Sonodynamic Nano-LYTACs Reverse Tumor Immunosuppressive Microenvironment for Cancer Immunotherapy DOI

Mengke Xu,

Yuxuan Hu, Jiayan Wu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 7, 2024

Extracellular and transmembrane proteins, which account for the products of approximately 40% all protein-encoding genes in tumors, play a crucial role shaping tumor immunosuppressive microenvironment (TIME). While protein degradation therapy has been applied to membrane proteins cancer cells, it rarely extended immune cells. We herein report polymeric nanolysosome targeting chimera (nano-LYTAC) that undergoes on M2 macrophages generates sonodynamic effect combinational immunotherapy. Nano-LYTAC is found have higher efficacy interleukin 4 receptor (IL-4R) compared traditional inhibitors. More importantly, revealed nano-LYTAC function macrophage concentration-dependent: downregulating CD206 expression 10 (IL-10) secretion from at low concentration, while triggering their apoptosis high concentration. Moreover, possess long retention (>48 h), allowing multiple treatments with single dose. Such synergistic immunotherapy mediated by effectively reprograms TIME via inhibiting functions regulatory T cells (Tregs), as well promoting maturation dendritic (DCs) infiltration effector (Teffs), completely suppressing growth, pulmonary metastasis, preventing recurrence under preclinical animal models.

Language: Английский

Carrier‐Free Self‐Assembly Nano‐Sonosensitizers for Sonodynamic‐Amplified Cuproptosis‐Ferroptosis in Glioblastoma Therapy DOI Creative Commons
Yang Zhu,

Xuegang Niu,

Chengyu Ding

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: April 6, 2024

Abstract Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with short blood half‐life, face challenges in transporting enough amounts ions into tumor cells. This work describes construction carrier‐free nanoparticles (Ce6@Cu NPs), which self‐assembled by coordination 2+ sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic‐triggered combination cuproptosis and ferroptosis. Ce6@Cu NPs internalized U87MG cells induce sonodynamic effect glutathione (GSH) depletion capability, promoting lipid peroxidation eventually inducing Furthermore, + concentration increases as reacts reductive GSH, resulting downregulation ferredoxin‐1 lipoyl synthase. induces oligomerization lipoylated dihydrolipoamide S‐acetyltransferase, causing proteotoxic stress irreversible cuproptosis. possess satisfactory ability to penetrate blood‐brain barrier, significant accumulation orthotopic U87MG‐Luc glioblastoma. The ferroptosis evidenced both vitro vivo minimal side effects. represents promising therapeutic strategy combining cuproptosis, potentially inspiring further research developing logical effective cancer therapies based

Language: Английский

Citations

48
Ultrasound-Based Micro-/Nanosystems for Biomedical Applications DOI
Hui Huang,

Yi Zheng,

Meiqi Chang

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(13), P. 8307 - 8472

Published: June 26, 2024

Due to the intrinsic non-invasive nature, cost-effectiveness, high safety, and real-time capabilities, besides diagnostic imaging, ultrasound as a typical mechanical wave has been extensively developed physical tool for versatile biomedical applications. Especially, prosperity of nanotechnology nanomedicine invigorates landscape ultrasound-based medicine. The unprecedented surge in research enthusiasm dedicated efforts have led mass multifunctional micro-/nanosystems being applied biomedicine, facilitating precise diagnosis, effective treatment, personalized theranostics. deployment applications is rooted profound understanding relationship among composition, structure, property, bioactivity, application, performance. In this comprehensive review, we elaborate on general principles regarding design, synthesis, functionalization, optimization abundant particular, recent advancements imaging are meticulously summarized. Furthermore, systematically elucidate state-of-the-art studies concerning progress therapeutic targeting various pathological abnormalities including cancer, bacterial infection, brain diseases, cardiovascular metabolic diseases. Finally, conclude provide an outlook field with in-depth discussion challenges faced future developments further extensive clinical translation application.

Language: Английский

Citations

47
H2O2 Photosynthesis from H2O and O2 under Weak Light by Carbon Nitrides with the Piezoelectric Effect DOI
Jin Ma, Peng Cheng,

Xiaoxiao Peng

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(30), P. 21147 - 21159

Published: July 16, 2024

Driven by the essential need of a green, safe, and low-cost approach to producing H

Language: Английский

Citations

28
Exosome‐Inhibiting Polymeric Sonosensitizer for Tumor‐Specific Sonodynamic Immunotherapy DOI
Jiayan Wu, Jingsheng Huang, Jie Yu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(25)

Published: March 6, 2024

Combination cancer immunotherapy based on electromagnetic energy and shows potent anti-cancer efficacy. However, as a factor that mediates tumor metastasis immune suppression, the impact of exosomes therapy under stimulation remains unclear. Herein, findings indicate sonodynamic (SDT) increases serum exosome levels by inducing apoptotic loosening extracellular matrix, promoting lung metastasis. To address this problem, an exosome-inhibiting polymeric sonosensitizer (EIPS) selectively inhibiting generation in response to biomarker is synthesized. EIPS consists semiconducting polymer backbone capable SDT poly(ethylene glycol) layer conjugated with tumor-specific enzyme-responsive inhibitor prodrug. After being cleaved Cathepsin B, releases active inhibitors, preventing exosome-mediated suppression As result, elicits robust antitumor effects through synergistic effect inhibition, completely establishing long-term memory effect. This first example showing combining inhibition can elicit without help typical agonists.

