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Organic Sonodynamic Materials for Combination Cancer Immunotherapy

ADVANCED MATERIALS (2023)

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Emerging Sonodynamic Therapy-Based Nanomedicines for Cancer Immunotherapy

Yunrong Yang et al.

Summary: The article systematically summarizes the characteristics of the tumor immune microenvironment and the mechanisms of immunogenic cell death (ICD). It also discusses the therapeutic mechanism, advantages, and limitations of sonodynamic therapy (SDT) in promoting cancer immunotherapy. Furthermore, it highlights the recent advances of SDT-based nanomedicines in this field. Finally, it explores the application prospects and challenges of SDT-based immunotherapy in future clinical translation.

ADVANCED SCIENCE (2023)

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Article Chemistry, Multidisciplinary

Engineering Macrophage Exosome Disguised Biodegradable Nanoplatform for Enhanced Sonodynamic Therapy of Glioblastoma

Tingting Wu et al.

Summary: Sonodynamic therapy (SDT) is a promising cancer treatment modality for glioblastoma (GBM) due to its high tissue penetration and minimal damage to normal tissues. However, the blood-brain barrier (BBB) and hypoxic microenvironment present challenges to SDT efficiency. In this study, a biodegradable nanoplatform (CSI@Ex-A) was developed, which could effectively penetrate the BBB and target cancer cells. The nanoplatform releases hydrogen peroxide (H2O2) and oxygen (O-2) to relieve tumor hypoxia, thereby enhancing the efficacy of SDT.

ADVANCED MATERIALS (2022)

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Article Engineering, Biomedical

Perfluorocarbon loaded fluorinated covalent organic polymers with effective sonosensitization and tumor hypoxia relief enable synergistic sonodynamic-immunotherapy

Zhijuan Yang et al.

Summary: This study presents a multifunctional nano-sonosensitizer PFCE@THPPpf-COPs, capable of alleviating tumor hypoxia and immunosuppression, and synergistically suppressing tumor growth by priming host's antitumor immunity, particularly in combination with anti-CD47 immunotherapy.

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Review Nanoscience & Nanotechnology

Regulating trained immunity with nanomedicine

Mandy M. T. van Leent et al.

Summary: This Review discusses nanomedicine platforms to therapeutically regulate trained immunity for the treatment of various conditions, including cancer, inflammation and infection.

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Article Chemistry, Multidisciplinary

Activatable Cancer Sono-Immunotherapy using Semiconducting Polymer Nanobodies

Ziling Zeng et al.

Summary: This study reports the development of semiconducting polymers as efficient sonosensitizers and the further development of sono-immunotherapeutic nanobodies. The strategy can achieve immunogenic cell death, release of anti-CTLA-4 antibodies, and promote tumor-killing function through sono-irradiation, providing important insights for precise spatiotemporal control over immunotherapy.

ADVANCED MATERIALS (2022)

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Article Chemistry, Multidisciplinary

A Dual-Locked Activatable Phototheranostic Probe for Biomarker-Regulated Photodynamic and Photothermal Cancer Therapy

Xin Wei et al.

Summary: This study reports a dual-locked activatable phototheranostic probe that can activate fluorescence signals and switch between photodynamic therapy and photothermal therapy for precise cancer treatment.

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Article Engineering, Biomedical

Immunogenic nanomedicine based on GSH-responsive nanoscale covalent organic polymers for chemo-sonodynamic therapy

Fengyun Shen et al.

Summary: Researchers have synthesized a covalent organic polymer with good physiological stability and sonosensitization efficacy through esterification of a water insoluble sonosensitizer with a oxaliplatin prodrug and PEG. This polymer can induce effective immunogenic cancer cell death under ultrasound exposure and also be used for real-time tracking of dyes and radioisotopes in disease tissues, enhancing the treatment outcome of SDT.

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Manganese-phenolic nanoadjuvant combines sonodynamic therapy with cGAS-STING activation for enhanced cancer immunotherapy

Hao Tian et al.

Summary: A phenolic nanoadjuvant has been developed to enhance the maturation of dendritic cells (DCs) and improve the efficacy of cancer immunotherapy. This nanoadjuvant promotes the activation of the cGAS-STING pathway and sensitizes tumors to PD-L1 checkpoint blockade immunotherapy, resulting in inhibiting tumor growth and restraining lung metastasis.

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Unimolecule-based size-charge switchable nanomedicine for deep cancer sono-immunotherapy

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Summary: This study engineered an anti-programmed death ligand 1 peptide inhibitor (APP) to act in the inner core of unimolecular polymers, which could form size-charge switchable nanomicelles in an acidic tumor microenvironment. Under fluorescence/photoacoustic imaging guidance, these nanomicelles could control the exposure of APP and induce reactive oxygen species (ROS) for immune T-cell recruitment and activation in deep solid tumors.

