulating antigens TLR elicited robust antigen-specific CD8+ T-cell mice.

Language: Английский

Advanced technologies for the development of infectious disease vaccines DOI
Akash Gupta, Arnab Rudra,

Kaelan Reed

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(12), P. 914 - 938

Published: Oct. 21, 2024

Language: Английский

Citations

11
CO-DELIVERY of glutamic acid-extended peptide antigen and imidazoquinoline TLR7/8 agonist via ionizable lipid nanoparticles induces protective anti-tumor immunity DOI

Tingting Ye,

Zifu Zhong, Federica Cappellesso

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 311, P. 122693 - 122693

Published: June 27, 2024

Language: Английский

Citations

7
Intratumoral delivery of lipid nanoparticle-formulated mRNA encoding IL-21, IL-7, and 4-1BBL induces systemic anti-tumor immunity DOI Creative Commons
Ahmed E.I. Hamouda,

Jessica Filtjens,

Elisabeth Brabants

et al.

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

Published: Dec. 5, 2024

Local delivery of mRNA-based immunotherapy offers a promising avenue as it enables the production specific immunomodulatory proteins that can stimulate immune system to recognize and eliminate cancer cells while limiting systemic exposure toxicities. Here, we develop employ lipid-based nanoparticles (LNPs) intratumorally deliver an mRNA mixture encoding cytokines interleukin (IL)−21 IL-7 immunostimulatory molecule 4-1BB ligand (Triplet LNP). IL-21 synergy with 4-1BBL leads profound increase in frequency tumor-infiltrating CD8+ T their capacity produce granzyme B IFN-γ, leading tumor eradication development long-term immunological memory. Mechanistically, efficacy Triplet LNP depends on tumor-draining lymph nodes T-cell trafficking. Moreover, highlight therapeutic potential multiple models female mice its superior checkpoint blockade. Ultimately, expression these immunomodulators is associated better overall survival patients cancer. represents option for therapy. Here authors report intratumoral lipid nanoparticle-formulated IL-21, IL-7, induces anti-tumor immunity preclinical models.

Language: Английский

Citations

4
A Genetically Encoded Endogenous Antibody Recruitment Strategy for Innate Immune‐Mediated Killing of Cancer Cells DOI Open Access

Justine Aelvoet,

Zifu Zhong, C. Gómez

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 9, 2025

Antibody-recruiting molecules (ARMs) are bivalent that contain a cell-binding domain and an antibody-binding domain. ARMs designed to redirect circulating endogenous antibodies from the bloodstream surface of cancer cells thereby trigger innate immune-mediated killing latter. The current generation clinically explored relies on synthetic small molecule haptens. However, their effectiveness is restricted by low affinity available repertoire anti-hapten antibodies. Utilizing high-affinity allergen-specific could potentially circumvent this issue. In study, genetically encoded antibody-recruiting strategy utilizes lipid nanoparticles (LNPs) deliver mRNA encoding house dust mite allergen Der p 2, fused cell membrane anchor, induce display enable recruitment anti-Der 2 antibodies, presented. LNP-treated cause greatly reduced pulmonary tumor burden in immunized mice, compared untreated or nonimmunized mice. Reduced growth dependent neutrophils identified as key immune subset recognizing eliminating 2-displaying cells. These findings emphasize LNPs powerful tool for generating ARM strategy, with potential applications immunotherapy.

Language: Английский

Citations

0
Influence of salt solution on the physicochemical properties and in vitro/ in vivo expression of mRNA/LNP DOI Creative Commons
Siyuan Tang, Lei Huang, Jiahao Ge

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 19, 2025

Lipid nanoparticles (LNPs) have revolutionized nucleic acid delivery, enabling significant advances in mRNA-based therapeutics. While extensive research has focused on lipid composition, the impact of preparation solutions LNP performance remains underexplored. This study systematically investigated effects pH, salt type, and concentration across key solutions—mRNA aqueous, dilution, exchange, storage solutions—on physicochemical properties, stability, expression efficiency SM102-based mRNA/LNPs. Findings revealed that pH mRNA aqueous solution was critical, with a 4 optimizing encapsulation (EE) cellular expression. The exchange solution's significantly influenced biodistribution, particularly liver-specific following intravenous intramuscular administration. Sucrose identified as essential for freeze-thaw 300 mM minimizing aggregation leakage. Furthermore, were shown to influence structural integrity LNPs, impacting their vivo vitro performance. These insights highlight importance conditions formulations clinical applications, offering foundation enhanced therapeutic design delivery.

Language: Английский

Citations

0
Paracyclophane-based ionizable lipids for efficient mRNA delivery in vivo DOI

Shiqi Wu,

Kexin Su, Xinxin Yan

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 376, P. 395 - 401

Published: Oct. 20, 2024

Language: Английский

Citations

3
Stimuli-Responsive Nanomedicines for the Treatment of Non-cancer Related Inflammatory Diseases DOI Creative Commons
Jingjing Yang, Anne des Rieux, Alessio Malfanti

et al.

