AAPS PharmSciTech, Год журнала: 2024, Номер 25(5)
Опубликована: Июнь 7, 2024
Язык: Английский
Advanced Materials, Год журнала: 2023, Номер 35(51)
Опубликована: Май 17, 2023
Abstract Messenger RNA (mRNA) has received great attention in the prevention and treatment of various diseases due to success coronavirus disease 2019 (COVID‐19) mRNA vaccines (Comirnaty Spikevax). To meet therapeutic purpose, it is required that must enter target cells express sufficient proteins. Therefore, development effective delivery systems necessary crucial. Lipid nanoparticle (LNP) represents a remarkable vehicle indeed accelerated applications humans, as several mRNA‐based therapies have already been approved or are clinical trials. In this review, focus on mRNA‐LNP‐mediated anticancer therapy. It summarizes main strategies mRNA‐LNP formulations, discusses representative approaches cancer, points out current challenges possible future directions research field. hoped these delivered messages can help further improve application technology cancer
Язык: Английский
Процитировано
195
Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)
Опубликована: Авг. 17, 2023
Abstract Gene therapy holds great promise for treating a multitude of inherited and acquired diseases by delivering functional genes, comprising DNA or RNA, into targeted cells tissues to elicit manipulation gene expression. However, the clinical implementation remains substantially impeded lack safe efficient delivery vehicles. This review comprehensively outlines novel fastest-growing non-viral vectors, which include liposomes lipid nanoparticles (LNPs), highly branched poly(β-amino ester) (HPAE), single-chain cyclic polymer (SCKP), poly(amidoamine) (PAMAM) dendrimers, polyethyleneimine (PEI). Particularly, we discuss research progress, potential development directions, remaining challenges. Additionally, provide comprehensive overview currently approved therapeutics, as well ongoing trials. With advances in biomedicine, molecular biology, materials science, vectors play an ever-expanding noteworthy role therapy.
Язык: Английский
Процитировано
113
Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)
Опубликована: Сен. 11, 2023
Abstract CircRNAs are a class of single-stranded RNAs with covalently linked head-to-tail topology. In the decades since its initial discovery, their biogenesis, regulation, and function have rapidly disclosed, permitting better understanding adoption them as new tools for medical applications. With development biotechnology molecular medicine, artificial circRNAs been engineered novel vaccines disease treatment prevention. Unlike linear mRNA vaccine which applications were limited by instability, inefficiency, innate immunogenicity, circRNA incorporate internal ribosome entry sites (IRESs) open reading frame (ORF) provides an improved approach to RNA-based vaccination safety, stability, simplicity manufacture, scalability. However, at early stage, optimization, delivery require further evaluation. this review, we comprehensively describe vaccine, including history superiority. We also summarize discuss current methodological research preparation, design, synthesis, purification. Finally, highlight options potential in diseases Considering unique high low protein/peptide-coding capacity special closed-loop construction, circRNA-based therapeutic platforms may superior application prospects broad range diseases.
Язык: Английский
Процитировано
106
Advanced Materials, Год журнала: 2023, Номер 36(6)
Опубликована: Сен. 19, 2023
Abstract Insufficient activation of the stimulator interferon genes (STING) signaling pathway and profoundly immunosuppressive microenvironment largely limits effect cancer immunotherapy. Herein, tumor (TME)‐responsive nanoparticles (PMM NPs) are exploited that simultaneously harness STING Toll‐like receptor 4 (TLR4) to augment via TLR4‐mediated nuclear factor‐kappa B stimulation, leading increased secretion type I interferons (i.e., 4.0‐fold enhancement IFN‐β) pro‐inflammatory cytokines promote a specific T cell immune response. Moreover, PMM NPs relieve immunosuppression TME by decreasing percentage regulatory cells, polarizing M2 macrophages M1 type, thus creating an immune‐supportive unleash cascade adaptive Combined with anti‐PD‐1 antibody, synergistic efficacy is achieved in both inflamed colorectal noninflamed metastatic breast models. rechallenging tumor‐free animals homotypic cells induced complete rejection, indicating generation systemic antitumor memory. These TME‐responsive may open new avenue achieve spatiotemporal orchestration activation, providing promising clinical candidate for next‐generation
Язык: Английский
Процитировано
67
Vaccines, Год журнала: 2024, Номер 12(2), С. 186 - 186
Опубликована: Фев. 12, 2024
In recent years, lipid nanoparticles (LNPs) have attracted extensive attention in tumor immunotherapy. Targeting immune cells cancer therapy has become a strategy of great research interest. mRNA vaccines are potential choice for immunotherapy, due to their ability directly encode antigen proteins and stimulate strong response. However, the mode delivery lack stability key issues limiting its application. LNPs an excellent carrier, structural biocompatibility make them effective means delivering specific targets. This study summarizes progress LNP carrier-assisted targeted controlled release immunity. The role improving stability, immunogenicity, targeting is discussed. review aims systematically summarize latest immunity provide new ideas strategies as well more treatment plans patients.