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Self-Delivering Nanodrugs Developed via Small-Molecule-Directed Assembly and Macrophage Cloaking for Sonodynamic-Augmented Immunotherapy

Fang Xie et al.

Summary: A self-delivering nanodrug system is developed for sonodynamic-augmented immunotherapy, which can efficiently release sonosensitizers and immunomodulators within tumors. By inducing immunogenic cell death, activating tumor-specific effector T cells, and reversing the immunosuppressive tumor microenvironment, this nanodrug system significantly inhibits tumor growth with little systemic toxicity.

ADVANCED HEALTHCARE MATERIALS (2022)

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A novel near-infrared trifluoromethyl heptamethine cyanine dye with mitochondria-targeting for integration of collaborative treatment of photothermal and sonodynamic therapy

Haoran Shi et al.

Summary: A newly designed near-infrared trifluoromethyl-heptamethine cyanine (TFHC) dye was synthesized, which can serve as a mitochondrial-targeting sonosensitizer for sonodynamic therapy and a photothermal therapy agent for photothermal therapy. TFHC has good biocompatibility and can efficiently kill cancer cells under near-infrared and ultrasound irradiation without significant side effects.

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Ultrasound-mediated immune regulation in tumor immunotherapy

S. Sun et al.

Summary: Ultrasound-mediated tumor immunotherapy shows promise in enhancing the body's immune response and inhibiting immune escape. However, challenges such as low response rate and immune-related adverse events need to be addressed.

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Immunosonodynamic Therapy Designed with Activatable Sonosensitizer and Immune Stimulant Imiquimod

Huali Lei et al.

Summary: This study presents the concept of a next-generation sonodynamic sensitizer preparation for immunosonodynamic therapy (iSDT) as a noninvasive synergistic therapeutic modality. By combining sonodynamic therapy and immunotherapy, this method achieves efficient and targeted treatment for tumors. The iSDT specifically activates the sonodynamic effect at the tumor site, showing high specificity in killing tumor cells. Additionally, when combined with an alpha-PD-L1 antibody, this therapy effectively inhibits tumor metastasis.

ACS NANO (2022)

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Catalytical nano-immunocomplexes for remote-controlled sono-metabolic checkpoint trimodal cancer therapy

Chi Zhang et al.

Summary: The authors have developed a pH-responsive and sono-irradiation activatable nanosystem for sono-metabolic cancer immunotherapy, functionalized with anti-PD-L1 and adenosine deaminase. This system can efficiently activate immune effector cells and inhibit immune suppressor cells.

NATURE COMMUNICATIONS (2022)

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Precision cancer sono-immunotherapy using deep-tissue activatable semiconducting polymer immunomodulatory nanoparticles

Jingchao Li et al.

Summary: This study develops a nanomedicine-based cancer sono-immunotherapy that utilizes a semiconducting polymer to generate high levels of 1O2 and conjugates immunomodulators for targeted tumor treatment. The therapy not only reduces tumors and enhances tumor immunogenicity, but also releases immunomodulators specifically at the tumor site. It shows effective antitumor efficacy and reduces immune-related adverse events in animal models.

NATURE COMMUNICATIONS (2022)

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Degradable Multifunctional Porphyrin-Based Porous Organic Polymer Nanosonosensitizer for Tumor-Specific Sonodynamic, Chemo- and

Meiting Li et al.

Summary: Sonodynamic therapy (SDT) is a noninvasive and deep tissue penetrable treatment method that utilizes reactive oxygen species (ROS) for tumor treatment. However, current sonosensitizers face challenges such as low tumor accumulation, insufficient ROS generation, and non-biodegradability. In this study, a degradable multifunctional nanosonosensitizer was constructed using sonosensitive porphyrin building blocks and glutathione (GSH)-responsive disulfide bonds. This nanosonosensitizer achieved tumor target accumulation, GSH-triggered drug release, and low-frequency ultrasound-activated ROS generation. It also effectively induced immunogenic cell death response through the combination of SDT and chemotherapy. This study provides a new strategy for designing and constructing sonosensitizers for triple treatment modalities to eradicate tumors.

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Porphyrin-Based Covalent Organic Framework for Imaging-Guided Cancer Combinatorial Immuno-Sonodynamic Therapy

Zhixiang Lu et al.

Summary: This study presents the synthesis of a covalent organic framework with sonosensitive properties for the efficient loading of MnO2 and Poly(I:C). The developed nanomaterial is capable of reversing the reductive tumor microenvironment, generating magnetic resonance imaging signals, promoting reactive oxygen species production, inducing immunogenic cell death, and boosting the immune response. This multifunctional nanosystem represents a promising strategy for cancer therapy.

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Evoking tumor associated macrophages by mitochondria-targeted magnetothermal immunogenic cell death for cancer immunotherapy

Han Jiang et al.

