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Cancer therapy requires sophisticated treatment strategies to obtain the highest success. Nanotechnology is enabling, revolutionizing, and multidisciplinary concepts to improve conventional cancer treatment modalities. Nanomaterials have a central role in this scenario, explaining why various nanomaterials are currently being developed for cancer therapy. Viral nanoparticles (VNPs) have shown promising performance in cancer therapy due to their unique features. VNPs possess morphological homogeneity, ease of functionalization, biocompatibility, biodegradability, water solubility, and high absorption efficiency that are beneficial for cancer therapy applications. In the current review paper, we highlight state‐of‐the‐art properties and potentials of plant viruses, strategies for multifunctional plant VNPs formulations, potential applications and challenges in VNPs‐based cancer therapy, and finally practical solutions to bring potential cancer therapy one step closer to real applications. This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseNanotechnology Approaches to Biology > Nanoscale Systems in BiologyBiology‐Inspired Nanomaterials > Protein and Virus‐Based Structures [ABSTRACT FROM AUTHOR]

Plant virus nanoparticles (PVNPs) have garnered considerable interest as a promising nanotechnology approach to combat cancer. Owing to their biocompatibility, stability, and adjustable surface functionality, PVNPs hold tremendous potential for both therapeutic and imaging applications. The versatility of PVNPs is evident from their ability to be tailored to transport a range of therapeutic agents, including chemotherapy drugs, siRNA, and immunomodulators, thereby facilitating targeted delivery to the tumor microenvironment (TME). Furthermore, PVNPs may be customized with targeting ligands to selectively bind to cancer cell receptors, reducing off-target effects. Additionally, PVNPs possess immunogenic properties and can be engineered to exhibit tumor-associated antigens, thereby stimulating anti-tumor immune responses. In conclusion, the potential of PVNPs as a versatile platform for fighting cancer is immense, and further research is required to fully explore their potential and translate them into clinical applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor cell-derived extracellular vesicles (TEVs) are an important means of tumor communication with, and manipulation of, the patient's physiology. TEVs influence the local tumor environment as well as the systemic conditions of the patient. Progressive changes in tumor interactions with the host immune system are defined as "immunoediting". Here, we summarize TEV effects on the immune system during the stages of cancer immunoediting and outline the molecular and cellular characteristics of interactions that result in complete tumor regression versus tumor immune escape and progression. Generally, the cargo profile of TEVs naturally changes during immunoediting toward immunosuppression while different cell stress or treatment conditions can inhibit this process or even reverse it to immunostimulation by altering the TEVs cargos. Therefore, understanding potential immunotherapeutic properties and how they can be manipulated to treat cancer should be considered a new research approach in oncoimmunotherapy. The tumor microenvironment (TME) within and around a tumor is a complex interacting mixture of tumor cells with various stromal cells, including endothelial cells, fibroblasts, and immune cells. In the early steps of tumor formation, the local microenvironment tends to oppose carcinogenesis, while with cancer progression, the microenvironment skews into a protumoral TME and the tumor influences stromal cells to provide tumor-supporting functions. The creation and development of cancer are dependent on escape from immune recognition predominantly by influencing stromal cells, particularly immune cells, to suppress antitumor immunity. This overall process is generally called immunoediting and has been categorized into three phases; elimination, equilibrium, and escape. Interaction of tumor cells with stromal cells in the TME is mediated generally by cell-to-cell contact, cytokines, growth factors, and extracellular vesicles (EVs). The least well studied are EVs (especially exosomes), which are nanoparticle-sized bilayer membrane vesicles released by many cell types that participate in cell/cell communication. EVs carry various proteins, nucleic acids, lipids, and small molecules that influence cells that ingest the EVs. Tumor-derived extracellular vesicles (TEVs) play a significant role in every stage of immunoediting, and their cargoes change from immune-activating in the early stages of immunoediting into immunosuppressing in the escape phase. In addition, their cargos change with different treatments or stress conditions and can be influenced to be more immune stimulatory against cancer. This review focuses on the emerging understanding of how TEVs affect the differentiation and effector functions of stromal cells and their role in immunoediting, from the early stages of immunoediting to immune escape. Consideration of how TEVs can be therapeutically utilized includes different treatments that can modify TEV to support cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Cancer therapy requires sophisticated treatment strategies to obtain the highest success. Nanotechnology is enabling, revolutionizing, and multidisciplinary concepts to improve conventional cancer treatment modalities. Nanomaterials have a central role in this scenario, explaining why various nanomaterials are currently being developed for cancer therapy. Viral nanoparticles (VNPs) have shown promising performance in cancer therapy due to their unique features. VNPs possess morphological homogeneity, ease of functionalization, biocompatibility, biodegradability, water solubility, and high absorption efficiency that are beneficial for cancer therapy applications. In the current review paper, we highlight state-of-the-art properties and potentials of plant viruses, strategies for multifunctional plant VNPs formulations, potential applications and challenges in VNPs-based cancer therapy, and finally practical solutions to bring potential cancer therapy one step closer to real applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Protein and Virus-Based Structures., (© 2022 Wiley Periodicals LLC.)

