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Pharmaceutics
Special Issues
Nanomedicine to Enhance Innate and Adaptive Anticancer Immunity
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Nanomedicine to Enhance Innate and Adaptive Anticancer Immunity

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 19294

Special Issue Editors

Dr. Stefano Persano

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Guest Editor
IIT Central Research Labs Genova, Istituto Italiano di Tecnologia (IIT), via Morego 30, 16163 Genova, Italy
Interests: nanovaccines; nanomaterials; cancer immunotherapy; nanomedicine; mRNA-based immunotherapy; drug and gene delivery; non-viral vectors
Prof. Dr. Stefano Leporatti

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Guest Editor
CNR NANOTEC—Istituto di Nanotecnologia, Via Monteroni, 73100 Lecce, Italy
Interests: nanomedicine; drug delivery; scanning force microscopy; cytomechanics; nanocarriers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the last decade, immunotherapy has revolutionized the treatment of cancer. Cancer immunotherapy relies on activation of either innate or adaptive immunity to target and eradicate malignant cells. However, the application of conventional immunotherapies has been limited by their instability and inefficient delivery leading to lack of efficacy and off-target accumulation causing undesired systemic toxicity.

Nanoparticles possess the unique potential to potentiate current immunotherapies by improving their stability, biodistribution, immunogenicity and facilitating the codelivery of different immunotherapeutics for the implementation of more effective combinatorial therapies. To date, a wide number of nanoparticle-based strategies have been successfully proposed for cancer immunotherapy, and they can be roughly categorized in two main groups: (1) Generalized immunotherapies (Immunogenic cell death, Cytokines, Immune adjuvants, Checkpoint inhibitors, Immunosuppressive cell depletion/re-shape), (2) Personalized immunotherapies (Antigen-specific vaccination, Adoptive cell transfer, Monoclonal antibodies).

This special issue welcomes all the original research papers and reviews focusing on different approaches for nanostructure-based cancer immunotherapy aimed to harness innate and/or adaptive immunity for cancer therapy.

Dr. Stefano Persano
Prof. Dr. Stefano Leporatti
Guest Editors

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Keywords

  • cancer immunotherapy
  • nanomedicine
  • vaccine
  • drug delivery
  • nanoparticles
  • immunotherapeutics
  • immunization
  • mrna-based immunotherapy
  • immunogenic cell death (ICD)
  • checkpoint inhibitors
  • CAR cell therapy
  • adoptive immunotherapy
  • monoclonal antibody
  • nanostructures
  • lipid nanoparticles
  • inorganic nanoparticles
  • polymeric nanoparticles

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Published Papers (5 papers)

