Induction of immunogenic cell death of cancer cells through nanoparticle-mediated dual chemotherapy and photothermal therapy

Aghda, Niloofar Heshmati; Abdulsahib, Shahad M.; Severson, Carli; Torres-Hurtado, S. A.; Yildiz, Tugba; Castillo, Juan Antonio; Tunnell, James W.; Betancourt, Tania

doi:10.1016/j.ijpharm.2020.119787

Cited by 29 publications

(18 citation statements)

References 52 publications

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“…Similar findings have been recently reported in other PLA-PEGbased drug nanocarriers, demonstrating the potential of nanomedicine for cancer treatment. In particularly, PEG has been shown to enable site-specific delivery of drugs in various cancers (Xue et al, 2018;Duncan et al, 2019;Heshmati Aghda et al, 2020;Lundsten et al, 2020). Furthermore, no significant cytotoxicity of the blank PMs was observed in ALL cells in vitro, even when administered at maximum doses; and we didn't find obvious adverse reactions, such as gastrointestinal reactions, neurotoxicity, hepatoxicity and bone marrow suppression in the animals following DOX-PMs-NPMBP treatment.…”

Section: Discussionmentioning

confidence: 67%

Doxorubicin/Nucleophosmin Binding Protein-Conjugated Nanoparticle Enhances Anti-leukemia Activity in Acute Lymphoblastic Leukemia Cells in vitro and in vivo

Gan

Chen

et al. 2021

Front. Pharmacol.

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Acute lymphoblastic leukemia (ALL) is an aggressive malignancy. Adults with ALL have more than 50% relapse rates. We have previously validated that overexpression of nucleophosmin (NPM) is involved in the multidrug resistance (MDR) development during ALL; and a synthetically engineered recombinant NPM binding protein (NPMBP) has been developed in our group; NPMBP and doxorubicin (DOX) can be conjugated in a nanoparticle-based drug delivery system named DOX-PMs-NPMBP to counteract MDR during ALL. Here, we evaluated the antileukemia potential of DOX-PMs-NPMBP in resistant ALL cells. This study demonstrates that DOX-PMs-NPMBP significantly enhances chemosensitivity to DOX in ALL cells. Despite at variable concentrations, both resistant and primary ALL cells from relapsed patients were sensitive to DOX-PMs-NPMBP. In detail, the half maximal inhibitory concentration (IC50) values of DOX-PMs-NPMBP were between 1.6- and 7.0-fold lower than those of DOX in cell lines and primary ALL cells, respectively; and apoptotic cells ratio was over 2-fold higher in DOX-PMs-NPMBP than DOX. Mechanistically, p53-driven apoptosis induction and cell cycle arrest played essential role in DOX-PMs-NPMBP-induced anti-leukemia effects. Moreover, DOX-PMs-NPMBP significantly inhibited tumor growth and prolonged mouse survival of ALL xenograft models; and no systemic toxicity occurrence was observed after treatment during follow-up. In conclusion, these data indicate that DOX-PMs-NPMBP may significantly exert growth inhibition and apoptosis induction, and markedly improve DOX antileukemia activity in resistant ALL cells. This novel drug delivery system may be valuable to develop as a new therapeutic strategy against multidrug resistant ALL.

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Section: Discussionmentioning

confidence: 67%

Doxorubicin/Nucleophosmin Binding Protein-Conjugated Nanoparticle Enhances Anti-leukemia Activity in Acute Lymphoblastic Leukemia Cells in vitro and in vivo

Gan

Chen

et al. 2021

Front. Pharmacol.

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“…However, exposure to CRT was observed in BC cell lines after docetaxel intervention, and antitumor immunity was reinforced mainly by the increased antigen presenting capacity and translocation of CRT (41). In vitro studies indicated that paclitaxel, gemcitabine and doxorubicinmediated chemotherapy could efficiently kill cancer cells and lead to a high level of DAMP (CRT and HMGB1) (65)(66)(67). It has been shown that cyclophosphamide analogues improved tumor immunogenicity by facilitating the release of ICD markers (CRT, HMGB1, and ATP) (43).…”

