Development of Lipid Nanoparticle Formulation for the Repeated Administration of mRNA Therapeutics DOI Creative Commons
Yeji Lee, Michaela Jeong, Gyeongseok Lee

et al.

Biomaterials Research, Journal Year: 2024, Volume and Issue: 28

Published: Jan. 1, 2024

During the COVID-19 pandemic, mRNA vaccines emerged as a rapid and effective solution for global immunization. The success of has increased interest in use lipid nanoparticles (LNPs) vivo delivery therapeutics. Although exhibits robust expression profiles, transient protein is often observed, raising uncertainty regarding frequency its administration. Additionally, various RNA therapeutics may necessitate repeated dosing to achieve optimal therapeutic outcomes. Nevertheless, impact administrations mRNA/LNP on immune responses efficacy remains unclear. In this study, we investigated influence formulation parameters, specifically ionizable lipids polyethylene glycol (PEG) lipids, repeat administration mRNA/LNP. Our findings revealed that had no discernible dose-responsive administrations, whereas structure molar ratio PEG were primary factors affected performance. optimization LNP with confirmed sustained after administrations. This study highlights critical importance optimizing formulations requiring

Language: Английский

In Situ Reprogramming of Immune Cells Using Synthetic Nanomaterials DOI

Shihong Nie,

Yuyang Qin,

Liyuan Ou

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(15)

Published: Jan. 17, 2024

In the past decade, adoptive cell therapy with chimeric antigen receptor-T (CAR-T) cells has revolutionized cancer treatment. However, complexity and high costs involved in manufacturing current greatly inhibit its widespread availability access. To address this, situ therapy, which directly reprograms immune inside body, recently been developed as a promising alternative. Here, an overview of recent progress development synthetic nanomaterials is provided to deliver plasmid DNA or mRNA for reprogramming T macrophages, focusing especially on CAR therapies. Also, main challenges are discussed some approaches overcome these barriers fulfill clinical applications proposed.

Language: Английский

Citations

9

Lipid-Based Nanoformulations for Drug Delivery: An Ongoing Perspective DOI Creative Commons
Mubashar Rehman, Nayab Tahir, Muhammad Sohail

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(11), P. 1376 - 1376

Published: Oct. 26, 2024

Oils and lipids help make water-insoluble drugs soluble by dispersing them in an aqueous medium with the of a surfactant enabling their absorption across gut barrier. The emergence microemulsions (thermodynamically stable), nanoemulsions (kinetically self-emulsifying drug delivery systems added unique characteristics that suitable for prolonged storage controlled release. In 1990s, solid-phase were introduced to reduce leakage from nanoparticles prolong Manipulating structure emulsions solid lipid has enabled multifunctional loading therapeutic macromolecules such as proteins, nucleic acid, vaccines, etc. Phospholipids surfactants well-defined polar head carbon chain have been used prepare bilayer vesicles known liposomes niosomes, respectively. increasing knowledge targeting ligands external factors gain control over pharmacokinetics ever-increasing number synthetic are expected vesicular preferred choice encapsulation targeted agents. This review discusses different oil-based nanoparticulate drugs. salient features each system highlighted, special emphasis is given studies compare them.

Language: Английский

Citations

9

Cancer nanomedicine: Smart arsenal in the war against cancer DOI
Muneeb Ullah, Uzma Azeem Awan, Abdul Muhaymin

et al.

Inorganic Chemistry Communications, Journal Year: 2025, Volume and Issue: unknown, P. 114030 - 114030

Published: Feb. 1, 2025

Language: Английский

Citations

1

mRNA vaccine platforms: linking infectious disease prevention and cancer immunotherapy DOI Creative Commons
Dariush Haghmorad, Majid Eslami,

Niloufar Orooji

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: March 12, 2025

The advent of mRNA vaccines, accelerated by the global response to COVID-19 pandemic, marks a transformative shift in vaccine technology. In this article, we discuss development, current applications, and prospects vaccines for both prevention treatment infectious diseases oncology. By leveraging capacity encode antigens within host cells directly, provide versatile scalable platform suitable addressing broad spectrum pathogens tumor-specific antigens. We highlight recent advancements design, innovative delivery mechanisms, ongoing clinical trials, with particular emphasis on their efficacy combating diseases, such as COVID-19, Zika, influenza, well emerging potential cancer immunotherapy. also address critical challenges, including stability, optimization immune responses, broader issue accessibility. Finally, review strategies advancing next-generation aim overcoming limitations technology enhancing preventive therapeutic approaches oncological diseases.

Language: Английский

Citations

1

Recent advances in the development of sialyltransferase inhibitors to control cancer metastasis: A comprehensive review DOI Open Access