Cancer immunotherapies using plant virus nanoparticles (PVNPs) have achieved considerable success in preclinical studies. PVNP based nanoplatforms can be endogenous immune adjuvants and act as nanocarriers that stabilize and deliver cancer antigens and exogenous immune adjuvants. Although they do not infect mammalian cells, PVNPs are viruses and they are variably recognized by pathogen pattern recognition receptors (PRR), activate innate immune cells including antigen-presenting cells (APCs), and increase the expression of costimulatory molecules. Novel immunotherapy strategies use them as in situ vaccines (ISV) that can effectively inhibit tumor growth after intratumoral administration and generate expanded systemic antitumor immunity. PVNPs combined with other tumor immunotherapeutic options and other modalities of oncotherapy can improve both local and systemic anti-tumor immune responses. While not yet in clinical trials in humans, there is accelerating interest and research of the potential of PVNPs for ISV immune therapy for cancer. Thus, antitumor efficacy of PVNPs by themselves, or loaded with soluble toll-like receptor (TLR) agonists and/or cancer antigens, will likely enter human trials over the next few years and potentially contribute to next-generation antitumor immune-based therapies., Competing Interests: Conflict of Interest Dr. Fiering is cofounder and has a financial interest in Mosaic Immunoengineering Inc.

Astragalus gossypinus Fischer with wide distribution in Iran belongs to the genus Astragalus (Fabaceae). According to existing references and information, individuals of this species are present in many stations with different ecological conditions. This study carried out for determination and discrimination of intraspecific diversity of Astragalus gossypinus by Eco-phytosociological method from west of Iran. In this method, the principle of data collecting and analyzing based on floristical composition (as floristical markers) of each Endogenous milieu (as the unit of study in Eco-phytosociological method). In this order, application of Endogenous milieu (special station) for data collecting and then their analyzing permit us only determine existence of inter and intraspecific diversity. Then for determinating kind and level of intraspecific diversity (Ecophene, Chemotype, Cytotype, Ecotype ...), can use other studies such as: morphological, anatomical, phytochemical, cytological and etc. In this survey, 29 special stations were studied and 195 species distinguished as companions for Astragalus gossypinus. Then floristic-ecologic data collected from each 29 special stations and analyzed by Anaphyto software (F.C.A, A.H.C, B.O, Marquag methods). Comparison of obtained results on multiple coordinate axes from F.C.A method with results from B.O, Marquag and A.H.C methods led to determination of 7 main groups of Endogenous milieus (special station). Flavonoid analyses were used for determinating kind and level of intraspecific diversity in 7 discriminated groups. Leaves flavonoid components of all collected individuals of Astragalus gossypinus were investigated by TLC method. Obtained data from flavonoid survey analyzed by SPSS and MVSP package with WARD and UPGMA methods. Finally, the results of flavonoid studies confirmed the same 7 groups that identified by floristical composition study and showed intraspecific diversity in chemotype level. So according to these results, we can introduce 7 chemotypes for Astragalus gossypinus from west of Iran. These chemotypes exist in different stations with various ecological conditions.