The application of nano-medicine to overcome the challenges related to immune checkpoint blockades in cancer immunotherapy: Recent advances and opportunities

Sanaei, Mohammad‐Javad; Pourbagheri‐Sigaroodi, Atieh; Kaveh, Vahid; Sheikholeslami, Seyed Amir; Salari, Sina; Bashash, Davood

doi:10.1016/j.critrevonc.2020.103160

Cited by 27 publications

(14 citation statements)

References 212 publications

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“…31,32 Recent advances in nanoparticle-based immune check point inhibitor therapy have improved the anti-tumor immunity against various types of malignancies, including NSCLC. [33][34][35] Our findings reveal that Tregs immunosuppressive signaling can be restrained in both in vivo and ex vivo by using a CuS/EPDA photothermal nanocarrier model. The combinational use of epacadostat, an inhibitor of immunosuppression and IDO-1 and Dasatinib, a multikinase inhibitor that prevents the proliferation and function of CD4 + CD25 + regulatory cells, shows promising results.…”

Section: Discussionmentioning

confidence: 75%

Engineered Hybrid Treg-Targeted Nanosomes Restrain Lung Immunosuppression by Inducing Intratumoral CD8+T Cell Immunity

Domvri¹,

Petanidis²,

Anestakis³

et al. 2022

IJN

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Introduction Tumor immunotherapy is a key therapeutic paradigm for the treatment of several malignancies. However, in metastatic lung cancer, classical immunotherapy regimes are ineffective due to regulatory T cell (Treg)-related immunosuppression and tumor relapse. Materials To address this issue, we designed specific biocompatible Treg-targeted nanocarriers (NCs) as a model of immune-based nanotherapy, in order to target Treg-related immunosuppression in the lung tumor microenvironment. This is achieved through the combination of Dasatinib and Epacadostat integrated into biodegradable nanosomes which can inhibit and reverse Treg-supporting immunosuppression. Flow cytometry and immunofluorescence analysis, PET/CT scan, PTT/PA imaging and the Balb/c tumor model were used to explore the anti-tumor effect of Treg-targeted NCs both in vitro and in vivo. Results Findings reveal that NC treatment triggered substantial tumor cell apoptosis and drastically decreased tumor volume followed by downregulation of Ki-67 antigen expression, respectively. Drug circulation time was also increased as shown by biodistribution analysis accompanied by greater accumulation in lung and peripheral tissues. Intratumoral Th1 cytokines’ expression was also increased, especially TNF-A, IL-12 by 42%, and IL-6 by 18% compared to PBS treatment. In addition, the presence of mature CD80 + /CD86 + dendritic cells (DCs) revealed T cell enrichment and a decline in MDSC infiltration and myeloid subsets. Interestingly, a significant decline of Gr/CD11b myeloid cell population in blood and tissue samples was also observed. This immune activation can be attributed to the enhanced PTT efficiency and tumor targeting ability of the nanospheres which under near infrared (NIR) exposure can prompt highly efficient tumor ablation. We also demonstrated their therapeutic efficacy against 4T1 metastatic breast cancer model. Additionally, the photothermal therapy in combination with PD-L1 checkpoint blockade therapy exerted long-term tumor control over both primary and distant tumors. Discussion Overall, our findings present a novel nano-enabled platform for the inhibition of Treg-dependent immunosuppression in NSCLC and provide a novel nanotherapeutic strategy for the treatment of metastatic neoplasia.

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Section: Discussionmentioning

confidence: 75%

Engineered Hybrid Treg-Targeted Nanosomes Restrain Lung Immunosuppression by Inducing Intratumoral CD8+T Cell Immunity

Domvri¹,

Petanidis²,

Anestakis³

et al. 2022

IJN

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“…To ensure bonding of PD-L1 and ICIs, multivalent poly (amidoamine) dendrimers were employed; as a result, PD-L1 blockade effect was improved, and tumor site drug accumulation was enhanced [ 218 ]. CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) is as an immune checkpoint with the function to downregulate immune responses [ 219 ]. Among these molecules are antibodies, small molecular inhibitors, proteins.…”

Section: Cancer Treatment and Nanomaterials Designmentioning

confidence: 99%

Nanomaterials for cancer therapy: current progress and perspectives

et al. 2021

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Cancer is a disease with complex pathological process. Current chemotherapy faces problems such as lack of specificity, cytotoxicity, induction of multi-drug resistance and stem-like cells growth. Nanomaterials are materials in the nanorange 1–100 nm which possess unique optical, magnetic, and electrical properties. Nanomaterials used in cancer therapy can be classified into several main categories. Targeting cancer cells, tumor microenvironment, and immune system, these nanomaterials have been modified for a wide range of cancer therapies to overcome toxicity and lack of specificity, enhance drug capacity as well as bioavailability. Although the number of studies has been increasing, the number of approved nano-drugs has not increased much over the years. To better improve clinical translation, further research is needed for targeted drug delivery by nano-carriers to reduce toxicity, enhance permeability and retention effects, and minimize the shielding effect of protein corona. This review summarizes novel nanomaterials fabricated in research and clinical use, discusses current limitations and obstacles that hinder the translation from research to clinical use, and provides suggestions for more efficient adoption of nanomaterials in cancer therapy.

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“… 103 Nanotechnology has been used to load synthetic or natural molecules that have a crucial role in restoring the immune system’s anti-tumor function. Small molecular inhibitors, antibodies, and proteins that target programmed cell death protein 1 (PD 1) 104 and cytotoxic T-lymphocyte associated protein 4 (CTLA 4) 105 have shown promising results in recent years. 106 Nanoparticles can be used as vehicles for these immunotherapeutic agents such as cancer vaccines, cytokines, and adoptive cellular therapies to fight cancer.…”

Section: Application Of Nanotechnology For Cancer Diagnosis and Treat...mentioning

confidence: 99%

Nanotechnology: A Promising Approach for Cancer Diagnosis, Therapeutics and Theragnosis

Dessale¹,

Mengistu²,

Mengist³

2022

IJN

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Cancer remains the most devastating disease and the major cause of mortality worldwide. Although early diagnosis and treatment are the key approach in fighting against cancer, the available conventional diagnostic and therapeutic methods are not efficient. Besides, ineffective cancer cell selectivity and toxicity of traditional chemotherapy remain the most significant challenge. These limitations entail the need for the development of both safe and effective cancer diagnosis and treatment options. Due to its robust application, nanotechnology could be a promising method for in-vivo imaging and detection of cancer cells and cancer biomarkers. Nanotechnology could provide a quick, safe, cost-effective, and efficient method for cancer management. It also provides simultaneous diagnosis and treatment of cancer using nano-theragnostic particles that facilitate early detection and selective destruction of cancer cells. Updated and recent discussions are important for selecting the best cancer diagnosis, treatment, and management options, and new insights on designing effective protocols are utmost important. This review discusses the application of nanotechnology in cancer diagnosis, therapeutics, and theragnosis and provides future perspectives in the field.

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The application of nano-medicine to overcome the challenges related to immune checkpoint blockades in cancer immunotherapy: Recent advances and opportunities

Cited by 27 publications

References 212 publications

Engineered Hybrid Treg-Targeted Nanosomes Restrain Lung Immunosuppression by Inducing Intratumoral CD8+T Cell Immunity

Engineered Hybrid Treg-Targeted Nanosomes Restrain Lung Immunosuppression by Inducing Intratumoral CD8+T Cell Immunity

Nanomaterials for cancer therapy: current progress and perspectives

Nanotechnology: A Promising Approach for Cancer Diagnosis, Therapeutics and Theragnosis

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