Nucleic Acid Conjugates: Unlocking Therapeutic Potential DOI Creative Commons
Disha Kashyap, Michael J. Booth

ACS Bio & Med Chem Au, Journal Year: 2024, Volume and Issue: 5(1), P. 3 - 15

Published: Dec. 18, 2024

Nucleic acids have emerged as a powerful class of therapeutics. Through simple base pair complementarity, nucleic allow the targeting variety pathologically relevant proteins and RNA molecules. However, despite preliminary successes drugs in clinic, limited biodistribution, inadequate delivery mechanisms, target engagement remain key challenges field. A area research has been chemical optimization acid backbones to significantly enhance their "drug-like" properties. Alternatively, this review focuses on next generation modifications: covalent biochemical conjugates. These conjugates are being applied improve delivery, functionality, targeting. Exploiting heterobifunctionals, such PROTACs, RIBOTACs, molecular glues, etc., potential dramatically expand drug functionality capabilities. Such next-generation chemistry-based enhancements unlock effective versatile therapeutic agents.

Language: Английский

Design of PD‐L1‐Targeted Lipid Nanoparticles to Turn on PTEN for Efficient Cancer Therapy DOI Creative Commons
Yelee Kim, Jiwoong Choi, Eun Hye Kim

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(22)

Published: March 23, 2024

Abstract Lipid nanoparticles (LNPs) exhibit remarkable mRNA delivery efficiency, yet their majority accumulate in the liver or spleen after injection. Tissue‐specific can be achieved through modulating LNP properties, such as tuning PEGylation varying lipid components systematically. In this paper, a streamlined method is used for incorporating tumor‐targeting peptides into LNPs; programmed death ligand 1 (PD‐L1) binding are conjugated to PEGylated lipids via copper‐free click reaction, and directly incorporated composition (Pep LNPs). Notably, Pep LNPs display robust interaction with PD‐L1 proteins, which leads uptake of overexpressing cancer cells both vitro vivo. To evaluate anticancer immunotherapy mediated by restoring tumor suppressor, encoding phosphatase tensin homolog (PTEN) delivered PTEN‐deficient triple‐negative breast cancers (TNBCs). loaded PTEN specifically promotes autophagy‐mediated immunogenic cell 4T1 tumors, resulting effective immune responses. This study highlights potential tumor‐targeted mRNA‐based therapy.

Language: Английский

Citations

20
Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach DOI Creative Commons

Ehsan Bitaraf Haghighi,

Samira Sadat Abolmaali, Ali Dehshahri

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 14, 2024

RNA therapeutics, such as mRNA, siRNA, and CRISPR–Cas9, present exciting avenues for treating diverse diseases. However, their potential is commonly hindered by vulnerability to degradation poor cellular uptake, requiring effective delivery systems. Lipid nanoparticles (LNPs) have emerged a leading choice in vivo delivery, offering protection against degradation, enhanced facilitation of endosomal escape. LNPs encounter numerous challenges targeted vivo, demanding advanced particle engineering, surface functionalization with targeting ligands, profound comprehension the biological milieu which they function. This review explores structural physicochemical characteristics LNPs, in-vivo fate, customization therapeutics. We highlight quality-by-design (QbD) approach beyond liver, focusing on biodistribution, immunogenicity, toxicity. In addition, we explored current strategies associated ensuring repeated-dose efficacy, safety, tissue-specific gene delivery. Furthermore, provide insights into clinical applications various classes diseases finally prospects

Language: Английский

Citations

8
Transforming native exosomes to engineered drug vehicles: A smart solution to modern cancer theranostics DOI
Rajeev Kumar Sahoo, Surya Kant Tripathi,

Stuti Biswal

et al.

Biotechnology Journal, Journal Year: 2024, Volume and Issue: 19(2)

Published: Feb. 1, 2024

Abstract Exosomes have been the hidden treasure of cell in terms cellular interactions, transportation and therapy. The native exosomes (NEx) secreted by parent cells hold promising aspects cancer diagnosis NEx has low immunogenicity, high biocompatibility, toxicity stability which enables them to be an ideal prognostic biomarker diagnosis. However, due heterogeneity, lacks specificity accuracy used as therapeutic drug delivery vehicle Transforming these with their innate structure multiple receptors engineered (EEx) can provide better opportunities field theranostics. surface exhibits numeric modified pave direction its Through membrane, EEx increased loading potentiality higher target act a nanocarrier for delivery. This review provides insights into tool along need transformation We also highlighted different methods associated transformations, nano‐bio interaction recipient major challenges clinical application

Language: Английский

Citations

6
Beyond Skin Deep: Phospholipid-Based Nanovesicles as Game-Changers in Transdermal Drug Delivery DOI
Mohamed A. Akl, Muhammad Alaa Eldeen, Abdulsalam M. Kassem

et al.

