Messenger RNA (mRNA) has received great attention in the prevention and treatment of various diseases due to the success of COVID-19 mRNA vaccines (Comirnaty and Spikevax). To meet the therapeutic purpose, it is required that mRNA must enter the target cells and express sufficient proteins. Therefore, the development of effective delivery systems is necessary and crucial. Lipid nanoparticle (LNP) represents a remarkable vehicle that has indeed accelerated mRNA applications in humans, as several mRNA-based therapies have already been approved or are in clinical trials. In this review, we focus on mRNA-LNP mediated anticancer therapy. We summarize the main development strategies of mRNA-LNP formulations, discuss representative therapeutic approaches in cancer, and point out current challenges and possible future directions of this research field. We hope these delivered messages could help further improve the application of mRNA-LNP technology in cancer therapy. This article is protected by copyright. All rights reserved.

Lipid Nanoparticle (LNP) Enables mRNA Delivery for Cancer Therapy.

Abstract Rapid advancements in materials science and nanotechnology, intertwined with oncology, have positioned photothermal therapy (PTT) as a promising noninvasive treatment strategy for cancer. The breast's superficial anatomical location and aesthetic significance render breast cancer a particularly pertinent candidate for the clinical application of PTT following melanoma. This review comprehensively explores the research conducted on the various types of nanoparticles employed in PTT for breast cancer and elaborates on their specific roles and mechanisms of action. The integration of PTT with existing clinical therapies for breast cancer is scrutinized, underscoring its potential for synergistic outcomes. Additionally, the mechanisms underlying PTT and consequential modifications to the tumor microenvironment after treatment are elaborated from a medical perspective. Future research directions are suggested, with an emphasis on the development of integrative platforms that combine multiple therapeutic approaches and the optimization of nanoparticle synthesis for enhanced treatment efficacy. The goal is to push the boundaries of PTT toward a comprehensive, clinically applicable treatment for breast cancer. 

Nanoparticle-based Photothermal Therapy for Breast Cancer Non-Invasive Treatment.

The concept of using mRNA to produce its own medicine in situ in the body makes it an ideal drug candidate, holding great potential to revolutionize the way we approach medicine. The unique characteristics of mRNA, as well as its customizable biomedical functions, call for the rational design of delivery systems to protect and transport mRNA molecules. In this review, a nanoparticle toolkit is presented for the development of mRNA-based therapeutics from a drug delivery perspective. Nano-delivery systems derived from either natural systems or chemical synthesis, in the nature of organic or inorganic materials, are summarised. Delivery strategies in controlling the tissue targeting and mRNA release, as well as the role of nanoparticles in building and boosting the activity of mRNA drugs, will also be introduced. Finally, our insights into the clinical and translational development of mRNA nano-drugs are presented. 

Engineering nanoparticle toolkits for mRNA delivery.

Lipid nanoparticles (LNPs) carrying therapeutic mRNAs hold great promise in treating lung-associated diseases like viral infections, tumors, and genetic disorders. However, because of their thermodynamically unstable nature, traditional LNPs carrying mRNAs need to be stored at low temperatures, which hinders their prevalence. Herein, an efficient lung-specific mRNA delivery platform named five-element nanoparticles (FNPs) is developed in which helper-polymer poly(β-amino esters) (PBAEs) and DOTAP are used in combination. The new strategy endows FNPs with high stability by increasing the charge repulsion between nanoparticles and the binding force of the aliphatic chains within the nanoparticles. The structure-activity relationship (SAR) shows that PBAEs with E1 end-caps, higher degrees of polymerization, and longer alkyl side chains exhibit higher hit rates. Lyophilized FNP formulations can be stably stored at 4 °C for at least 6 months. Overall, a novel delivery platform with high efficiency, specificity, and stability was developed for advancing mRNA-based therapies for lung-associated diseases.

Helper-Polymer Based Five-Element Nanoparticles (FNPs) for Lung-Specific mRNA Delivery with Long-Term Stability after Lyophilization.