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

Published: April 18, 2025

Nanomedicines offer a means to overcome the limitations associated with traditional drug dosage formulations by affording protection, enhanced bioavailability, and targeted delivery affected sites. Inflamed tissues possess unique microenvironmental characteristics (including excessive reactive oxygen species, low pH levels, hypoxia) that stimuli-responsive nanoparticles can employ as triggers support on-demand delivery, accumulation, controlled release, activation of anti-inflammatory drugs. Stimuli-responsive nanomedicines respond physicochemical pathological factors diseased improve specificity multidrug resistance, ensure accurate diagnosis precision therapy, control release efficacy safety. Current react intracellular/microenvironmental stimuli such pH, redox, hypoxia, or specific enzymes exogenous temperature, magnetic fields, light, ultrasound via bioresponsive moieties. This review summarizes general strategies employed produce tailored for inflammatory diseases all recent advances, reports their applications in illustrates progress made toward clinical translation.

Language: Английский

Citations

0
A Fentanyl Hapten‐Displaying Lipid Nanoparticle Vaccine that Non‐Covalently Encapsulates a TLR7/8 Agonist and T‐helper Epitope Induces Protective Anti‐Fentanyl Immunity DOI
Zifu Zhong, Marie H. Deventer, Yong Chen

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Abstract Opioid use disorder ‐ particularly involving fentanyl has precipitated a public health crisis characterized by significant increase in addiction and overdose‐related deaths. Fentanyl‐specific immunotherapy, which aims at inducing fentanyl‐specific antibodies capable of binding molecules the bloodstream, preventing their entry central nervous system, is therefore gaining momentum. Conventional opioid designs rely on covalent conjugation analogues to immunogenic carrier proteins that hold inherent capacity mounting immunodominant responses. Here, we present an alternative vaccine design utilizes non‐covalent assembly lipid nanoparticles (LNPs) deliver haptens conjunction with CD4 + T‐helper peptide epitope imidazoquinoline TLR7/8 agonist. Our results demonstrate single intramuscular administration LNP‐based nanovaccine elicits antibodies, significantly mitigating effects overdose preclinical mouse models. Furthermore, analyzed immunobiological behavior vivo models, providing evidence attachment hapten or not necessary for effective immune response. However, co‐delivery specifically, physical all cues into LNP remains essential hapten‐specific immunity.

Language: Английский

Citations

2
A Fentanyl Hapten‐Displaying Lipid Nanoparticle Vaccine that Non‐Covalently Encapsulates a TLR7/8 Agonist and T‐helper Epitope Induces Protective Anti‐Fentanyl Immunity DOI
Zifu Zhong, Marie H. Deventer, Yong Chen

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Abstract Opioid use disorder ‐ particularly involving fentanyl has precipitated a public health crisis characterized by significant increase in addiction and overdose‐related deaths. Fentanyl‐specific immunotherapy, which aims at inducing fentanyl‐specific antibodies capable of binding molecules the bloodstream, preventing their entry central nervous system, is therefore gaining momentum. Conventional opioid designs rely on covalent conjugation analogues to immunogenic carrier proteins that hold inherent capacity mounting immunodominant responses. Here, we present an alternative vaccine design utilizes non‐covalent assembly lipid nanoparticles (LNPs) deliver haptens conjunction with CD4 + T‐helper peptide epitope imidazoquinoline TLR7/8 agonist. Our results demonstrate single intramuscular administration LNP‐based nanovaccine elicits antibodies, significantly mitigating effects overdose preclinical mouse models. Furthermore, analyzed immunobiological behavior vivo models, providing evidence attachment hapten or not necessary for effective immune response. However, co‐delivery specifically, physical all cues into LNP remains essential hapten‐specific immunity.

Language: Английский

Citations

1
Galloyl Dialkyl Lipids Drive Encapsulation of Peptides into Lipid Nanoparticles by Hydrogen Bonding DOI

Tingting Ye,

Yong Chen, Zifu Zhong

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 147(1), P. 1307 - 1318

Published: Dec. 19, 2024

The intracellular delivery of peptides and proteins is crucial for various biomedical applications. Lipid nanoparticles (LNPs) have emerged as a promising strategy delivering to phagocytic cells. However, the diverse physicochemical properties necessitate tailored formulations. This study introduces generic approach using galloyl (GA)-functionalized lipids encapsulation in LNPs via hydrogen bonding between ubiquitously present amides multivalently displayed phenol groups GA-LNPs. In vitro studies showed that GA-LNPs significantly improved cellular uptake activated immune responses when combined with Toll-like receptor (TLR) agonists MPLA IMDQ. vivo, accumulated spleen enhanced peptide antigen-presenting coencapsulating antigens TLR elicited robust antigen-specific CD8+ T-cell mice.

Language: Английский

Citations

0