AAPS PharmSciTech, Journal Year: 2024, Volume and Issue: 25(6)

Published: Aug. 13, 2024

Language: Английский

Citations

6
Influence of polyethylene glycol coating of different molecular weights and densities on liposome properties DOI
Hongjing Chen, Lin Wu, Huali Chen

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2025, Volume and Issue: 106, P. 106725 - 106725

Published: Feb. 18, 2025

Language: Английский

Citations

0
SpyTag/SpyCatcher-ligated nanostructured lipid carriers for active mammary cancer targeting DOI
Min Kyung Sung,

Jin Young Heo,

Seonhye Jang

et al.

Journal of Industrial and Engineering Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0
Peptide‐Based Strategies in PLGA‐Enhanced Tumor Therapy DOI
Haiyan Han,

Jingyun Su,

Xiaodan Zhao

et al.

Journal of Peptide Science, Journal Year: 2025, Volume and Issue: 31(6)

Published: April 23, 2025

ABSTRACT Peptide‐based therapeutics have gained attention in cancer treatment because of their good specificity, low toxicity, and ability to modulate immune responses. However, challenges such as enzymatic degradation poor bioavailability limit clinical application. Peptide‐functionalized poly(lactic‐co‐glycolic acid) (PLGA) systems emerged a transformative platform therapy that offers unique advantages, including enhanced stability, sustained release, precise delivery therapeutic agents. This review highlights the synergistic integration peptides with PLGA addresses key peptide‐based therapeutics. The application peptide‐functionalized encompasses diverse range strategies for therapy. In chemotherapy, disrupt critical tumor pathways, induce apoptosis, inhibit angiogenesis, demonstrating versatility targeting various aspects progression. immunotherapy, act antigens stimulate robust responses or checkpoint inhibitors restore T cell activity, overcoming evasion. These also harness permeability retention effect, facilitating preferential accumulation tissues while leveraging microenvironment (TME)‐responsive mechanisms, pH‐sensitive enzyme‐triggered drug achieve controlled, localized delivery. Collectively, represent promising, versatile approach integrates innovative highly specific, potent

Language: Английский

Citations

0
Composition of lipid nanoparticles for targeted delivery: application to mRNA therapeutics DOI Creative Commons
О. С. Васильева, Olga V. Zaborova,

Bogdan Shmykov

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 23, 2024

Today, lipid nanoparticles (LNPs) are some of the main delivery systems for mRNA-based therapeutics. The scope LNP applications in terms RNA is not limited to antiviral vaccines but encompasses anticancer drugs and therapeutics genetic (including rare) diseases. Such widespread use implies high customizability targeted LNPs specific organs tissues. This review addresses vector-free options LNPs, namely influence composition these on their biodistribution. In review, experimental studies examined that focused biodistribution mRNA or encoded protein after administration via mammals. We also performed a comprehensive analysis individual lipids’ functional groups ensure desired organs. These data will allow us outline prospects further optimization compositions

Language: Английский

Citations

2
Mechanisms of extracellular vesicle uptake and implications for the design of cancer therapeutics DOI Creative Commons
Stephanie R. Jackson, Joseph P. Flemming,

Kübra Karagoz

et al.

Journal of Extracellular Biology, Journal Year: 2024, Volume and Issue: 3(11)

Published: Oct. 30, 2024

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue achieve or seek approval, setbacks are often attributed a lack efficacy, failure clinical endpoints, dose-limiting toxicities. Successful efforts have characterized by the development therapeutics designed specifically deliver optimal dosing tumour cells while minimizing off-target toxicity. Much effort devoted rational design application synthetic nanoparticles serve as targeted therapeutic delivery vehicles. Several challenges successful this modality vehicles include induction protracted immune response that results in their rapid systemic clearance, manufacturing cost, stability, biocompatibility. Extracellular vesicles (EVs) heterogeneous class endogenous biologically produced lipid bilayer mediate intercellular communication carrying bioactive macromolecules capable modifying cellular phenotypes local distant cells. By genetic, chemical, metabolic methods, extracellular can be engineered display targeting moieties on surface transporting specific cargo modulate pathological processes following uptake target cell populations. This review will survey types EVs, composition cargoes, strategies employed increase targeting, uptake, release, potential

Language: Английский

Citations

2
Enhancing non-viral DNA delivery systems: Recent advances in improving efficiency and target specificity DOI Creative Commons
Mahboubeh Hosseini-Kharat, Kristen E. Bremmell, Branka Grubor‐Bauk

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 378, P. 170 - 194

Published: Dec. 12, 2024

DNA-based therapies are often limited by challenges such as stability, long-term integration, low transfection efficiency, and insufficient targeted DNA delivery. This review focuses on recent progress in the design of non-viral delivery systems for enhancing modulation therapeutic efficiency. Cellular uptake intracellular trafficking mechanisms play a crucial role optimizing gene There two main strategies employed to improve efficiency vectors: (i) explore different administration routes (e.g., mucosal, intravenous, intramuscular, subcutaneous, intradermal, intratumoural, intraocular) that best facilitates optimal into cells organs (ii) modify vectors with cell-specific ligands natural ligands, antibodies, peptides, carbohydrates, or aptamers) enable specific higher specificity improved biodistribution. We describe how employing these is advancing field increasing clinical translation ultimate application therapies.

Language: Английский

Citations

1