Precise Photodynamic Therapy by Midkine Nanobody-Engineered Nanoparticles Remodels the Microenvironment of Pancreatic Ductal Adenocarcinoma and Potentiates the Immunotherapy

ACS Nano, Год журнала: 2024, Номер 18(5), С. 4019 - 4037

Опубликована: Янв. 22, 2024

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its resistance against chemotherapy and immunotherapy due to dense desmoplastic immunosuppressive tumor microenvironment (TME). Traditional photodynamic therapy (PDT) was also less effective PDAC owing poor selectivity, insufficient penetration, accumulation of photosensitizers in sites. Here, we designed a light-responsive novel nanoplatform targeting the TME through tumor-specific midkine nanobodies (Nbs), which could efficiently deliver semiconducting polymeric nanoparticles (NPs) locally produce abundant reactive oxygen species (ROS) precise photoimmunotherapy. The synthesized nanocomposite can not only achieve multimodal imaging tumors (fluorescence photoacoustic imaging) but lead apoptosis immunogenic cell death cells via ROS under light excitation, ultimately preventing progression remodeling with increased infiltration T lymphocytes. Combined PD-1 checkpoint blockade, targeted PDT platform showed best antitumor performance markedly extended mice survival. Conclusively, this work integrating Nbs NPs provides strategy target formidable suppression activate immunity, creating possibilities boosting efficacy combination local PDT.

Язык: Английский

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Exosome‐Inhibiting Polymeric Sonosensitizer for Tumor‐Specific Sonodynamic Immunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(25)

Опубликована: Март 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.

Язык: Английский

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In situ Thermal-Responsive Magnetic Hydrogel for Multidisciplinary Therapy of Hepatocellular Carcinoma

Nano Letters, Год журнала: 2022, Номер 22(6), С. 2251 - 2260

Опубликована: Март 7, 2022

Current surgical single modality treatments for hepatocellular carcinoma (HCC) were restricted by recurrence, blood loss, significant trauma, and poor prognostic. Although multidisciplinary strategies HCC treatment have been highly recommended the clinical guidelines, there was limited choice of materials treatments. Herein, we reported an in situ formed magnetic hydrogel with promising bioapplicable thermal-responsiveness, strong adhesion wet conditions, high hyperthermia, biocompatibility, leading to efficient including postoperative transarterial embolization therapy. In vivo results indicated that this could reduce recurrence rate. The hemostatic ability thermal-responsive further demonstrated both liver scratch model tumor resection. Computed tomography imaging suggested completely embolize arterial vessels rabbit vascular intervention operation, which serve as responsive external field body temperature treatment.

Язык: Английский

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Proposal of New Safety Limits for In Vivo Experiments of Magnetic Hyperthermia Antitumor Therapy

Cancers, Год журнала: 2022, Номер 14(13), С. 3084 - 3084

Опубликована: Июнь 23, 2022

Lately, major advances in crucial aspects of magnetic hyperthermia (MH) therapy have been made (nanoparticle synthesis, biosafety, etc.). However, there is one key point still lacking improvement: the field-frequency product (H × f = 4.85 108 Am-1s-1) proposed by Atkinson-Brezovich as a limit for MH therapies. Herein, we analyze both local and systemic physiological effects overpassing this limit.Different combinations field frequency intensity exceeding (591-920 kHz, 10.3-18 kA/m) applied 21 min to WAG/RijHsd male rats, randomly distributed groups 12 animals; half them were sacrificed after h, others 10 days later. Biochemical serum analyses performed assess general, hepatic, renal and/or pancreatic function.MH raised liver temperature 42.8 ± 0.4 °C. Although five exposure was relatively well tolerated, two highest (928 kHz) (18 kA/m), more than 50% animals died. A striking elevation markers observed h surviving animals, independently used. Ten later, almost recovered all animals. those exposed 591 kHz 16 kA/m, 700 13.7 kA/m remained altered.Exceeding up 9.59 109 Am-1s-1 seems be safe, though further research needed understand impact on conditions following MH.

