Oxygen-carrying nanoparticle-based chemo-sonodynamic therapy for tumor suppression and autoimmunity activation

Zhang, Yanan; Qiu, Na; Yan, Hong; Ji, Jianbo; Xi, Yang; Yang, Xiaoye; Zhao, Xiaogang; Zhai, Guangxi

doi:10.1039/d1bm00198a

Cited by 33 publications

(30 citation statements)

References 51 publications

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“…The high infiltration of immune cells into tumor tissues is essential for effective immunotherapy (Qiu et al., 2022 ). Pro-inflammatory cytokines play important roles in coordinating cell-mediated immune responses and regulating the immune system (Zhang et al., 2021 ). TNF-α can promote the expression of major histocompatibility complex class I and intercellular adhesion molecules, cooperate with IFN-γ to induce the expression of major histocompatibility complex class II, initiate T cell-mediated cellular immunity, and enhance the cellular activity of T cells, natural killer cells, lymphokine-activated killer cells, and tumor-infiltrating lymphocytes (Jewett et al., 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Icaritin-loaded PLGA nanoparticles activate immunogenic cell death and facilitate tumor recruitment in mice with gastric cancer

et al. 2022

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This study aimed to explore the anti-tumor effect of icaritin loading poly (lactic-co-glycolic acid) nanoparticles (refer to PLGA@Icaritin NPs) on gastric cancer (GC) cells. Transmission Electron Microscope (TEM), size distribution, zeta potential, drug-loading capability, and other physicochemical characteristics of PLGA@Icaritin NPs were carried out. Furthermore, flow cytometry, confocal laser scanning microscope (CLSM), Cell Counting Kit-8 (CCK-8), Transwell, Elisa assay and Balb/c mice were applied to explore the cellular uptake, anti-proliferation, anti-metastasis, immune response activation effects, and related anti-tumor mechanism of PLGA@Icaritin NPs in vitro and in vivo . PLGA@Icaritin NPs showed spherical shape, with appropriate particle sizes and well drug loading and releasing capacities. Flow cytometry and CLSM results indicated that PLGA@Icaritin could efficiently enter into GC cells. CCK-8 proved that PLGA@Icaritin NPs dramatically suppressed cell growth, induced Lactic dehydrogenase (LDH) leakage, arrested more GC cells at G2 phase, and inhibited the invasion and metastasis of GC cells, compared to free icaritin. In addition, PLGA@Icaritin could help generate dozens of reactive oxygen species (ROS) within GC cells, following by significant mitochondrial membrane potentials (MMPs) loss and excessive production of oxidative-mitochondrial DNA (Ox-mitoDNA). Since that, Ox-mitoDNA further activated the releasing of damage associated molecular pattern molecules (DAMPs), and finally led to immunogenic cell death (ICD). Our in vivo data also elaborated that PLGA@Icaritin exerted a powerful inhibitory effect (∼80%), compared to free icaritin (∼60%). Most importantly, our results demonstrated that PLGA@Icaritin could activate the anti-tumor immunity via recruitment of infiltrating CD4+ cells, CD8+ T cells and increased secretion of cytokine immune factors, including interferon-γ (IFN-γ) tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1). ++ Our findings validate that the successful design of PLGA@Icaritin, which can effectively active ICD and facilitate tumor recruitment in GC through inducing mitoDNA oxidative damage.

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Section: Resultsmentioning

confidence: 99%

Icaritin-loaded PLGA nanoparticles activate immunogenic cell death and facilitate tumor recruitment in mice with gastric cancer

et al. 2022

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“…Unlike photodynamic and sonodynamic therapy, CDT requires neither external energy nor oxygen. Hence, free radical-mediated tumour therapy has a far wider application range than other modalities [ 10 , 11 ]. Cancer cells with therapy-resistant states are relatively more sensitive to ferroptosis than those without them [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis

Zhou

et al. 2021

J Nanobiotechnol

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Background Hepatocellular carcinoma is insensitive to many chemotherapeutic agents. Ferroptosis is a form of programmed cell death with a Fenton reaction mechanism. It converts endogenous hydrogen peroxide into highly toxic hydroxyl radicals, which inhibit hepatocellular carcinoma progression. Methods The morphology, elemental composition, and tumour microenvironment responses of various organic/inorganic nanoplatforms were characterised by different analytical methods. Their in vivo and in vitro tumour-targeting efficacy and imaging capability were analysed by magnetic resonance imaging. Confocal microscopy, flow cytometry, and western blotting were used to investigate the therapeutic efficacy and mechanisms of complementary ferroptosis/apoptosis mediated by the nanoplatforms. Results The nanoplatform consisted of a silica shell doped with iron and disulphide bonds and an etched core loaded with doxorubicin that generates hydrogen peroxide in situ and enhances ferroptosis. It relied upon transferrin for targeted drug delivery and could be activated by the tumour microenvironment. Glutathione-responsive biodegradability could operate synergistically with the therapeutic interaction between doxorubicin and iron and induce tumour cell death through complementary ferroptosis and apoptosis. The nanoplatform also has a superparamagnetic framework that could serve to guide and monitor treatment under T2-weighted magnetic resonance imaging. Conclusion This rationally designed nanoplatform is expected to integrate cancer diagnosis, treatment, and monitoring and provide a novel clinical antitumour therapeutic strategy. Graphical Abstract

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“… 14 , 44 In addition, the hypoxic environment in solid tumors may weaken the antitumor efficacy of PDT or SDT via the hypoxia-activated HIF-1α survival pathway. 11 , 22 In general, it is believed that the downregulation of HIF-1α can improve therapeutic efficacy. 23 The HIF-1α signaling pathway was also considered to reveal possible changes in the oxygen levels in the tumor tissue after treatment.…”

Section: Resultsmentioning

confidence: 99%

“…However, hypoxia and a reducing tumor microenvironment pose a significant challenge in applying SDT and other synergistic therapies. 11 , 12 Hypoxia is a common feature of solid tumors that develops because of an imbalance between the rapid growth of the tumor and abnormal blood vessel supply. 13 Another cause of hypoxia is the overconsumption of oxygen when SDT is applied.…”

Section: Introductionmentioning

confidence: 99%

One-Step Fabrication of Multifunctional PLGA-HMME-DTX@MnO2 Nanoparticles for Enhanced Chemo-Sonodynamic Antitumor Treatment

Cao¹,

Zheng²,

Sun³

et al. 2022

IJN

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Background Sonodynamic therapy (SDT) and its synergistic cancer therapy derivatives, such as combined chemotherapy-SDT (chemo-SDT), are promising approaches for tumor treatment. However, the main drawbacks restricting their applications are hypoxia in tumors and the reducing microenvironment or high glutathione (GSH) levels. Methods In this study, a hybrid metal MnO 2 was deposited onto nanoparticles fabricated using poly(lactic-co-glycolic acid) (PLGA), carrying docetaxel (DTX) and the sonosensitizer hematoporphyrin monomethyl ether (HMME) (PHD@MnO 2 ) via a one-step flash nanoprecipitation (FNP) method. Characterization and in vitro and in vivo experiments were conducted to explore the chemo-SDT effect of PHD@MnO 2 and evaluate the synergetic antitumor treatment of this nanosystem. Results When low-power ultrasound is applied, the acquired PHD@MnO 2 , whether in solution or in MCF-7 cells, generated ROS more efficiently than other groups without MnO 2 or those treated via monotherapy. Specifically, GSH-depletion was observed when MnO 2 was introduced into the system. PHD@MnO 2 presented good biocompatibility and biosafety in vitro and in vivo. These results indicated that the PHD@MnO 2 nanoparticles overcame hypoxia in tumor tissue and suppressed the expression of hypoxia-inducible factor 1 alpha (HIF-1α), achieving enhanced chemo-SDT. Conclusion This study provides a paradigm that rationally engineered multifunctional metal-hybrid nanoparticles can serve as an effective platform for augmenting the antitumor therapeutic efficiency of chemo-SDT.

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Oxygen-carrying nanoparticle-based chemo-sonodynamic therapy for tumor suppression and autoimmunity activation

Abstract: Sonodynamic therapy (SDT) is a promising non-invasive approach for cancer therapy. However, tumor hypoxia, a pathological characteristic of most solid tumor types, poses a major challenge in application of SDT. In this...

Cited by 33 publications

References 51 publications

Icaritin-loaded PLGA nanoparticles activate immunogenic cell death and facilitate tumor recruitment in mice with gastric cancer

Icaritin-loaded PLGA nanoparticles activate immunogenic cell death and facilitate tumor recruitment in mice with gastric cancer

Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis

One-Step Fabrication of Multifunctional PLGA-HMME-DTX@MnO2 Nanoparticles for Enhanced Chemo-Sonodynamic Antitumor Treatment

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