Язык: Английский
Процитировано
58
Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(11)
Опубликована: Март 4, 2024
Nanoparticle-based RNA delivery has shown great progress in recent years with the approval of two mRNA vaccines for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and a liver-targeted siRNA therapy. Here, we discuss preclinical clinical advancement new generations therapies along multiple axes. Improvements cargo design such as circularization data-driven untranslated region optimization can drive better expression. New materials discovery research driven improved to extrahepatic targets lung splenic immune cells, which could lead pulmonary gene therapy cancer vaccines, respectively. Other organs even specific cell types be targeted via conjugation small molecule ligands, antibodies, or peptides nanoparticles. Moreover, response any nanoparticle plays crucial role determining efficacy. Targeting increased immunogenicity without induction reactogenic side effects is while minimization important therapies. developments have addressed each these priorities. Last, range trials targeting diverse organs, types, diseases suggest some key advances that may play next wave
Язык: Английский
Процитировано
38
Biotechnology Advances, Год журнала: 2025, Номер 81, С. 108546 - 108546
Опубликована: Фев. 26, 2025
Язык: Английский
Процитировано
3
MedComm, Год журнала: 2023, Номер 4(4)
Опубликована: Авг. 1, 2023
Abstract Immune checkpoint inhibitors (ICIs) have shown remarkable success in cancer treatment. However, patients without sufficient antitumor immunity, numerous data indicate that blocking the negative signals elicited by immune checkpoints is ineffective. Drugs stimulate activation‐related pathways are emerging as another route for improving immunotherapy. In addition, development of nanotechnology presents a promising platform tissue and cell type‐specific delivery improved uptake immunomodulatory agents, ultimately leading to enhanced immunotherapy reduced side effects. this review, we summarize discuss latest developments nanoparticles (NPs) immuno‐oncology therapy with focus on lipid‐based NPs (lipid‐NPs), including characteristics advantages various types. Using agonists targeting stimulation interferon genes (STING) transmembrane protein an exemplar, review potential lipid‐NPs augment STING agonist therapy. Furthermore, present recent findings underlying mechanisms how pathway activation fosters immunity regulates tumor microenvironment provide summary distinct preclinical studies clinical trials. Ultimately, conduct critical assessment obstacles future directions utilization enhance
Язык: Английский
Процитировано
34
mBio, Год журнала: 2023, Номер 15(1)
Опубликована: Дек. 11, 2023
messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, the inherent instability of mRNA nonspecificity lipid nanoparticle-encapsulated (LNP) delivery systems result need for cold storage relatively short-duration immune response to vaccines. Herein, we develop novel vaccine form circRNAs encapsulated LNPs, circular structure enhances their stability. Lyophilization is considered most effective method long-term preservation this process may irreversible damage nanoparticles, particularly potential disruption targeting modifications on LNPs. During selection lymph node-targeting ligands, found that LNPs modified with mannose maintained physical properties almost unchanged after lyophilization. Additionally, specificity immunogenicity remained unaffected. In contrast, even addition cryoprotectants such as sucrose, were impaired, leading an obvious decrease immunogenicity. This be attributed protective role surface during Freshly prepared lyophilized mLNP-circRNA elicited comparable responses both rabies virus model SARS-CoV-2 model. Our data demonstrated elicit robust while improving stability lyophilization, no compromise tissue specificity. Therefore, mannose-modified LNP-circRNA represent promising design strategy.
Язык: Английский
Процитировано
32
Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(10)
Опубликована: Янв. 10, 2024
Dendritic cell (DC) maturation and antigen presentation are key factors for successful vaccine-based cancer immunotherapy. This study developed manganese-based layered double hydroxide (Mn-LDH) nanoparticles as a self-adjuvanted vaccine carrier that not only promoted DC through synergistically depleting endogenous glutathione (GSH) activating STING signaling pathway, but also facilitated the delivery of model ovalbumin (OVA) into lymph nodes subsequent in DCs. Significant therapeutic-prophylactic efficacy OVA-loaded Mn-LDH (OVA/Mn-LDH) nanovaccine was determined by tumor growth inhibition mice bearing B16-OVA tumor. Our results showed OVA/Mn-LDH could be potent system development without need adjuvant. Therefore, combination GSH exhaustion pathway activation might an advisable approach promoting presentation, finally improving efficacy.
Язык: Английский
Процитировано
15