Novel co‐delivery of oridonin and docetaxel nanoliposome for an enhanced antitumor effect on esophageal cancer DOI Open Access
Xi Chen,

Hengyu Mao,

Feng Peng

et al.

The Journal of Gene Medicine, Journal Year: 2024, Volume and Issue: 26(8)

Published: Aug. 1, 2024

Abstract Introduction Esophageal cancer is one of the major cancers in China. Most patients with esophageal are diagnosed at an advanced stage, and 5 year survival rate discouraging. Combined chemotherapy a common method for treatment cancer. Methods In this study, distearoyl phosphatidyl ethanolamine polyethylene glycol 2000 (DSPE‐PEG2000) nanoliposomes (NLPs) encapsulating anticancer drugs docetaxel (DOX) oridonin (ORD) were prepared, their ability to enhance release was determined. The NLP system characterized by transmission electron microscopy, particle size encapsulation efficiency. addition, characteristics pharmacodynamics these also studied detail. Results When DOX/ORD ratio 2:1, higher proportion DOX led stronger synergy effect. NLPs prepared high‐pressure homogenization had uniform spherical morphology. mean polydispersity index determined be 246.4 0.163, respectively. stability results showed that no significant change observed size, zeta potential, Encapsulation efficiency dynamic light scattering during observation period. vitro illustrated acidic environment tumor might beneficial drug release. three‐dimensional tumorsphere can reach interior spheres, which destroys structure cells, resulting irregular spheres. vivo study indicated obvious targeting effect on subcutaneous tumors have potential actively deliver tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining used detect apoptosis. could significantly induce apoptosis inhibit growth. Conclusion anti‐tumor activity, expected promising co‐delivery platform

Language: Английский

Lipid Nanoparticle-Associated Inflammation is Triggered by Sensing of Endosomal Damage: Engineering Endosomal Escape Without Side Effects DOI Open Access
Serena Omo‐Lamai, Yufei Wang, Manthan N. Patel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 18, 2024

Abstract Lipid nanoparticles (LNPs) have emerged as the dominant platform for RNA delivery, based on their success in COVID-19 vaccines and late-stage clinical studies other indications. However, we others shown that LNPs induce severe inflammation, massively aggravate pre-existing inflammation. Here, using structure-function screening of lipids analyses signaling pathways, elucidate mechanisms LNP-associated inflammation demonstrate solutions. We show LNPs’ hallmark feature, endosomal escape, which is necessary expression, also directly triggers by causing membrane damage. Large, irreparable, holes are recognized cytosolic proteins called galectins, bind to sugars inner then regulate downstream find inhibition galectins abrogates both vitro vivo . rapidly biodegradable ionizable can preferentially create smaller size reparable sorting complex required transport (ESCRT) pathway. Ionizable producing such ESCRT-recruiting produce high expression from cargo mRNA with minimal Finally, routes non-inflammatory LNPs, either galectin or lipids, compatible therapeutic mRNAs ameliorate disease models. without lead exacerbation these In summary, escape induces damage be controlled inhibiting (large hole detectors) ESCRT These strategies should generally safer used treat inflammatory diseases.

Language: Английский

Citations

17

Writers, readers, and erasers RNA modifications and drug resistance in cancer DOI Creative Commons
Di Chen, Xinyu Gu,

Yeltai Nurzat

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

Citations

16

Ionizable Lipids with Optimized Linkers Enable Lung-Specific, Lipid Nanoparticle-Mediated mRNA Delivery for Treatment of Metastatic Lung Tumors DOI Creative Commons
Gonna Somu Naidu, Riccardo Rampado, Preeti Sharma

et al.

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

Published: Feb. 6, 2025

Lipid nanoparticles (LNPs) have emerged as a groundbreaking delivery system for vaccines and therapeutic mRNAs. Ionizable lipids are the most pivotal component of LNPs due to their ability electrostatically interact with mRNA, allowing its encapsulation while concurrently enabling endosomal escape following cellular internalization. Thus, extensive research has been performed optimize ionizable lipid structure develop formulations that well tolerated allow efficient targeting different organs result in high sustained mRNA expression. However, one facet lipids' mostly overlooked: linker segment between headgroup tails. Here, we screened rationally designed library biodegradable linkers. We extensively characterized formulated using these elucidated how minor structural changes radically influenced LNPs' biodistribution vivo. showed use amide urea linkers can modulate pKa, resulting an improved specificity lung transfection. Finally, demonstrated (lipid 35) form entrapping bacterial toxin [pseudomonas exotoxin A (mmPE)] reduced tumor burden significantly increased survival mice metastasis.

