Regulation of Mitochondrial Apoptosis via siRNA-Loaded Metallo-Alginate Hydrogels: A Localized and Synergistic Antitumor Therapy

Biomaterials, Год журнала: 2025, Номер 318, С. 123164 - 123164

Опубликована: Фев. 3, 2025

Preventing relapse after resection of a primary tumor continues to be an unmet clinical need. Development adjuvant biomaterials with the capacity kill residual cancer cells is importance. Here we developed library metallo-alginate hydrogels containing high concentrations metallic ions such as Ca2+ in combination Zn2+, Li+, or Mg2+ disrupt homeostasis mitochondria by local hyperthermia. To synergistically and suppress growth rechallenged tumors, embedded oncogene-silencing nucleic acids (mTOR siRNA) loaded into polymerc nanoparticles (NPs) composed poly (β-amino esters) hydrogels, targeting that activate multi-drug resistance pathways PI3K/AKT/mTOR. Metabolomic studies showed alterations Warburg effect, mitochondrial transport, TCA cycle, confirming cell damage. In vivo this targeted therapy mice demonstrated sex-dependent effect. Male B16F10-tumor-bearing treated synergistic restrained growth. contrast, no therapeutic effect was observed female counterparts. Our results demonstrate situ-formed NP-loaded can modulate two distinct immune signaling networks are relevant for enhancing death. On basis our findings, emerges promising strategy translation.

Язык: Английский

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Photo-responsive g-C3N4/copper molybdate nanocomposites enable laser-driven multi-modal imaging, photothermal and chemodynamic therapy for hepatocellular carcinoma treatment

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 160751 - 160751

Опубликована: Фев. 1, 2025

Язык: Английский

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Supramolecular Nanoagent as a dual-blocked thermoresistance inhibitor for effective mild-temperature photothermal therapy

Biosensors and Bioelectronics, Год журнала: 2025, Номер unknown, С. 117322 - 117322

Опубликована: Март 1, 2025

Язык: Английский

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Optimization of Thermal, Mechanical, Biodegradation, and Shape Memory Properties in 4D‐Printed PLA/PCL Blends for Spinal Cages

Polymers for Advanced Technologies, Год журнала: 2025, Номер 36(3)

Опубликована: Март 1, 2025

ABSTRACT Spinal fusion cages play a crucial role in stabilizing the spine and promoting bone growth degenerative disorders. Recent advancements biodegradable polymer‐based have introduced materials with shape memory properties, enabling minimally invasive implantation improved adaptability. This study focuses on development of 4D‐printed PLA/PCL blend spinal cages, investigating their thermal, mechanical, biodegradation, alongside surface wettability through contact angle measurements. The novelty this lies identifying optimal ratio, balancing mechanical strength, biodegradability, behavior for applications. findings highlight (80:20) as most suitable composition, offering well‐balanced combination properties. Differential scanning calorimetry (DSC) analysis revealed that 20 wt% PCL enhances toughness, flexibility, crystallinity while slightly reducing glass transition temperature. Mechanical testing showed fracture elongation at tensile stress peaking before decreasing higher concentrations due to increased ductility. Biodegradation studies confirmed an increasing degradation rate content, measurements indicated greater hydrophilicity, though trend reversed concentrations. Shape demonstrated content from 10 60 wt%, recovery decreased 76.07% 61.28%, high fixity (96.42%–99.80%) was maintained. PLA/PCL20 exhibited 74.5% effect 68.75% cage design, making it promising material

Язык: Английский

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Accurate Three-Dimensional Thermal Dosimetry and Assessment of Physiologic Response Are Essential for Optimizing Thermoradiotherapy

Cancers, Год журнала: 2022, Номер 14(7), С. 1701 - 1701

Опубликована: Март 27, 2022

Numerous randomized trials have revealed that hyperthermia (HT) + radiotherapy or chemotherapy improves local tumor control, progression free and overall survival vs. alone. Despite these successes, however, some individuals fail combination therapy; not every patient will obtain maximal benefit from HT. There are many potential reasons for failure. In this paper, we focus on how HT influences hypoxia, since hypoxia negatively response as well immune surveillance. Pre-clinically, it is established reoxygenation of tumors in to related the time temperature exposure. most pre-clinical studies, occurs only during shortly after a treatment. If were case clinically, then would be challenging take advantage induced reoxygenation. An important question, therefore, whether clinic radiobiological significance. review, discuss influence thermal history both human canine cancers treated with thermoradiotherapy. Results several clinical series show observed persists 24-48 h Further, associated treatment outcome thermoradiotherapy assessed by: (1) doubling pathologic complete (pCR) soft tissue sarcomas, (2) 14 mmHg increase pO2 locally advanced breast achieving 9 decrease did respond (3) significant correlation between extent (as by probes marker drug immunohistochemistry) duration control sarcomas. The persistence out post distinctly different reported rodent studies. series, comparison data physiologic shows within same tumor, temperatures at higher end distribution likely kill cells, resulting reduced oxygen consumption rate, while lower improve perfusion. However, does occur all subjects, leading uncertainty about thermal-physiologic relationship. This stems limited knowledge spatiotemporal characteristics response. We conclude recommendations future research emphasis retrieving co-registered before order begin unravel complex thermophysiologic interactions appear

Язык: Английский

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Tumor-Associated Macrophage Targeting of Nanomedicines in Cancer Therapy