Ranim Al Saoud,

Amar Hamrouni, Adi Idris

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 165, P. 115091 - 115091

Published: July 6, 2023

Metastasis accounts for the majority of cancer-associated mortalities, representing a huge health and economic burden. One mechanisms that enables metastasis is hypersialylation, characterized by an overabundance sialylated glycans on tumor surface, which leads to repulsion detachment cells from original tumor. Once are mobilized, hijack natural killer T-cells through self-molecular mimicry activatea downstream cascade molecular events result in inhibition cytotoxicity inflammatory responses against cancer cells, ultimately leading immune evasion. Sialylation mediated family enzymes known as sialyltransferases (STs), catalyse transfer sialic acid residue donor, CMP-sialic acid, onto terminal end acceptor such N-acetylgalactosamine cell-surface. Upregulation STs increases hypersialylation up 60% considered distinctive hallmark several types cancers pancreatic, breast, ovarian cancer. Therefore, inhibiting has emerged potential strategy prevent metastasis. In this comprehensive review, we discuss recent advances designing novel sialyltransferase inhibitors using ligand-based drug design high-throughput screening synthetic entities, emphasizing most successful approaches. We analyse limitations challenges selective, potent, cell-permeable ST hindered further development into clinical trials. conclude analysing emerging opportunities, including advanced delivery methods increase these enrich clinics with therapeutics combat

Language: Английский

Citations

22

Biomaterials-mediated CRISPR/Cas9 delivery: recent challenges and opportunities in gene therapy DOI Creative Commons
Ankit Kumar Dubey, Ebrahim Mostafavi

Frontiers in Chemistry, Journal Year: 2023, Volume and Issue: 11

Published: Sept. 28, 2023

The use of biomaterials in delivering CRISPR/Cas9 for gene therapy infectious diseases holds tremendous potential. This innovative approach combines the advantages with protective properties biomaterials, enabling accurate and efficient editing while enhancing safety. Biomaterials play a vital role shielding components, such as lipid nanoparticles or viral vectors, from immunological processes degradation, extending their effectiveness. By utilizing flexibility tailored systems can be designed to address specific genetic diseases, paving way personalized therapeutics. Furthermore, this delivery method offers promising avenues combating illnesses by precisely modifying pathogen genomes, reducing pathogenicity. facilitate site-specific modifications, ensuring effective infected cells minimizing off-target effects. However, challenges remain, including optimizing efficiency, effects, long-term safety, establishing scalable production techniques. Thorough research, pre-clinical investigations, rigorous safety evaluations are imperative successful translation laboratory clinical applications. In review, we discussed how using revolutionizes disease treatment, offering precise safe capabilities potential significantly improve human health quality life.

Language: Английский

Citations

21

Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications DOI Creative Commons
Yingying Shi,

Miaoyuan Shi,

Yì Wáng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 14, 2024

Abstract In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge can be largely attributed to demonstration of distinct advantages offered by various mRNA molecules, alongside rapid advancements nucleic delivery systems. It is noteworthy that immunogenicity presents a double-edged sword. context immunotherapy, extra supplementation adjuvant generally required for induction robust immune responses. Conversely, non-immunotherapeutic scenarios, activation unwanted considering host tolerability high expression demand mRNA-encoded functional proteins. Herein, mainly focused on linear non-replicating mRNA, we overview preclinical clinical progress prospects medicines encompassing vaccines other therapeutics. We also highlight importance focusing host-specific variations, including age, gender, pathological condition, concurrent medication individual patient, maximized efficacy safety upon administration. Furthermore, deliberate potential challenges may encounter realm disease treatment, current endeavors improvement, as well application future advancements. Overall, this review aims present comprehensive understanding mRNA-based therapies while illuminating prospective development drugs.

Language: Английский

Citations

7

Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders DOI Creative Commons

Porkizhi Arjunan,

Durga Kathirvelu,

Gokulnath Mahalingam

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(7), P. 2885 - 2900

Published: April 22, 2024

Inherited genetic disorders of the liver pose a significant public health burden. Liver transplantation is often limited by availability donor livers and exorbitant costs immunosuppressive therapy. To overcome these limitations, nucleic acid therapy provides hopeful alternative that enables gene repair, supplementation, silencing with suitable vectors. Though viral vectors are most efficient preferred for therapy, pre-existing immunity debilitating immune responses limit their use. As potential alternative, lipid nanoparticle-mediated being explored to deliver multiple forms, including pDNA, mRNA, siRNA, proteins. Herein, we discuss broader applications nanoparticles, from protein replacement restoring disease mechanism through delivery editing, as well preclinical clinical studies transplantation.

Language: Английский

Citations

6

Comprehensive analysis of lipid nanoparticle formulation and preparation for RNA delivery DOI Creative Commons
Md. Anamul Haque, Archana Shrestha, Constantinos M. Mikelis

et al.

International Journal of Pharmaceutics X, Journal Year: 2024, Volume and Issue: 8, P. 100283 - 100283

Published: Sept. 10, 2024

Language: Английский

Citations

6

Advancing CAR-based immunotherapies in solid tumors: CAR- macrophages and neutrophils DOI Creative Commons

Yanling Liang,

Qumiao Xu,

Qianqian Gao

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 28, 2023

Macrophages and neutrophils are the main components of innate immune system play important roles in promoting angiogenesis, extracellular matrix remodeling, cancer cell proliferation, metastasis tumor microenvironment (TME). They can also be harnessed to mediate cytotoxic killing effects orchestrate effective anti-tumor responses with proper stimulation modification. Therefore, macrophages have strong potential immunotherapy. In this review, we briefly outlined applications or adoptive therapies, focused on chimeric antigen receptor (CAR)-engineered (CAR-Ms) (CAR-Ns). We summarized construction strategies, preclinical clinical studies CAR-Ms CAR-Ns. end, discussed limitations challenges CAR-Ns, as well future research directions extend their treating solid tumors.

Language: Английский

Citations

15