Ultrasound Responsive Nanovaccine Armed with Engineered Cancer Cell Membrane and RNA to Prevent Foreseeable Metastasis

Sun, Wenqi; Ji, Panpan; Zhou, Tian; Li, Zhelong; Xing, Changyang; Zhang, Liang; Wei, Mengying; Yang, Guodong; Yuan, Lijun

doi:10.1002/advs.202301107

Cited by 14 publications

(8 citation statements)

References 59 publications

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“…Therefore, cationic chemical groups are required to construct an RNA delivery system. , To encapsulate siRNA with high efficiency and effectively downregulate targeted genes, were synthesized using the double solvent evaporation technique. , Moreover, a cancer vaccine based on PLGA, and engineered tumor cell membrane coating was designed to encapsulate mRNA and the sonosensitizer chlorin e6 (Ce6). The nanosized vaccine exhibited high efficiency in delivering antigen presentation cells (APCs) after subcutaneous injection, enhancing mRNA escape from the endosome, and promoting antigen presentation . Overall, these findings demonstrate the potential of PLGA-based RNA delivery systems in various applications, including gene therapy and cancer treatment.…”

Section: Chemical Modifications On Rna Nanodelivery Platformsmentioning

confidence: 68%

“…The nanosized vaccine exhibited high efficiency in delivering antigen presentation cells (APCs) after subcutaneous injection, enhancing mRNA escape from the endosome, and promoting antigen presentation. 485 Overall, these findings demonstrate the potential of PLGA-based RNA delivery systems in various applications, including gene therapy and cancer treatment.…”

Section: Diverse Polymer Selection Based On Therapeuticmentioning

confidence: 70%

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Chemically Modified Platforms for Better RNA Therapeutics

Shi,

Zhen,

Zhang

et al. 2024

Chem. Rev.

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RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential in disease prevention and treatment. However, despite their remarkable achievements, these therapies encounter substantial challenges including low stability, susceptibility to degradation by nucleases, and a prominent negative charge, thereby hindering further development. Chemically modified platforms have emerged as a strategic innovation, focusing on precise alterations either on the RNA moieties or their associated delivery vectors. This comprehensive review delves into these platforms, underscoring their significance in augmenting the performance and translational prospects of RNA-based therapeutics. It encompasses an in-depth analysis of various chemically modified delivery platforms that have been instrumental in propelling RNA therapeutics toward clinical utility. Moreover, the review scrutinizes the rationale behind diverse chemical modification techniques aiming at optimizing the therapeutic efficacy of RNA molecules, thereby facilitating robust disease management. Recent empirical studies corroborating the efficacy enhancement of RNA therapeutics through chemical modifications are highlighted. Conclusively, we offer profound insights into the transformative impact of chemical modifications on RNA drugs and delineates prospective trajectories for their future development and clinical integration. CONTENTS1. Introduction 930 2. Current Status and Challenges of RNA Therapeutics in Clinics 933 2.1. Molecular Mechanisms and Clinical Research Progress of RNAs 934 2.1.1. ASO 934 2.1.2. siRNA 934 2.1.3. Aptamer 936 2.1.4. mRNA 936 2.1.5. RNA Therapeutics on the Cusp of Clinical Breakthroughs 938 2.2. Major Challenges of Current RNA Therapeutics in Clinics 940 2.

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Section: Chemical Modifications On Rna Nanodelivery Platformsmentioning

confidence: 68%

Section: Diverse Polymer Selection Based On Therapeuticmentioning

confidence: 70%

Chemically Modified Platforms for Better RNA Therapeutics

Shi,

Zhen,

Zhang

et al. 2024

Chem. Rev.

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“…In the xenotransplantation mouse models of RM 1 (prostate cancer), MC38 (colon cancer) and B16 (melanoma), ultrasound-mediated cavitation induces tumor cell necrosis, which significantly increases the damage related to molecular mode damping release and tumor antigen presentation, thus making the tumor sensitive to ICB treatment ( Hu et al, 2022 ). Sun W’s experiments on 4T1 homologous mouse model proved that ultrasound sensitizer CE 6 and ultrasound irradiation jointly promoted mRNA escape from endosome, thus enhancing antigen presentation, effectively triggering anti-tumor immunity and preventing tumor metastasis ( Sun et al, 2023 ). In addition, a nano-scale cancer vaccine was designed in this study, which was sealed by Ce6 and other materials based on PLGA (lactic co glycolic acid).…”

Section: Mechanism and Application Of Ultrasound Combined With Microb...mentioning

confidence: 99%

Ultrasound combined with microbubble mediated immunotherapy for tumor microenvironment

Wu,

Li,

Shu

et al. 2024

Front. Pharmacol.