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Research

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26 pages, 3410 KiB  
Article
The Effect of Curcumin-Loaded Glucan Nanoparticles on Immune Cells: Size as a Critical Quality Attribute
by Mariana Colaço, Tiago Roquito, João Panão Costa, Maria Teresa Cruz and Olga Borges
Pharmaceutics 2023, 15(2), 623; https://doi.org/10.3390/pharmaceutics15020623 - 13 Feb 2023
Cited by 7 | Viewed by 2592
Abstract
Curcumin is known for its multiple health benefits, largely due to its antioxidant and anti-inflammatory properties. It has been extensively studied as a therapeutic agent, however, it does not have good clinical efficacy due to its poor water solubility and bioavailability. Despite accepting [...] Read more.
Curcumin is known for its multiple health benefits, largely due to its antioxidant and anti-inflammatory properties. It has been extensively studied as a therapeutic agent, however, it does not have good clinical efficacy due to its poor water solubility and bioavailability. Despite accepting the encapsulation of this compound in polymeric particles as one of the most promising strategies to increase its therapeutic value, these nanoparticles have fallen short of expectations due to a lack of assessment of their possible adverse effects on the immune system. Therefore, in this work, we report on a new method to encapsulate curcumin into glucan nanoparticles and their effects on cells of the immune system were evaluated. Two different-sized curcumin-loaded glucan NPs (GluCur 100 and GluCur 380) were produced, each with an encapsulation efficiency close to 100%, and were characterized regarding their size distribution, surface properties, and morphology. The results revealed the greatest hemolytic effect and cytotoxicity for the smallest particles (100 nm) tested in human PBMCs and RAW 264.7 cells. Although GluCur 380 NPs showed a weaker ROS production, they were able to inhibit the production of NO by macrophages. Furthermore, we found that the coagulation time was not affected by both sized-particles as well as platelet function. Additionally, both nanoparticles induced lymphocyte proliferation and TNF-α secretion by Mo-DCs. In conclusion, this report emphasizes the importance of the immunotoxicity assessment and how this is dependent on the intrinsic properties of nanomaterials, hopefully contributing to increasing the safety of nanomedicines. Full article
(This article belongs to the Special Issue Nanomedicine to Enhance Innate and Adaptive Anticancer Immunity)
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22 pages, 28084 KiB  
Article
Elucidating the Innate Immunological Effects of Mild Magnetic Hyperthermia on U87 Human Glioblastoma Cells: An In Vitro Study
by Stefano Persano, Francesco Vicini, Alessandro Poggi, Jordi Leonardo Castrillo Fernandez, Giusy Maria Rita Rizzo, Helena Gavilán, Niccolo Silvestri and Teresa Pellegrino
Pharmaceutics 2021, 13(10), 1668; https://doi.org/10.3390/pharmaceutics13101668 - 12 Oct 2021
Cited by 22 | Viewed by 3948
Abstract
Cancer immunotherapies have been approved as standard second-line or in some cases even as first-line treatment for a wide range of cancers. However, immunotherapy has not shown clinically relevant success in glioblastoma (GBM). This is principally due to the brain’s “immune-privileged” status and [...] Read more.
Cancer immunotherapies have been approved as standard second-line or in some cases even as first-line treatment for a wide range of cancers. However, immunotherapy has not shown clinically relevant success in glioblastoma (GBM). This is principally due to the brain’s “immune-privileged” status and the peculiar tumor microenvironment (TME) of GBM characterized by a lack of tumor-infiltrating lymphocytes and the establishment of immunosuppressive mechanisms. Herein, we explore a local mild thermal treatment, generated via cubic-shaped iron oxide magnetic nanoparticles (size ~17 nm) when exposed to an external alternating magnetic field (AMF), to induce immunogenic cell death (ICD) in U87 glioblastoma cells. In accordance with what has been observed with other tumor types, we found that mild magnetic hyperthermia (MHT) modulates the immunological profile of U87 glioblastoma cells by inducing stress-associated signals leading to enhanced phagocytosis and killing of U87 cells by macrophages. At the same time, we demonstrated that mild magnetic hyperthermia on U87 cells has a modulatory effect on the expression of inhibitory and activating NK cell ligands. Interestingly, this alteration in the expression of NK ligands in U87 cells upon MHT treatment increased their susceptibility to NK cell killing and enhanced NK cell functionality. The overall findings demonstrate that mild MHT stimulates ICD and sensitizes GBM cells to NK-mediated killing by inducing the upregulation of specific stress ligands, providing a novel immunotherapeutic approach for GBM treatment, with potential to synergize with existing NK cell-based therapies thus improving their therapeutic outcomes. Full article
(This article belongs to the Special Issue Nanomedicine to Enhance Innate and Adaptive Anticancer Immunity)
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Review

