Organic Sonodynamic Materials for Combination Cancer Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(51)

Published: June 1, 2023

Sonodynamic therapy (SDT) is a promising non-invasive therapeutic modality to treat deep-seated tumors owing the good tissue penetration ability and spatiotemporal controllability of ultrasound (US); however, low sonodynamic activity potential side effects greatly limit its clinical translation. Cancer immunotherapy that leverages immune system fight against cancer has great synergize with SDT for treatment high efficiency safety. In this review, convergence exert their merits break through limitations combination sono-immunotherapy are discussed. The focus on development construction organic materials immunotherapeutic efficiency. These not only induce immunogenic cell death improve tumor immunogenicity via but also activate antitumor immunity immuno-oncology drug-mediated pathway modulation. various drugs sonosensitizers categorized discussed along prospects challenges

Language: Английский

---

Oxygen‐Deficient Molybdenum Oxide Nanosensitizers for Ultrasound‐Enhanced Cancer Metalloimmunotherapy

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(9)

Published: Jan. 2, 2023

Oxygen-deficient molybdenum oxide (MoOX ) nanomaterials are prepared as novel nanosensitizers and TME-stimulants for ultrasound (US)-enhanced cancer metalloimmunotherapy. After PEGylation, MoOX -PEG exhibits efficient capability US-triggered reactive oxygen species (ROS) generation glutathione (GSH) depletion. Under US irradiation, generates a massive amount of ROS to induce cell damage immunogenic death (ICD), which can effectively suppress tumor growth. More importantly, itself further stimulates the maturation dendritic cells (DCs) triggeres activation cGAS-STING pathway enhance immunological effect. Due robust ICD induced by SDT DC stimulated -PEG, combination treatment -triggered aCTLA-4 amplifies antitumor therapy, inhibits metastases, elicits immune responses defeat abscopal tumors.

Language: Английский

---

Ultrathin Clay Nanoparticles‐Mediated Mutual Reinforcement of Ferroptosis and Cancer Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(9)

Published: Nov. 8, 2023

Ferroptosis-triggered immunogenic cell death (ICD) is widely adopted to potentiate the body's antitumor immunity by catalyzing production of toxic reactive oxygen species (ROS). However, efficacy ferroptosis and immunotherapy greatly restricted intracellular abundant glutathione (GSH) immunosuppressive tumor microenvironment (TME). Herein, a facile bottom-up method for solvent-free synthesis ultrathin manganese (Mn)-based layered double hydroxide nanosheets with high loading efficiency pro-inflammatory cytokine interferon (IFNγ) (IFNγ/uMn-LDHs) proposed mutually reinforce systemic immunity. The introduction ions significantly contributes GSH depletion hydroxyl radical generation, which can be further enhanced IFNγ delivery-induced SLC7A11 downregulation. ICD effect after cooperates intrinsic immunomodulatory property IFNγ/uMn-LDHs facilitate maturation dendritic cells (DCs) priming T cells. secretion from activated CD8

Language: Английский

---

Boosting Checkpoint Immunotherapy with Biomaterials

ACS Nano, Journal Year: 2023, Volume and Issue: 17(4), P. 3225 - 3258

Published: Feb. 6, 2023

The immune checkpoint blockade (ICB) therapy has revolutionized the field of cancer treatment, while low response rates and systemic toxicity limit its clinical outcomes. With rapid advances in nanotechnology materials science, various types biomaterials have been developed to maximize therapeutic efficacy minimizing side effects by increasing tumor antigenicity, reversing immunosuppressive microenvironment, amplifying antitumor response, reducing extratumoral distribution inhibitors as well enhancing their retention within target sites. In this review, we reviewed current design strategies for different augment ICB effectively then discussed present representative biomaterial-assisted modulation targeted delivery boost therapy. Current challenges future development prospects expanding with were also summarized. We anticipate review will be helpful developing emerging promoting application