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The tumor microenvironment (TME) plays an important role in dynamically regulating the progress of cancer and influencing the therapeutic results. Targeting the tumor microenvironment is a promising cancer treatment method in recent years. The importance of tumor immune microenvironment regulation by ultrasound combined with microbubbles is now widely recognized. Ultrasound and microbubbles work together to induce antigen release of tumor cell through mechanical or thermal effects, promoting antigen presentation and T cells’ recognition and killing of tumor cells, and improve tumor immunosuppression microenvironment, which will be a breakthrough in improving traditional treatment problems such as immune checkpoint blocking (ICB) and himeric antigen receptor (CAR)-T cell therapy. In order to improve the therapeutic effect and immune regulation of TME targeted tumor therapy, it is necessary to develop and optimize the application system of microbubble ultrasound for organs or diseases. Therefore, the combination of ultrasound and microbubbles in the field of TME will continue to focus on developing more effective strategies to regulate the immunosuppression mechanisms, so as to activate anti-tumor immunity and/or improve the efficacy of immune-targeted drugs, At present, the potential value of ultrasound combined with microbubbles in TME targeted therapy tumor microenvironment targeted therapy has great potential, which has been confirmed in the experimental research and application of breast cancer, colon cancer, pancreatic cancer and prostate cancer, which provides a new alternative idea for clinical tumor treatment. This article reviews the research progress of ultrasound combined with microbubbles in the treatment of tumors and their application in the tumor microenvironment.

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“…228 from engineered tumor cells by disturbed alternative splicing), and Ce6. 229 This cancer vaccine could be efficiently delivered to APCs in lymph nodes after a subcutaneous injection. Subsequently, the cell membrane and RNA in the APCs disturbed splicing, resembling metastatic cells, which provided neoantigens of metastatic cancer in advance.…”

Section: Combination Therapymentioning

confidence: 99%

“…Besides, ultrasound can promote endosomal escape of mRNA to facilitate efficient translation and improve therapeutic efficacy . In one study, Sun et al prepared a PLGA-based cancer vaccine containing tumor cell membrane proteins, mRNA (derived from engineered tumor cells by disturbed alternative splicing), and Ce6 . This cancer vaccine could be efficiently delivered to APCs in lymph nodes after a subcutaneous injection.…”

Section: Strategies To Enhance the Efficacy Of Mrna Cancer Vaccinesmentioning

confidence: 99%

mRNA Cancer Vaccines: Construction and Boosting Strategies

Liu,

Huang,

Yang

et al. 2023

ACS Nano

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In late 2020, the U.S. Food and Drug Administration (FDA) approved a lipid-based mRNA vaccine for the prevention of COVID-19, which has pushed this field to be more closely studied and motivated researchers to delve deeper into mRNA therapeutics. To date, the research on mRNA cancer vaccines has been developed rapidly, and substantial hopeful therapeutic results have been achieved against various solid tumors in clinical trials. In this review, we first introduce three main components of mRNA cancer vaccines, including mRNA antigens, adjuvants, and delivery vectors. Engineering these components can optimize the therapeutic effects of mRNA cancer vaccines. For instance, appropriate modification of mRNA structure can alleviate the poor stability and innate immunogenicity of mRNA, and the use of mRNA delivery vectors can address the issues of low delivery efficiency in vivo. Second, we emphatically discuss some strategies to further improve the efficacy of mRNA cancer vaccines, namely modulating the immunosuppressive tumor environment, optimizing administration routes, achieving targeting delivery to intended tissues or organs, and employing combination therapy. These strategies can strengthen the tumor inhibitory ability of mRNA cancer vaccines and increase the possibility of tumor elimination. Finally, we point out some challenges in the clinical practice of mRNA cancer vaccines and offer our perspectives on future developments in this rapidly evolving field. It is anticipated that mRNA cancer vaccines will be rapidly developed for clinical cancer therapy in the near future.

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Ultrasound Responsive Nanovaccine Armed with Engineered Cancer Cell Membrane and RNA to Prevent Foreseeable Metastasis

Cited by 14 publications

References 59 publications

Chemically Modified Platforms for Better RNA Therapeutics

Chemically Modified Platforms for Better RNA Therapeutics

Ultrasound combined with microbubble mediated immunotherapy for tumor microenvironment

mRNA Cancer Vaccines: Construction and Boosting Strategies

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