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18 pages, 1015 KiB  
Review
The Potential Use of Exosomes in Anti-Cancer Effect Induced by Polarized Macrophages
by Chizumi Abe, Maharshi Bhaswant, Teruo Miyazawa and Taiki Miyazawa
Pharmaceutics 2023, 15(3), 1024; https://doi.org/10.3390/pharmaceutics15031024 - 22 Mar 2023
Cited by 4 | Viewed by 2640
Abstract
The rapid development of aberrant cells outgrowing their normal bounds, which can subsequently infect other body parts and spread to other organs—a process known as metastasis—is one of the significant characteristics of cancer. The main reason why cancer patients die is because of [...] Read more.
The rapid development of aberrant cells outgrowing their normal bounds, which can subsequently infect other body parts and spread to other organs—a process known as metastasis—is one of the significant characteristics of cancer. The main reason why cancer patients die is because of widespread metastases. This abnormal cell proliferation varies in cancers of over a hundred types, and their response to treatment can vary substantially. Several anti-cancer drugs have been discovered to treat various tumors, yet they still have harmful side-effects. Finding novel, highly efficient targeted therapies based on modifications in the molecular biology of tumor cells is essential to reduce the indiscriminate destruction of healthy cells. Exosomes, an extracellular vesicle, are promising as a drug carrier for cancer therapy due to their good tolerance in the body. In addition, the tumor microenvironment is a potential target to regulate in cancer treatment. Therefore, macrophages are polarized toward M1 and M2 phenotypes, which are involved in cancer proliferation and are malignant. It is evident from recent studies that controlled macrophage polarization might contribute to cancer treatment, by the direct way of using miRNA. This review provides an insight into the potential use of exosomes to develop an ‘indirect’, more natural, and harmless cancer treatment through regulating macrophage polarization. Full article
(This article belongs to the Special Issue Nanomedicine to Enhance Innate and Adaptive Anticancer Immunity)
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24 pages, 7095 KiB  
Review
Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy
by Yujeong Moon, Seong Ik Jeon, Man Kyu Shim and Kwangmeyung Kim
Pharmaceutics 2023, 15(2), 411; https://doi.org/10.3390/pharmaceutics15020411 - 26 Jan 2023
Cited by 14 | Viewed by 4889
Abstract
Proteolysis-targeting chimeras (PROTACs) are rapidly emerging as a potential therapeutic strategy for cancer therapy by inducing the degradation of tumor-overexpressing oncogenic proteins. They can specifically catalyze the degradation of target oncogenic proteins by recruiting E3 ligases and utilizing the ubiquitin-proteasome pathway. Since their [...] Read more.
Proteolysis-targeting chimeras (PROTACs) are rapidly emerging as a potential therapeutic strategy for cancer therapy by inducing the degradation of tumor-overexpressing oncogenic proteins. They can specifically catalyze the degradation of target oncogenic proteins by recruiting E3 ligases and utilizing the ubiquitin-proteasome pathway. Since their mode of action is universal, irreversible, recyclable, long-lasting, and applicable to ‘undruggable’ proteins, PROTACs are gradually replacing the role of conventional small molecular inhibitors. Moreover, their application areas are being expanded to cancer immunotherapy as various types of oncogenic proteins that are involved in immunosuppressive tumor microenvironments. However, poor water solubility and low cell permeability considerably restrict the pharmacokinetic (PK) property, which necessitates the use of appropriate delivery systems for cancer immunotherapy. In this review, the general characteristics, developmental status, and PK of PROTACs are first briefly covered. Next, recent studies on the application of various types of passive or active targeting delivery systems for PROTACs are introduced, and their effects on the PK and tumor-targeting ability of PROTACs are described. Finally, recent drug delivery systems of PROTACs for cancer immunotherapy are summarized. The adoption of an adequate delivery system for PROTAC is expected to accelerate the clinical translation of PROTACs, as well as improve its efficacy for cancer therapy. Full article
(This article belongs to the Special Issue Nanomedicine to Enhance Innate and Adaptive Anticancer Immunity)
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36 pages, 2052 KiB  
Review
Nanomedicine as a Promising Tool to Overcome Immune Escape in Breast Cancer
by Alba Navarro-Ocón, Jose L. Blaya-Cánovas, Araceli López-Tejada, Isabel Blancas, Rosario M. Sánchez-Martín, María J. Garrido, Carmen Griñán-Lisón, Jesús Calahorra, Francisca E. Cara, Francisco Ruiz-Cabello, Juan A. Marchal, Natalia Aptsiauri and Sergio Granados-Principal
Pharmaceutics 2022, 14(3), 505; https://doi.org/10.3390/pharmaceutics14030505 - 25 Feb 2022
Cited by 8 | Viewed by 3457
Abstract
Breast cancer is the most common type of malignancy and leading cause of cancer death among women worldwide. Despite the current revolutionary advances in the field of cancer immunotherapy, clinical response in breast cancer is frequently below expectations, in part due to various [...] Read more.
Breast cancer is the most common type of malignancy and leading cause of cancer death among women worldwide. Despite the current revolutionary advances in the field of cancer immunotherapy, clinical response in breast cancer is frequently below expectations, in part due to various mechanisms of cancer immune escape that produce tumor variants that are resistant to treatment. Thus, a further understanding of the molecular events underlying immune evasion in breast cancer may guarantee a significant improvement in the clinical success of immunotherapy. Furthermore, nanomedicine provides a promising opportunity to enhance the efficacy of cancer immunotherapy by improving the delivery, retention and release of immunostimulatory agents in targeted cells and tumor tissues. Hence, it can be used to overcome tumor immune escape and increase tumor rejection in numerous malignancies, including breast cancer. In this review, we summarize the current status and emerging trends in nanomedicine-based strategies targeting cancer immune evasion and modulating the immunosuppressive tumor microenvironment, including the inhibition of immunosuppressive cells in the tumor area, the activation of dendritic cells and the stimulation of the specific antitumor T-cell response. Full article
(This article belongs to the Special Issue Nanomedicine to Enhance Innate and Adaptive Anticancer Immunity)
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