Application of engineered extracellular vesicles for targeted tumor therapy

Zhang, Fusheng; Guo, JJ; Zhang, Zhenghou; Duan, Meiqi; Wang, Guang; Qian, Yi-Ping; Zhao, Haiying; Yang, Zhi; Jiang, Xiaofeng

doi:10.1186/s12929-022-00798-y

Cited by 42 publications

(44 citation statements)

References 217 publications

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“…Potential applications of exosomes as antitumor drug carriers are comprehensively discussed in a previous study by our group, which show utility as specific drug carriers for tumor-targeted therapy owing to low immunogenicity and biocompatibility [ 14 , 305 ]. However, specific conditions of TME (such as hypoxia or metabolism) may affect the morphology or heterogeneity of exosomes and Tu-Exo may exert tumorigenic effects [ 306 ].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

et al. 2022

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The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, and immunosuppression. One of the most common RNA modifications, N6-methyladenosine (m6A) methylation, is widely involved in the regulation of physiological and pathological processes, including tumor development. Compelling evidence indicates that m6A methylation regulates transcription and protein expression through shearing, export, translation, and processing, thereby participating in the dynamic evolution of TME. Specifically, m6A methylation-mediated adaptation to hypoxia, metabolic dysregulation, and phenotypic shift of immune cells synergistically promote the formation of an immunosuppressive TME that supports tumor proliferation and metastasis. In this review, we have focused on the involvement of m6A methylation in the dynamic evolution of tumor-adaptive TME and described the detailed mechanisms linking m6A methylation to change in tumor cell biological functions. In view of the collective data, we advocate treating TME as a complete ecosystem in which components crosstalk with each other to synergistically achieve tumor adaptive changes. Finally, we describe the potential utility of m6A methylation-targeted therapies and tumor immunotherapy in clinical applications and the challenges faced, with the aim of advancing m6A methylation research.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

et al. 2022

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“…Furthermore, drug delivery using the substance-transport capacity of EVs can be broadly divided into two types. One is the pre-loading method, which modifies EVproducing cells, and the other is the post-loading method, in which the recovered EVs are chemically or physically loaded with a drug [145][146][147][148][149]. In the post-loading method, at first, the electroporation method is used to introduce a substance using an electric current [126].…”

Section: Preparation Of Evs As Ddssmentioning

confidence: 99%

Extracellular Vesicles as Novel Drug-Delivery Systems through Intracellular Communications

Matsuzaka

Yashiro

2022

Membranes

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Since it has been reported that extracellular vesicles (EVs) carry cargo using cell-to-cell comminication according to various in vivo situations, they are exprected to be applied as new drug-delivery systems (DDSs). In addition, non-coding RNAs, such as microRNAs (miRNAs), have attracted much attention as potential biomarkers in the encapsulated extracellular-vesicle (EV) form. EVs are bilayer-based lipids with heterogeneous populations of varying sizes and compositions. The EV-mediated transport of contents, which includes proteins, lipids, and nucleic acids, has attracted attention as a DDS through intracellular communication. Many reports have been made on the development of methods for introducing molecules into EVs and efficient methods for introducing them into target vesicles. In this review, we outline the possible molecular mechanisms by which miRNAs in exosomes participate in the post-transcriptional regulation of signaling pathways via cell–cell communication as novel DDSs, especially small EVs.

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“…As newly emerging regenerative tools, biomaterials could potentially provide a platform for enhancing their bioavailability, sustaining the release of EVs, and maximizing the effect of chemotherapeutic drugs. 231 The recent approach of packaging EVs within biomaterial systems is advantageous for delivering and retaining EVs to the target site. Contemporary techniques indicate that the biomaterial-loaded EVs are a much more promising tool for drug delivery, modification of TME, and alteration of chemoresistance properties of CSCs.…”

Section: Evs' Role In Engineering 3d Cancer Stem Cell Models Using Bi...mentioning

confidence: 99%

Bench to Bedside: New Therapeutic Approaches with Extracellular Vesicles and Engineered Biomaterials for Targeting Therapeutic Resistance of Cancer Stem Cells

Ingavle

Das

2022

ACS Biomater. Sci. Eng.

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Cancer has recently been the second leading cause of death worldwide, trailing only cardiovascular disease. Cancer stem cells (CSCs), represented as tumor-initiating cells (TICs), are mainly liable for chemoresistance and disease relapse due to their self-renewal capability and differentiating capacity into different types of tumor cells. The intricate molecular mechanism is necessary to elucidate CSC's chemoresistance properties and cancer recurrence. Establishing efficient strategies for CSC maintenance and enrichment is essential to elucidate the mechanisms and properties of CSCs and CSC-related therapeutic measures. Current approaches are insufficient to mimic the in vivo chemical and physical conditions for the maintenance and growth of CSC and yield unreliable research results. Biomaterials are now widely used for simulating the bone marrow microenvironment. Biomaterialbased three-dimensional (3D) approaches for the enrichment of CSC provide an excellent promise for future drug discovery and elucidation of molecular mechanisms. In the future, the biomaterial-based model will contribute to a more operative and predictive CSC model for cancer therapy. Design strategies for materials, physicochemical cues, and morphology will offer a new direction for future modification and new methods for studying the CSC microenvironment and its chemoresistance property. This review highlights the critical roles of the microenvironmental cues that regulate CSC function and endow them with drug resistance properties. This review also explores the latest advancement and challenges in biomaterial-based scaffold structure for therapeutic approaches against CSC chemoresistance. Since the recent entry of extracellular vesicles (EVs), cell-derived nanostructures, have opened new avenues of investigation into this field, which, together with other more conventionally studied signaling pathways, play an important role in cell-to-cell communication. Thus, this review further explores the subject of EVs in-depth. This review also discusses possible future biomaterial and biomaterial-EV-based models that could be used to study the tumor microenvironment (TME) and will provide possible therapeutic approaches. Finally, this review concludes with potential perspectives and conclusions in this area.

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Application of engineered extracellular vesicles for targeted tumor therapy

Cited by 42 publications

References 217 publications

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

Extracellular Vesicles as Novel Drug-Delivery Systems through Intracellular Communications

Bench to Bedside: New Therapeutic Approaches with Extracellular Vesicles and Engineered Biomaterials for Targeting Therapeutic Resistance of Cancer Stem Cells

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