Section: Chemotherapy-induced Alterations Of Damage-associated Molecular Patterns (Damps)mentioning

confidence: 99%

Immunostimulatory Properties of Chemotherapy in Breast Cancer: From Immunogenic Modulation Mechanisms to Clinical Practice

et al. 2022

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Breast cancer (BC) is the most common malignancy among females. Chemotherapy drugs remain the cornerstone of treatment of BC and undergo significant shifts over the past 100 years. The advent of immunotherapy presents promising opportunities and constitutes a significant complementary to existing therapeutic strategies for BC. Chemotherapy as a cytotoxic treatment that targets proliferation malignant cells has recently been shown as an effective immune-stimulus in multiple ways. Chemotherapeutic drugs can cause the release of damage-associated molecular patterns (DAMPs) from dying tumor cells, which result in long-lasting antitumor immunity by the key process of immunogenic cell death (ICD). Furthermore, Off-target effects of chemotherapy on immune cell subsets mainly involve activation of immune effector cells including natural killer (NK) cells, dendritic cells (DCs), and cytotoxic T cells, and depletion of immunosuppressive cells including Treg cells, M2 macrophages and myeloid-derived suppressor cells (MDSCs). Current mini-review summarized recent large clinical trials regarding the combination of chemotherapy and immunotherapy in BC and addressed the molecular mechanisms of immunostimulatory properties of chemotherapy in BC. The purpose of our work was to explore the immune-stimulating effects of chemotherapy at the molecular level based on the evidence from clinical trials, which might be a rationale for combinations of chemotherapy and immunotherapy in BC.

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“…The selected NP concentration range is in accordance with the literature. [29][30][31] After 1.5 h incubation of cells with NPs at 37 °C, the cell media was replaced with fresh media, and cells were treated with an 808-nm laser (2 W cm − 2, laser power = 0.74 W, spot diameter = 7 mm) for 2.5 min in a chamber at 37 °C and returned to the incubator.…”

Section: Effect Of Treatment On Cell Viabilitymentioning

confidence: 99%

“…Selection of BSA as the carrier led to higher DL% for both agents is compared to our previous work where we utilized poly(lactic acid)-b-poly(ethylene glycol) as the carrier. [29]…”

Section: Nanoparticle Preparation and Agent Loadingmentioning

confidence: 99%

Dual Photothermal/Chemotherapy of Melanoma Cells with Albumin Nanoparticles Carrying Indocyanine Green and Doxorubicin Leads to Immunogenic Cell Death

Aghda

Torres-Hurtado

Abdulsahib

et al. 2021

Macromolecular Bioscience

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Recent focus on cancer immunotherapies has led to significant interest in the development of therapeutic strategies that can lead to immunogenic cell death (ICD), which can cause activation of an immune response against tumor cells and improve immunotherapy outcomes by enhancing the immunogenicity of the tumor microenvironment. In this work, a nanomedicine-mediated combination therapy is used to deliver the ICD inducers doxorubicin (Dox), a chemotherapeutic agent, and indocyanine green (ICG), a photothermal agent. These agents are loaded into nanoparticles (NPs) of bovine serum albumin (BSA) that are prepared through a desolvation process. The formulation of BSA NPs is optimized to achieve NPs of 102.6 nm in size and loadings of 8.55 % and 5.69 % (w/w) for ICG and Dox, respectively. The controlled release of these agents from the BSA NPs is confirmed. Upon laser irradiation for 2.5 min, NPs at a dose of 62.5 𝝁g mL −1 are able to increase the temperature of the cells by 7 °C and thereby inhibit the growth of B16F10 melanoma cells in vitro. Surface presentation of heat shock proteins and calreticulin from the cells after treatment confirmed the ability of the Dox/ICG loaded BSA NPs to induce ICD in the melanoma cells.

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Induction of immunogenic cell death of cancer cells through nanoparticle-mediated dual chemotherapy and photothermal therapy

Cited by 29 publications

References 52 publications

Doxorubicin/Nucleophosmin Binding Protein-Conjugated Nanoparticle Enhances Anti-leukemia Activity in Acute Lymphoblastic Leukemia Cells in vitro and in vivo

Doxorubicin/Nucleophosmin Binding Protein-Conjugated Nanoparticle Enhances Anti-leukemia Activity in Acute Lymphoblastic Leukemia Cells in vitro and in vivo

Immunostimulatory Properties of Chemotherapy in Breast Cancer: From Immunogenic Modulation Mechanisms to Clinical Practice

Dual Photothermal/Chemotherapy of Melanoma Cells with Albumin Nanoparticles Carrying Indocyanine Green and Doxorubicin Leads to Immunogenic Cell Death

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