Abstract Cancer immunotherapy has revolutionized the approach to cancer treatment of malignant tumors by harnessing the body’s immune system to selectively target cancer cells. Despite remarkable advances, there are still challenges in achieving successful clinical responses. Recent evidence suggests that immune cell-derived exosomes modulate the immune system to generate effective antitumor immune responses, making them a cutting-edge therapeutic strategy. However, natural exosomes are limited in clinical application due to their low drug delivery efficiency and insufficient antitumor capacity. Technological advancements have allowed exosome modifications to magnify their intrinsic functions, load different therapeutic cargoes, and preferentially target tumor sites. These engineered exosomes exert potent antitumor effects and have great potential for cancer immunotherapy. In this review, we describe ingenious modification strategies to attain the desired performance. Moreover, we systematically summarize the tumor-controlling properties of engineered immune cell-derived exosomes in innate and adaptive immunity. Collectively, this review provides a comprehensive and intuitive guide for harnessing the potential of modified immune cell-derived exosome-based approaches, offering valuable strategies to enhance and optimize cancer immunotherapy. 

Modification of immune cell-derived exosomes for enhanced cancer immunotherapy: current advances and therapeutic applications

Ultrasound nanotheranostics: Toward precision medicine.

The responses of patients to tumor therapies vary due to tumor heterogeneity. Tumor stratification has been attracting increasing attention for accurately distinguishing between responders to treatment and non-responders. Nanoprobes with unique physical and chemical properties have great potential for patient stratification. This review begins by describing the features and design principles of nanoprobes that can visualize specific cell types and biomarkers and release inflammatory factors during or before tumor treatment. Then, we focus on the recent advancements in using nanoprobes to stratify various therapeutic modalities, including chemotherapy, radiotherapy (RT), photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), ferroptosis, and immunotherapy. The main challenges and perspectives of nanoprobes in cancer stratification are also discussed to facilitate probe development and clinical applications. 

Nanoprobe-based molecular imaging for tumor stratification.

Microbubbles for human diagnosis and therapy.

As key mediators of cellular communication, extracellular vesicles (EVs) have been actively explored for diagnostic and therapeutic applications. However, effective methods to functionalize EVs and modulate the interaction between EVs and recipient cells are still lacking. Here we report a facile and universal metabolic tagging technology that can install unique chemical tags (e.g., azido groups) onto EVs. The surface chemical tags enable conjugation of molecules via efficient click chemistry, for the tracking and targeted modulation of EVs. In the context of tumor EV vaccines, we show that the conjugation of toll-like receptor 9 agonists onto EVs enables timely activation of dendritic cells and generation of superior antitumor CD8+ T cell response. These lead to 80% tumor-free survival against E.G7 lymphoma and 33% tumor-free survival against B16F10 melanoma. Our study yields a universal technology to generate chemically tagged EVs from parent cells, modulate EV-cell interactions, and develop potent EV vaccines. 

Metabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines

Simple Summary Extracellular vesicles are small membranous particles secreted by cells. Extracellular vesicles facilitate the transportation of biomolecules, such as protein, RNA, and DNA fragments, to communicate with neighboring and distant cells. Cancer cells use extracellular vesicles to hijack the immune system and induce cancer-promoting signals. Modifying extracellular vesicles using surface engineering tools allows the addition of biomolecules for targeted delivery, thus modulating the hijacked tumor immune microenvironment to improve therapeutic efficacy. This review article discusses extracellular vesicle modification strategies explicitly focusing on the approaches used for surface engineering. We revisit the work carried out on the surface-engineered extracellular vesicle and its application in immunomodulating tumor microenvironments for cancer immunotherapy. Abstract Extracellular vesicles (EVs) are lipid bilayer-enclosed bodies secreted by all cell types. EVs carry bioactive materials, such as proteins, lipids, metabolites, and nucleic acids, to communicate and elicit functional alterations and phenotypic changes in the counterpart stromal cells. In cancer, cells secrete EVs to shape a tumor-promoting niche. Tumor-secreted EVs mediate communications with immune cells that determine the fate of anti-tumor therapeutic effectiveness. Surface engineering of EVs has emerged as a promising tool for the modulation of tumor microenvironments for cancer immunotherapy. Modification of EVs’ surface with various molecules, such as antibodies, peptides, and proteins, can enhance their targeting specificity, immunogenicity, biodistribution, and pharmacokinetics. The diverse approaches sought for engineering EV surfaces can be categorized as physical, chemical, and genetic engineering strategies. The choice of method depends on the specific application and desired outcome. Each has its advantages and disadvantages. This review lends a bird’s-eye view of the recent progress in these approaches with respect to their rational implications in the immunomodulation of tumor microenvironments (TME) from pro-tumorigenic to anti-tumorigenic ones. The strategies for modulating TME using targeted EVs, their advantages, current limitations, and future directions are discussed.