Language: Английский

---

Augmenting Immunogenic Cell Death and Alleviating Myeloid‐Derived Suppressor Cells by Sono‐Activatable Semiconducting Polymer Nanopartners for Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(33)

Published: May 11, 2023

Inducing immunogenic cell death (ICD) by sonodynamic therapy (SDT) is promising for cancer immunotherapy, which however inefficient due to oxygen depletion that compromises SDT effect and mediates recruitment of immunosuppressive myeloid-derived suppressor cells (MDSCs). The fabrication sono-activatable semiconducting polymer nanopartners (SPNTi ) simultaneously augment ICD alleviate MDSCs immunotherapy reported. A polymer, hydrophobic hypoxia-responsive tirapazamine (TPZ)-conjugate, MDSC-targeting drug (ibrutinib) are encapsulated inside such SPNTi with surface shell a singlet (1 O2 )-cleavable amphiphilic polymer. TPZ ibrutinib serve as partners enlarge immunotherapeutic effect. Upon sono-activation, generate 1 break -cleavable polymers in situ liberations TPZ-conjugate tumor sites, consumed create severe hypoxic microenvironment, which, activated augmenting action, while alleviates promoting antitumor immunological In bilateral mouse model, -mediated results growth restraints primary distant tumors noteworthy precaution metastases. This study thus provides strategy high precision safety via overcoming post-treatment hypoxia targeting MDSCs.

Language: Английский

---

A Metal–Phenolic Nanocoordinator Launches Radiotherapeutic Cancer Pyroptosis Through an Epigenetic Mechanism

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(23)

Published: March 16, 2023

Abstract Radiotherapy, although clinically effective in immunoactivation, still cannot radio‐functionalize tumor as a potent immunogenetic center. Given that newly found pyroptosis efficiently releases immunogenic damage‐associated molecular patterns, initiating radiotherapeutic may turn vision of radiotherapy‐induced immunity into reality. However, precondition is the absent gasdermin E (GSDME), which essentiates caspase‐3‐mediated pyroptosis, can be well translated cancer cells. Here, an epigenetic strategy to launch radiotherapy introduced. The nanocoordinator (PWE) constructed via metal–phenolic coordination between polyphenolic DNA methyltransferase inhibitor (epigallocatechin‐3‐gallate, EGCG), high‐Z radiosensitizer (W 6+ ), and polyphenol‐modified block copolymer. While recovering GSDME expression by EGCG, PWE cleaves fragmented N‐terminal (pyroptotic key protein) caspase‐3. To examine anti‐tumor immune activities, amplifies immunological effects traditional decreases radiotherapy‐upregulated regulatory T cells, providing new insight radiotherapy.

Language: Английский

---

Biomaterials Facilitating Dendritic Cell‐Mediated Cancer Immunotherapy

Advanced Science, Journal Year: 2023, Volume and Issue: 10(18)

Published: April 23, 2023

Dendritic cell (DC)-based cancer immunotherapy has exhibited remarkable clinical prospects because DCs play a central role in initiating and regulating adaptive immune responses. However, the application of traditional DC-mediated is limited due to insufficient antigen delivery, inadequate presentation, high levels immunosuppression. To address these challenges, engineered biomaterials have been exploited enhance immunotherapeutic effects. In this review, vital principal components that can effects are first introduced. The parameters considered rational design biomaterials, including targeting modifications, size, shape, surface, mechanical properties, which affect biomaterial optimization DC functions, further summarized. Moreover, recent applications various field reviewed, those serve as component delivery platforms, remodel tumor microenvironment, synergistically other antitumor therapies. Overall, present review comprehensively systematically summarizes related promotion functions; specifically focuses on advances designs for activation eradicate tumors. challenges opportunities treatment strategies designed amplify via discussed with aim inspiring translation future immunotherapies.