RNA-based therapeutics have shown great promise in various medical applications, including cancers, infectious diseases, and metabolic diseases. The recent success of mRNA vaccines for combating the COVID-19 pandemic has highlighted the medical value of RNA drugs. However, one of the major challenges in realizing the full potential of RNA drugs is to deliver RNA into specific organs and tissues in a targeted manner, which is crucial for achieving therapeutic efficacy, reducing side effects, and enhancing overall treatment efficacy. Numerous attempts have been made to pursue targeting, nonetheless, the lack of clear guideline and commonality elucidation has hindered the clinical translation of RNA drugs. In this review, we outline the mechanisms of action for targeted RNA delivery systems and summarize four key factors that influence the targeting delivery of RNA drugs. These factors include the category of vector materials, chemical structures of vectors, administration routes, and physicochemical properties of RNA vectors, and they all notably contribute to specific organ/tissue tropism. Furthermore, we provide an overview of the main RNA-based drugs that are currently in clinical trials, highlighting their design strategies and tissue tropism applications. This review will aid to understand the principles and mechanisms of targeted delivery systems, accelerating the development of future RNA drugs for different diseases.

Targeting materials and strategies for RNA delivery

The lack of organic fluorophores with high quantum yields (QYs) and low liver retention in the second near-infrared (NIR-II) window has become a bottleneck in the bioimaging field. An approach to address these problems is proposed by encapsulating phosphorylated fluorescent dyes into biodegradable calcium phosphate nanoparticles. First, an NIR-II molecule, LJ-2P, is designed with increased water solubility by introducing two phosphate groups. Meanwhile, LJ-2P co-precipitates with calcium ions to form LJ-2P nanoparticles (NPs). The QYs of LJ-2P NPs in aqueous solution is increased by 36.57-fold to 5.12% compared with that of LJ-2P. This unique phenomenon is named as precipitation-enhanced emission (PEE), whose detailed mechanism is explored by femtosecond transient absorption. It is demonstrated that co-precipitation of LJ-2P with calcium ions changes the micro-environment, which restricts the molecular rotation and reduces the interaction of water molecules, especially the excited-state proton transfer. In addition, due to the pH-sensitive nature, more than 80% of the LJ-2P NPs are metabolized in the liver within 24 h. Based on the excellent optical properties and good biocompatibility, high-contrast vascular visualization and breast tumor detecting are achieved. This strategy can apply to other NIR-II fluorophores to achieve high QYs and low liver retention.

A Precipitation-Enhanced Emission (PEE) Strategy for Increasing the Brightness and Reducing the Liver Retention of NIR-II Fluorophores.

Targeted Delivery of mRNA with Polymer-Lipid Nanoparticles for In Vivo Base Editing.

Lung-associated diseases pose a huge threat to human society. Mesenchymal stromal/stem cells (MSCs) hold great promise in the treatment of pulmonary diseases through cell transdifferentiation, paracrine factors, immune regulation, EV secretion, and drug loading. However, intravenous injection of MSCs often resulted in limited lesion tropism and apparent off-target accumulation. The IL-8-CXCR1/2 chemokine axis has been shown to be involved in progression of diseases including lung cancer and acute lung injury (ALI). Herein, we took advantage of this chemokine axis to enhance the homing of MSCs to cancerous and inflammation lesions. The in vivo distribution of MSCs was further monitored real-time by near-infrared region 2 (NIR-II) imaging owing to its outstanding performance in deep tissue imaging. Specifically, a new high-brightness D-A-D NIR-II dye, LJ-858, was synthesized and coprecipitated with a poly(d,l-lactic acid) polymer to form LJ-858 nanoparticles (NPs) with a relative quantum yield of 14.978%. LJ-858 NPs can efficiently label MSCs, and the NIR-II signal can be stable for 14 days without compromising the cell viability. Subcutaneous tracking of labeled MSCs showed no significant decline of NIR-II intensity within 24 h. The enhanced tropism of CXCR2-overexpressing MSCs to A549 tumor cells and the inflamed lung tissue was demonstrated through transwell models. The in vivo and ex vivo NIR-II imaging results further validated the significantly enhanced lesion retention of MSCCXCR2 in the lung cancer and ALI models. Taken together, this work reported a robust strategy to enhance the pulmonary disease tropism by the IL-8-CXCR1/2 chemokine axis. In addition, in vivo distribution of MSCs was successfully visualized by NIR-II imaging, which provides more insights into optimizing protocols for MSC-based therapies in the future.

In Vivo Fate of CXCR2-Overexpressing Mesenchymal Stromal/Stem Cells in Pulmonary Diseases Monitored by Near-Infrared Region 2 Imaging.

Poly(beta-amino ester)-Based Nanoparticles Enable Nonviral Delivery of Base Editors for Targeted Tumor Gene Editing.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Xia He

Author Tools

Chat about Author