Language: Английский

Citations

3

Delivery of nucleic acid based genome editing platforms via lipid nanoparticles: Clinical applications DOI

Razan Masarwy,

Lior Stotsky‐Oterin,

Aviad Elisha

et al.

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 211, P. 115359 - 115359

Published: June 12, 2024

Language: Английский

Citations

15

mRNA vaccines for infectious diseases — advances, challenges and opportunities DOI
Norbert Pardi, Florian Krammer

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Language: Английский

Citations

14

Lipid nanoparticle (LNP) mediated mRNA delivery in cardiovascular diseases: Advances in genome editing and CAR T cell therapy DOI

Setareh Soroudi,

Mahmoud Reza Jaafari,

Leila Arabi

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 372, P. 113 - 140

Published: June 15, 2024

Language: Английский

Citations

10

The dynamic process of mRNA delivery by lipid nanoparticles in vivo DOI

Runpu Ma,

Yuting Li, Yi Wei

et al.

Nano Today, Journal Year: 2024, Volume and Issue: 57, P. 102325 - 102325

Published: May 30, 2024

Language: Английский

Citations

9

Controlled preparation of lipid nanoparticles in microreactors: Mixing time, morphology and mRNA delivery DOI

D.Q. Chen,

Zhikai Liu,

Letao Guo

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: 505, P. 159318 - 159318

Published: Jan. 6, 2025

Language: Английский

Citations

1

Enhanced stability and efficacy of a lyophilized mRNA SARS-CoV-2 vaccine incorporating novel Ionizable lipids after one year storage at 25ºC DOI Creative Commons

Elena Mata,

Esther Broset, Carlos Matute

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract mRNA vaccines have shown great efficacy against SARS-CoV-2, yet challenges remain in optimizing vaccine components to achieve enhanced immune response and stability. In this study, we developed CPVax-CoV, a new lyophilized that features novel thiolactone-based ionizable lipids newly designed untranslated regions (UTRs) for expression. Incorporation of these optimized into our candidate CPVax-CoV significantly improved responses mice compared commercially available vaccines. Moreover, has proven be thermostable, maintaining its biological activity up one year at 4°C 25°C after lyophilization, overcoming the cold-chain limitations current This demonstrates protective ancestral SARS-CoV-2 Omicron XBB variant, offering scalable solution global distribution pandemic preparedness. These findings underscore potential platform future next-generation development.

Language: Английский

Citations

1

Revolutionizing Dentistry: Preclinical Insights and Future Applications of mRNA Vaccines in Dentistry—A Narrative Review DOI Creative Commons
Luciana Koren,

Andro Koren,

Robert Likić

et al.

Dentistry Journal, Journal Year: 2025, Volume and Issue: 13(2), P. 79 - 79

Published: Feb. 13, 2025

Background: Recent advances in mRNA vaccine technology, accelerated by the global COVID-19 pandemic, have generated significant interest their applications beyond infectious diseases. Dentistry has emerged as a promising field for exploring potential of mRNA-based therapies preventing and treating oral Objectives: This narrative review aims to evaluate current status development its preclinical health, focusing on periodontal disease, dental caries, regenerative medicine, implantology, cancer. Methods: The synthesizes findings from studies, including research conducted animal models vitro, assess modulate immune responses promote tissue regeneration cavity. Clinical trials were only mentioned context broader areas implementation such oncology immunotherapy. Results: studies highlight capacity vaccines enhance body's response facilitate repair processes. Despite these results, challenges persist delivering effectively within complex environment. These include stability, delivery mechanisms, modulation responses. Conclusions: While offer promise revolutionizing health care, they face notable limitations concerning safety, efficacy, clinical feasibility. Overcoming obstacles through further is essential unlock full translational ensure safe effective integration into practice.

Language: Английский

Citations

1