Language: Английский

---

Ferroptosis and Necroptosis Produced Autologous Tumor Cell Lysates Co-Delivering with Combined Immnoadjuvants as Personalized In Situ Nanovaccines for Antitumor Immunity

ACS Nano, Journal Year: 2023, Volume and Issue: 17(15), P. 14475 - 14493

Published: July 19, 2023

Nanovaccine-based immunotherapy has been considered as a major pillar to stimulate the host immune system recognize and eradicate tumor cells well establish long-term memory prevent relapse metastasis. However, weak specificity low cross-presentation of antigens, immunosuppressive microenvironments tissues, are still obstacles on exerting therapeutic performance nanovaccines sufficiently. Herein, we design construct cytosine guanine dinucleotide (CpG) oligodeoxynucleotide (ODN)-loaded aluminum hydroxyphosphate nanoparticles covered by Fe-Shikonin metal-phenolic networks (MPNs) (Alum-CpG@Fe-Shikonin NPs) personalized in situ for antitumor immunity. Upon internalization cells, shell MPNs will disassemble into Fe2+ Shikonin elicit immunogenic cell death through ferroptosis necroptosis. Then, dying cell-released autologous lysates be absorbed Alum NPs codelivered with CpG ODN professional antigen-presenting temporally spatially activate multistep cascade responses, including dendritic maturation, antigen cross-presentation, natural killer cytotoxic T lymphocyte infiltrations, tumor-associated macrophage repolarization. Benefiting from synergistic effects NPs, ODN, MPNs, our Alum-CpG@Fe-Shikonin exhibit drastic cytotoxicity accurate selectivity eradicating primary tumor, strong abscopal effect inhibiting distant preventing metastasis recurrence. Because report provides feasible strategy make full use lysates, which present an entire spectrum patient's personal epitopes without complicated ex vivo processes, such extraction, purification, sequencing, it may promote development

Language: Английский

---

Activatable Semiconducting Polymer Pro‐nanomodulators for Deep‐Tissue Sono‐immunotherapy of Orthotopic Pancreatic Cancer

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(30)

Published: May 17, 2023

Immunotherapy has provided a promising modality for cancer treatment, while it often the issues of limited response rates and potential off-target side effects in clinical practice. We herein report construction semiconducting polymer pro-nanomodulators (SPpMs) with ultrasound (US)-mediated activatable pharmacological actions deep-tissue sono-immunotherapy orthotopic pancreatic cancer. Such SPpMs consist sonodynamic backbone grafted poly(ethylene glycol) chains linked two immunomodulators (a programmed death-ligand 1 blocker an indoleamine 2,3-dioxygenase inhibitor) via singlet oxygen (1 O2 )-cleavable segment. In view excellent property core, enable effective generation under US even depth up to 12 cm. The generated not only ablates tumors effect induces immunogenic cell death, but also destroys -cleavable segments allow situ release tumors. This synergetic action results boosted antitumor immune reversing tumor immunosuppressive pathways. As such, mediate completely eradicate effectively prevent metastasis. Moreover, such activation reduces possibility immune-related adverse events. study thus provides smart nanoplatform precise immunotherapy deep-seated

Language: Английский

---

A Hierarchical Structured Fiber Device Remodeling the Acidic Tumor Microenvironment for Enhanced Cancer Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(21)

Published: March 13, 2023

Abstract The acidic microenvironment of tumors significantly reduces the anti‐tumor effect immunotherapy. Herein, a hierarchically structured fiber device is developed as local drug delivery system for remodeling tumor (TME) to improve therapeutic Proton pump inhibitors in matrix can be sustainedly released inhibit efflux intracellular H + from cells, resulting TME. targeted micelles and M1 macrophage membrane‐coated nanoparticles internal cavities induce immunogenic cell death (ICD) cells phenotypic transformation tumor‐associated macrophages (TAMs), respectively. relief acidity TME further promotes ICD polarization TAMs, alleviating immunosuppressive synergistically enhancing antitumor immune response. In vivo results reveal this restores pH value 6.8 7.2 exhibit an excellent immunotherapeutic effect.

Language: Английский

---