Summary: This study proposes a novel immunogenic cell death (ICD) modality based on mitochondrial heat stress by magnetic hyperthermia treatment (MHT), which effectively evokes tumor-associated macrophages (TAMs) against cancer cells. A nanomedicine named MRT is synthesized for mitochondria-targeted heat stress-induced oxidative damage of tumor cells, leading to the release of damage-associated molecular patterns (DAMPs) and the activation of TAMs-mediated immune response against cancer cells.

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The expanding role for small molecules in immuno-oncology

Rienk Offringa et al.

Summary: This review provides an update on the application of small-molecule drugs in immuno-oncology, focusing on their use in stimulating the antitumour immune response and targeting T cell checkpoints. The review highlights the combination of antibody-based immune checkpoint inhibitors with small molecules, as well as the recent milestones and hurdles in this field of drug development.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Rational Nanomedicine Design Enhances Clinically Physical Treatment-Inspired or Combined Immunotherapy

Qiaoqiao Liu et al.

Summary: This paper introduces the use of nanomedicine to enhance immune activation and potential, as well as the efficiency improvement of physical treatment on tumor progression, relapse, and metastasis.

ADVANCED SCIENCE (2022)

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Article Multidisciplinary Sciences

Nanocatalytic bacteria disintegration reverses immunosuppression of colorectal cancer

Han Jiang et al.

Summary: A nanocatalytic tumor-immunotherapeutic modality based on bacteria-specific oxidative damage under magnetic hyperthermia (MH) reverses immunosuppression of tumor microenvironment and achieves excellent therapeutic efficacy in an orthotopic colorectal cancer model.

NATIONAL SCIENCE REVIEW (2022)

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Review Chemistry, Physical

Activating Nanomedicines with Electromagnetic Energy for Deep-Tissue Induction of Immunogenic Cell Death in Cancer Immunotherapy

Fengshuo Wang et al.

Summary: The combination of nanomedicines and deep-tissue electromagnetic energy can enhance immunogenic cell death and cancer immunotherapy. Ultrasound, X-ray, magnetic field, and microwave have excellent tissue penetration depths and can effectively induce immunogenic cell death.

SMALL METHODS (2022)

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Article Chemistry, Multidisciplinary

Nanobubble-based anti-hepatocellular carcinoma therapy combining immune check inhibitors and sonodynamic therapy

Yun Liu et al.

Summary: Nanobubbles carrying immune check inhibitors and sonodynamic agents were prepared to inhibit hepatocellular carcinoma (HCC) growth by regulating immune cell function and inducing immunogenic tumor cell death. These nanobubbles showed promising potential in enhancing anti-cancer immune responses.

NANOSCALE ADVANCES (2022)

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Review Chemistry, Multidisciplinary

Electromagnetic Nanomedicines for Combinational Cancer Immunotherapy

Jingchao Li et al.

Summary: Immunotherapy harnesses the immune system to eliminate malignant cells, but faces challenges such as limited patient response rates and immune-related adverse events. Electromagnetic nanomaterials can induce immunogenic cell death and are used in combination with cancer immunotherapy for reprogramming the tumor microenvironment.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2021)

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Metal-Phenolic Network-Enabled Lactic Acid Consumption Reverses Immunosuppressive Tumor Microenvironment for Sonodynamic Therapy

Zhan Zhang et al.

Summary: The constructed nanocomplex can remodel the immunosuppressive tumor microenvironment and achieve effective inhibition of tumors through sonodynamic therapy, while alleviating tumor hypoxia and acidic environment.

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Sonodynamic therapy complements PD-L1 immune checkpoint inhibition in a murine model of pancreatic cancer

Heather Nesbitt et al.

Summary: The study demonstrates that sonodynamic therapy (SDT) combined with anti-PD-L1 immune checkpoint inhibitor (ICI) treatment significantly reduces tumor volume and promotes increased infiltration of CD4+ and CD8+ T lymphocytes in off-target tumors in a pancreatic cancer model.

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Review Chemistry, Multidisciplinary

Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy

Thanh Chung Pham et al.

Summary: This review presents a robust strategy for designing photosensitizers for different species, highlighting the importance of organic PSs in photodynamic therapy. While previous studies have focused on nanomaterials and traditional PSs, this review sets out to report recent innovative strategies for developing organic photosensitizers for enhanced PDT, providing detailed examples to offer intuitive and specific insights to readers.

CHEMICAL REVIEWS (2021)

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Review Chemistry, Inorganic & Nuclear

Advances and perspectives in organic sonosensitizers for sonodynamic therapy

Xuejian Xing et al.

Summary: Sonodynamic therapy (SDT) is a promising minimally invasive approach for deep tumor treatment by combining low-intensity ultrasound (US) and a chemical sonosensitizer. Organic sonosensitizers have advantages like defined chemical structure and high ROS generation, but they often face challenges such as poor water solubility and low tumor targeting capacity. Strategies to improve these issues and combine SDT with other cancer treatments are discussed in this review.