Язык: Английский

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Manipulating Nanoparticle Aggregates Regulates Receptor–Ligand Binding in Macrophages

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(13), С. 5769 - 5783

Опубликована: Март 11, 2022

The receptor–ligand interactions in cells are dynamically regulated by modulation of the ligand accessibility. In this study, we utilize size-tunable magnetic nanoparticle aggregates ordered at both nanometer and atomic scales. We flexibly anchor tunable sizes over cell-adhesive RGD (Arg-Gly-Asp)-active material surface while maintaining density dispersed ligands accessible to macrophages constant. Lowering dispersity increasing aggregate size constant facilitates binding integrin receptors ligands, which promotes adhesion macrophages. high dispersity, distant manipulation lift (which increases accessibility) stimulates available under augment macrophage adhesion-mediated pro-healing polarization vitro vivo. low control drop decreases repels away from aggregates, thereby suppressing adhesion, inflammatory polarization. Here, present "accessible dispersity" as a novel fundamental parameter that regulates binding, can be reversibly manipulated decreasing Limitless tuning dimensions morphology offer further insight into regulation host cells.

Язык: Английский

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The recent progress of inorganic‐based intelligent responsive nanoplatform for tumor theranostics

View, Год журнала: 2022, Номер 3(6)

Опубликована: Авг. 22, 2022

Abstract Inorganic nanoplatform exhibits great potentials in drug delivery and responsive release attributed to its inherent physicochemical properties, good biocompatibility, surface modification, easy synthesis. In this review, the recent progresses on inorganic smart bio‐responsive nanoplatforms for tumor theranostics are summarized, which could be triggered by either endogenous microenvironment (TME) or exogenous physical hopeful achieve safe, precise, high efficacy therapy. Notably, these generally dependent intelligent multifunctional design of nanocarriers, including mesoporous silica nanoparticles (MSNs), black phosphorus (BP), Prussian blue (PB), other inorganic‐based nanoparticles. Finally, perspectives challenges future translational medicine proposed.

Язык: Английский

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Lymph node-targeting nanovaccines for cancer immunotherapy

Journal of Controlled Release, Год журнала: 2022, Номер 351, С. 102 - 122

Опубликована: Сен. 20, 2022

Язык: Английский

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Mild photothermal therapy boosts nanomedicine antitumor efficacy by disrupting DNA damage repair pathways and modulating tumor mechanics

Nano Today, Год журнала: 2023, Номер 49, С. 101767 - 101767

Опубликована: Янв. 28, 2023

Язык: Английский

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Dual Tumor Exosome Biomarker Co-recognitions Based Nanoliquid Biopsy for the Accurate Early Diagnosis of Pancreatic Cancer

ACS Nano, Год журнала: 2023, Номер 17(12), С. 11384 - 11395

Опубликована: Июнь 8, 2023

Pancreatic cancer, with extremely limited treatment options and poor prognosis, urgently needs a breakthrough in early diagnosis monitoring. Tumor exosomes (T-Exos) detection is presently one of the most clinically significant liquid biopsy approaches for non-invasive pancreatic cancer diagnosis, which, unfortunately, cannot be applied as routine diagnostic tool until number obstacles, such unsatisfactory specificity sensitivity, well labor-intensive purification analysis procedures by ultracentrifugation enzyme-linked immunosorbent assay, are overcome. Here, we report facile nanoliquid assay especially specific, ultrasensitive yet economical T-Exos dual specific biomarker antigen co-recognition capturing strategy, which enabled grafting two corresponding capture antibodies on magnetic nanoparticles gold nanoparticles, accurate target tumor exosomes. This approach exhibits excellent ultrahigh sensitivity detecting low 78 pg/mL exosome protein GPC1. Successful screening 21 samples from 22 normal control cases enhanced ensures promising monitoring stage cancer.

Язык: Английский

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Liquid metal microspheres with an eddy-thermal effect for magnetic hyperthermia-enhanced cancer embolization-immunotherapy

Science Bulletin, Год журнала: 2023, Номер 68(16), С. 1772 - 1783

Опубликована: Июль 19, 2023

Язык: Английский

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