Pharmaceutics, Год журнала: 2023, Номер 16(1), С. 61 - 61

Опубликована: Дек. 29, 2023

The tumor microenvironment (TME) is pivotal in growth and metastasis, aligning with the “Seed Soil” theory. Within TME, tumor-associated macrophages (TAMs) play a central role, profoundly influencing progression. Strategies targeting TAMs have surfaced as potential therapeutic avenues, encompassing interventions to block TAM recruitment, eliminate TAMs, reprogram M2 or bolster their phagocytic capabilities via specific pathways. Nanomaterials including inorganic materials, organic materials for small molecules large stand at forefront, presenting significant opportunities precise modulation of enhance efficacy cancer treatment. This review provides an overview progress designing nanoparticles interacting strategy therapy. comprehensive presents role TME various strategies promising frontier ever-evolving field current trends challenges associated TAM-based therapy are presented.

Язык: Английский

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Theranostic applications of peptide-based nanoformulations for growth factor defective cancers

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 260, С. 129151 - 129151

Опубликована: Янв. 4, 2024

Язык: Английский

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Immunomodulatory Prodrug Micelles Imitate Mild Heat Effects to Reshape Tumor Microenvironment for Enhanced Cancer Immunotherapy

ACS Nano, Год журнала: 2024, Номер 18(7), С. 5632 - 5646

Опубликована: Фев. 12, 2024

Physical stimulation with mild heat possesses the notable ability to induce immunomodulation within tumor microenvironment (TME). It transforms immunosuppressive TME into an immune-active state, making tumors more receptive immune checkpoint inhibitor (ICI) therapy. Transient receptor potential vanilloid 1 (TRPV1), which can be activated by heat, holds these alterations in TME. However, achieving precise temperature control while protecting neighboring tissues remains a significant challenge when using external sources. Taking inspiration from sensation elicited capsaicin-containing products activating TRPV1, this study employs capsaicin chemically stimulate imitating immunomodulatory benefits akin those induced heat. This involves developing glutathione (GSH)-responsive prodrug micelle system deliver and ICI (BMS202) concurrently. Following intravenous administration, micelles accumulate at site through enhanced permeability retention effect. Within GSH-rich TME, disintegrate release BMS202. The released activates TRPV1 expressed enhancing programmed death ligand expression on cell surfaces promoting T recruitment rendering it immunologically active. Meanwhile, liberated BMS202 blocks checkpoints cells cells, recruited ultimately eradicating tumors. innovative strategy represents comprehensive approach fine-tune significantly amplifying effectiveness of cancer immunotherapy exploiting pathway enabling situ

Язык: Английский

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Vaporization phosphorization-mediated synthesis of phosphorus-doped TiO₂ nanocomposites for combined photodynamic and photothermal therapy of renal cell carcinoma

Journal of Materials Chemistry B, Год журнала: 2024, Номер 12(16), С. 4039 - 4052

Опубликована: Янв. 1, 2024

Clear cell renal carcinoma (ccRCC) is a disease with high incidence and poor prognosis. The conventional treatment involves radiotherapy chemotherapy, but chemotherapeutic agents are often associated side effects, i.e., cytotoxicity to nontumor cells. Therefore, there an urgent need for the development of novel therapeutic strategies ccRCC. We synthesized spherical P/TiO2 nanoparticles (P/TiO2 NPs) by vaporization phosphorization (VP). X-ray photoelectron spectroscopy (XPS) ultraviolet-visible diffuse reflectance (UV-Vis DRS) analyses confirmed that anatase TiO2 surface was successfully doped phosphorus produced large number oxygen vacancies (OV). Serving as photosensitizer, NPs not only extended photoresponse range near-infrared II region (NIR II) also introduced donor energy level lower than conduction band, narrowing band gap, which could facilitate migration photogenerated charges trigger synergistic photodynamic therapy (PDT) photothermal (PTT). During NIR irradiation in vitro, generated local heat various radicals, including 1O2, ˙O2-, H2O2, ˙OH, damaged ccRCC In vivo, administration + reduced tumor volume 80%, had potential inhibit metastasis suppressing intratumor neoangiogenesis. showed superior safety efficacy relative agent used treatment. This study innovative paradigm cancer treatment, highlighting safe effective nanomaterials presenting compelling new option clinical applications anticancer therapy.

Язык: Английский

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A Review of the Current Clinical Evidence for Loco-Regional Moderate Hyperthermia in the Adjunct Management of Cancers

Cancers, Год журнала: 2023, Номер 15(2), С. 346 - 346

Опубликована: Янв. 5, 2023

Regional hyperthermia therapy (RHT) is a treatment that applies moderate heat to tumours in an attempt potentiate the effects of oncological treatments and improve responses. Although it has been used for many years, mechanisms action are not fully understood. Heterogenous practices, poor quality assurance, conflicting clinical evidence lack familiarity have hindered its use. Despite this, several centres recognise potential adopted their standard protocols. In recent times, significant technical improvements made there increasing pool could revolutionise Our narrative review aims summarise recently published prospective trial present RHT when added cancer treatments. total, 31 studies with higher-quality across various subsites discussed herein. all these level 1 evidence, benefits improving local tumour control, survival outcomes life scores were observed different minimal increase toxicities. This paper may serve as reference considering this technique specific indications.

Язык: Английский

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