Language: Английский

Citations

26
Advanced Polymeric Nanoparticles for Cancer Immunotherapy: Materials Engineering, Immunotherapeutic Mechanism and Clinical Translation DOI Open Access

Wencong Jia,

Ye Wu, Yujie Xie

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Cancer immunotherapy, which leverages immune system components to treat malignancies, has emerged as a cornerstone of contemporary therapeutic strategies. Yet, critical concerns about the efficacy and safety cancer immunotherapies remain formidable. Nanotechnology, especially polymeric nanoparticles (PNPs), offers unparalleled flexibility in manipulation‐from chemical composition physical properties precision control nanoassemblies. PNPs provide an optimal platform amplify potency minimize systematic toxicity broad spectrum immunotherapeutic modalities. In this comprehensive review, basics polymer chemistry, state‐of‐the‐art designs from physicochemical standpoint for encompassing vaccines, situ vaccination, adoptive T‐cell therapies, tumor‐infiltrating cell‐targeted antibodies, cytokine therapies are delineated. Each immunotherapy necessitates distinctively tailored design strategies nanoplatforms. The extensive applications PNPs, investigation their mechanisms action enhanced particularly focused on. profiles clinical research progress discussed. Additionally, forthcoming developments emergent trends nano‐immunotherapeutics poised transform treatment paradigms into clinics explored.

Language: Английский

Citations

6
Leveraging Semiconducting Polymer Nanoparticles for Combination Cancer Immunotherapy DOI
Jiayan Wu, Kanyi Pu

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(1)

Published: Oct. 21, 2023

Abstract Cancer immunotherapy has become a promising method for cancer treatment, bringing hope to advanced patients. However, immune‐related adverse events caused by also bring heavy burden Semiconducting polymer nanoparticles (SPNs) as an emerging nanomaterial with high biocompatibility, can eliminate tumors and induce tumor immunogenic cell death through different therapeutic modalities, including photothermal therapy, photodynamic sonodynamic therapy. In addition, SPNs work functional nanocarrier synergize variety of immunomodulators amplify anti‐tumor immune responses. this review, SPNs‐based combination is comprehensively summarized according the SPNs’ modalities type loaded immunomodulators. The in‐depth understanding existing will hopefully inspire design more novel nanomaterials potent effects, ultimately promote their clinical translation.

Language: Английский

Citations

44
Structure Engineered High Piezo‐Photoelectronic Performance for Boosted Sono‐Photodynamic Therapy DOI
Rui Zhang, Dan Yang,

Pengyu Zang

et al.

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

Published: Nov. 7, 2023

Sono-photodynamic therapy is hindered by the limited tissue penetration depth of external light source and quick recombination electron-hole owing to random movement charge carriers. In this study, orthorhombic ZnSnO

Language: Английский

Citations

24
Bioorthogonal/Ultrasound Activated Oncolytic Pyroptosis Amplifies In Situ Tumor Vaccination for Boosting Antitumor Immunity DOI
Xiaoyu Xu,

Jinling Zheng,

Na Liang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(13), P. 9413 - 9430

Published: March 24, 2024

Personalized in situ tumor vaccination is a promising immunotherapeutic modality. Currently, seeking immunogenic cell death (ICD) to generate vaccines still mired by insufficient immunogenicity and an entrenched immunosuppressive microenvironment (TME). Herein, series of tetrazine-functionalized ruthenium(II) sonosensitizers have been designed screened for establishing bioorthogonal-activated vaccine via oncolytic pyroptosis induction. Based on nanodelivery-augmented bioorthogonal metabolic glycoengineering, the original selectively remolded introduce artificial target bicycle [6.1.0] nonyne (BCN) into membrane. Through specific ligation with intratumoral BCN receptors, can realize precise membrane-anchoring synchronous click-activation desired sites. Upon ultrasound (US) irradiation, activated intensively disrupt membrane dual type I/II reactive oxygen species (ROS) generation high-efficiency sonodynamic therapy (SDT). More importantly, severe damage eminently evoke maximize reverse TME, ultimately eliciting powerful durable systemic antitumor immunity. The US-triggered certified effectively inhibit growths primary distant tumors, suppress metastasis recurrence "cold" models. This bioorthogonal-driven tumor-specific induction strategy has great potential development robust vaccines.

Language: Английский

Citations

17
Membrane-anchoring clickable Iridium(III) nanosonosensitizer in situ evokes PANoptosis for augmented tumor sono-immunotherapy DOI
Xiaoyu Xu,

Shayibai Shabiti,

Xu Zhang

et al.

Nano Today, Journal Year: 2024, Volume and Issue: 56, P. 102270 - 102270

Published: April 15, 2024

Language: Английский

Citations

15
A GSH‐Responsive Prodrug with Simultaneous Triple‐Activation Capacity for Photodynamic/Sonodynamic Combination Therapy with Inhibited Skin Phototoxicity DOI

Caiting Deng,

Jingjing Zhang,

Fanchun Hu

et al.

Small, Journal Year: 2024, Volume and Issue: unknown

Published: June 5, 2024

Abstract Herein, a dual‐sensitizer prodrug, named pro‐THPC, has been designed to function as both photosensitizer and sonosensitizer prodrug for precise antitumor combination therapy with minimized skin phototoxicity. Pro‐THPC could be activated by glutathione (GSH) release the dual‐sensitizer, THPC, which simultaneously switches on fluorescence emission combined capabilities of photodynamic (PDT) sonodynamic (SDT). is further formulated into nanoparticles (NPs) water dispersity enable in vivo applications. In imaging shows that pro‐THPC NPs group exhibits significantly higher tumor‐to‐normal tissue ratio ( T / N ) = 5.2 ± 0.55) compared “always on” THPC 2.9 0.47) co‐administrated GSH synthesis inhibitor (buthionine sulfoximine, BSO) 3.2 0.63). addition, generation dual‐sensitizer's reactive oxygen species (ROS) effectively confined within tumor tissues due relatively strong correlation between ROS emission. studies demonstrate remarkable efficacy eradicate tumors through PDT SDT while reducing

Language: Английский

Citations

15