COORDINATION CHEMISTRY REVIEWS (2021)

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Beyond conventional immune-checkpoint inhibition - novel immunotherapies for renal cell carcinoma

David A. Braun et al.

Summary: The management of advanced-stage renal cell carcinoma has been transformed by the development of immune-checkpoint inhibitors (ICIs). However, most patients do not derive durable clinical benefit from these agents. Innovations in immunotherapy for RCC, including ICIs with novel targets, are now in clinical development.

NATURE REVIEWS CLINICAL ONCOLOGY (2021)

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Article Chemistry, Multidisciplinary

Solutions to the Drawbacks of Photothermal and Photodynamic Cancer Therapy

Xiangyu Deng et al.

Summary: Phototherapy, such as photothermal therapy and photodynamic therapy, has shown great potential in cancer treatment, but there are still many challenges that need to be addressed. Scientists are designing different systems to overcome the drawbacks associated with phototherapy, aiming to make it a more effective cancer treatment approach in clinical practice. This article discusses the problems and solutions in phototherapy research, providing insights for future advancements in the field.

ADVANCED SCIENCE (2021)

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Article Engineering, Biomedical

Noninvasively immunogenic sonodynamic therapy with manganese protoporphyrin liposomes against triple-negative breast cancer

Huaqing Chen et al.

Summary: Sonodynamic therapy (SDT) shows promise for tumor treatment by activating immune responses and suppressing tumor growth. A multifunctional nanosonosensitizer system (FA-MnPs) has been developed, demonstrating deep-responsive SDT and immune activation, leading to tumor growth inhibition.

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Activatable polymer nanoagonist for second near-infrared photothermal immunotherapy of cancer

Yuyan Jiang et al.

Summary: The authors present a strategy for controlled immune regulation in cancer nano-immunotherapy using a photothermally activatable semiconducting polymeric pro-agonist responsive to second near-infrared window light.

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An ultrasound-driven immune-boosting molecular machine for systemic tumor suppression

Liu Wang et al.

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Mild Magnetic Hyperthermia-Activated Innate Immunity for Liver Cancer Therapy

Jiong Pan et al.

Summary: Magnetic hyperthermia therapy using specially designed composite magnetic nanoparticles showed high efficacy in inhibiting liver cancer cell proliferation and tumor growth by controlling mild hyperthermia at 43-44 degrees Celsius. This treatment also activated natural killer cells and suppressed tumor growth by upregulating UL16-binding proteins, providing a promising approach for liver cancer treatment via induced NK-cell-related antitumor immunity.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

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Semiconducting polymer nano-PROTACs for activatable photo-immunometabolic cancer therapy

Chi Zhang et al.

Summary: Proteolysis targeting chimeras (PROTACs) offer an alternative way to modulate protein homeostasis for cancer therapy, but existing PROTACs may have uncontrollable protein degradation and off-target side effects. This study presents a semiconducting polymer nano-PROTAC (SPNpro) with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy. SPNpro can generate singlet oxygen under NIR photoirradiation to eradicate tumor cells and activate protein degradation specifically in response to a cancer biomarker, enhancing tumor immunogenicity.

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Mitochondria-targeted and ultrasound-responsive nanoparticles for oxygen and nitric oxide codelivery to reverse immunosuppression and enhance sonodynamic therapy for immune activation

Changwei Ji et al.

Summary: This study developed mitochondria-targeted nanoparticles to co-deliver oxygen and nitric oxide for enhancing sonodynamic therapy and reversing immunosuppression in the tumor microenvironment. The nanoparticles showed promising results in inhibiting tumor growth, promoting immunogenic cell death, and enhancing immune response both in vitro and in vivo. The findings provide a simple strategy to improve cancer immunotherapy by combining sonodynamic therapy with oxygen and nitric oxide delivery.

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A novel self-targeting theranostic nanoplatform for photoacoustic imaging-monitored and enhanced chemo-sonodynamic therapy

Yifan Yang et al.

Summary: Sonodynamic therapy is gaining attention for its deep tissue penetration, but sonosensitizers face challenges. The self-targeting TPGS-PEM nanoplatform achieves active drug delivery and tumor enrichment while reducing side effects. The platform shows promising potential for tumor diagnosis, prognosis, and targeted therapy under precise guidance of photoacoustic/fluorescence imaging.

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Yanan Zhang et al.

Summary: This study constructed a novel CD44 receptor-targeted oxygen-carrying nanoplatform, which increased oxygen content in tumor cells and enhanced the efficiency of sonodynamic therapy. Results showed that the nanoplatform not only promoted immunogenic cell death, but also significantly activated the immune system, exhibiting anti-tumor effects.

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