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Surface-Engineered Extracellular Vesicles in Cancer Immunotherapy

FN3 linked nanobubbles as a targeted contrast agent for US imaging of cancer-associated human PD-L1.

Extracellular Vesicles — A Versatile Biomaterial In article number 2101387 Rajendran J. C. Bose and co-workers demonstrate an effective anticancer therapy by developing PLGA-nanocarriers loaded with antimiRNA-21 or antimiRNA-10b using engineered tumor cell derived extracellular vesicles (eEVs) that display tumor specific receptor targeting peptide to achieve therapeutic effect by reprogramming cancer cells. 

Engineered Cell‐Derived Vesicles Displaying Targeting Peptide and Functionalized with Nanocarriers for Therapeutic microRNA Delivery to Triple‐Negative Breast Cancer in Mice (Adv. Healthcare Mater. 5/2022)

ADVERTISEMENT RETURN TO ISSUEPREVAdditions and Correc...Additions and CorrectionsNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to “Gold-Nanostar-Chitosan-Mediated Delivery of SARS-CoV-2 DNA Vaccine for Respiratory Mucosal Immunization: Development and Proof-of-Principle”Uday S. KumarUday S. KumarMore by Uday S. Kumarhttps://orcid.org/0000-0002-0354-2353, Rayhaneh AfjeiRayhaneh AfjeiMore by Rayhaneh Afjei, Katherine FerraraKatherine FerraraMore by Katherine Ferrarahttps://orcid.org/0000-0002-4976-9107, Tarik F. Massoud*Tarik F. MassoudMore by Tarik F. Massoudhttps://orcid.org/0000-0002-9694-1408, and Ramasamy Paulmurugan*Ramasamy PaulmuruganMore by Ramasamy Paulmuruganhttps://orcid.org/0000-0001-7155-4738Cite this: ACS Nano 2023, 17, 17, 17596Publication Date (Web):August 15, 2023Publication History Received31 July 2023Published online15 August 2023Published inissue 12 September 2023https://doi.org/10.1021/acsnano.3c07103Copyright © 2023 American Chemical SocietyRequest reuse permissions This publication is free to access through this site. Learn MoreArticle Views254Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-AlertscloseSUBJECTS:Gene delivery,Genetics,Vaccination Get e-Alerts 

Correction to "Gold-Nanostar-Chitosan-Mediated Delivery of SARS-CoV-2 DNA Vaccine for Respiratory Mucosal Immunization: Development and Proof-of-Principle".

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Surface-Engineered Extracellular Vesicles in Cancer Immunotherapy

FN3 linked nanobubbles as a targeted contrast agent for US imaging of cancer-associated human PD-L1.

Engineered Cell‐Derived Vesicles Displaying Targeting Peptide and Functionalized with Nanocarriers for Therapeutic microRNA Delivery to Triple‐Negative Breast Cancer in Mice (Adv. Healthcare Mater. 5/2022)

Correction to "Gold-Nanostar-Chitosan-Mediated Delivery of SARS-CoV-2 DNA Vaccine for Respiratory Mucosal Immunization: Development and Proof-of-Principle".