BIOMATERIALS
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2022
·
IF 15.304
Mengqing Xu,Jin Zhang,Yongli Mu,Mohamed Frahat Foda,Heyou Han
Capsaicin is a natural non-toxic small molecular organic substance, which is often used clinically to reduce inflammation and pain. Here, we report an acid-responsive CaCO 3 nanoparticle loaded with capsaicin that can specifically activate TRPV1 channels and trigger tumor calcium ion therapy. The excellent acid responsiveness of calcium carbonate enables it to precisely target the tumor sites. The released capsaicin can specifically activate TRPV1 channel, overloading the intracellular calcium ion concentration and causing cell apoptosis, which provides a new safer and cheaper treatment. We proved that the naturalness and non-toxicity of capsaicin make the CaCO 3 @CAP nanoparticles have excellent biocompatibility, which has good development prospects and clinical application potential.
研究领域:
药理学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2024
·
IF 4.2
Yuan Gao,Jun Wang,Weiwei Zhang,Fei Ge,Wanzhen Li,Feiyang Xu,Ting Cui,Xing Li,Kai Yang,Yugui Tao
Calcium overload therapy refers to the condition of intracellular Ca 2+ overload, which causes mitochondrial damage and leads to the uncontrolled release of apoptotic factors into the cytoplasm through the open mitochondrial permeability pore. Based on this, it is playing an increasingly important role in the field of oncology due to its good efficacy and small side effects. However, the regulation of calcium homeostasis by cancer cells themselves, insufficient calcium ions (Ca 2+ ) in tumor sites and low efficiency of calcium entering tumor have limited its efficacy, resulting in unsatisfactory therapeutic effect. Therefore, a novel CAP/BSA@TCP-ZIF-8 nanoparticle drug carrier system was constructed that can provide Ca 2+ from exogenous sources for pH-controlled degradation and drug release at the same time. Both in vivo and in vitro experiments have proved that the nanomaterial can activate TRPV1 channels and provide exogenous Ca 2+ to cause Ca 2+ overload and apoptosis, thus achieving anti-tumor effects.
研究领域:
肿瘤学
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纳米技术
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2023
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IF 7
Dan Wei,Mingze Zeng,Borui Su,Yusheng Zhang,Kai Wu,Ting Zhou,Chengheng Wu,Jing Sun,Hongsong Fan
As one of the physical stimulus tools to target neuromodulation-related biological entities, mild thermal stimulus has attracted increasing attention in unraveling neural differentiation processing. However, thermal stimulus for neural behavior regulation has been relatively unexplored due to the challenge in finding a good method of exerting thermal stimulus. Considering the distance-dependent temperature preservation efficiency and the native importance of a bioactive matrix, we herein put forward the design of a photothermal hydrogel by immobilizing photothermal dopamine (DA) in hyaluronic acid (HA) chains. Benefitting from the minuscule disaccharide repeat unit size (≈1 nm) of HA used for the DA grafting, and the additional adhesion capacity of the DA for recruiting cells, a uniformly close distance from heating source to cells is realized. Therefore, we successfully established a near-infrared light initiated photothermal stimulus platform, with full bioactivity and high thermal manipulation efficiency. After extensive characterization, we proved that the thermal activation, from matrix to cells, triggered TRPV1 ion channel opening and Ca2+ influx, which finally promoted neural differentiation of bone marrow mesenchymal stem cells (BMSCs). This work broadens the possibilities of polymeric photothermal materials, and is of great significance for remotely manipulating neural and other cellular machinery for stem cell therapeutics in tissue engineering.
研究领域:
组织工程
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干细胞生物学
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神经科学
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生物医学工程
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光热治疗
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
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IF 8.3
Lei Zhou,Leyuan Huang,Guanfeng He,Haixin Li,Manchun Liu,Jingwen Xu
Background Allergic rhinitis (AR) is a common IgE-mediated inflammatory disease of the nasal mucosa, involving immune–neural interactions such as mast cell activation, cytokine release, and transient receptor potential vanilloid 1 (TRPV1)-mediated neuronal sensitization. Xiao-Qing-Long-Tang (XQLT) is a classical traditional Chinese medicine used clinically for AR. However, its mechanisms, particularly in macrophage regulation and TRPV1 activity, remain not fully understood. Objective This study aimed to evaluate the therapeutic effects of XQLT in an ovalbumin (OVA)-induced AR mouse model and to investigate its molecular mechanisms focusing on immune regulation, macrophage-mediated inflammation, and TRPV1 channel activity. Methods The chemical composition of XQLT was analyzed by UPLC-Q Exactive Orbitrap-HRMS system. The therapeutic effectiveness of XQLT was assessed in an OVA-induced AR mouse model. Clinical symptoms, serum biomarkers (OVA-sIgE, interleukin-4 (IL-4), histamine), and histopathological changes were assessed. Transcriptomic analysis of nasal mucosa was performed to explore molecular pathways. The anti-inflammatory effects of XQLT were evaluated in LPS-stimulated RAW264.7 and bone marrow–derived macrophages by measuring NO, cytokine expression, and NF- κ B activation. TRPV1 involvement was examined using immunohistochemistry in AR mice model, calcium imaging in HEK293 cells overexpressing TRPV1, as well as molecular docking. Results XQLT treatment significantly reduced nasal rubbing and sneezing frequencies in AR mice, decreased serum OVA-sIgE, IL-4, and histamine levels, and ameliorated nasal and lung histopathological remodeling without observable toxicity. Transcriptomic profiling revealed that XQLT modulated DEGs associated with immune response, inflammatory signaling, olfactory transduction, and sensory perception of pain. In macrophages, XQLT suppressed LPS-induced NO production, downregulated IL-6, IL-1 β , CCL2, iNOS, and COX-2 expression, and inhibited NF- κ B nuclear translocation. Importantly, XQLT reduced TRPV1 expression in AR nasal mucosa and inhibited TRPV1-mediated calcium influx in HEK293 TRPV1-overexpressing cells. Zingiberis Rhizoma (Ganjiang) was identified as a key herb contributing to TRPV1 inhibition in XQLT, supported by molecular docking analysis. Conclusion XQLT alleviates AR symptoms and tissue remodeling through coordinated suppression of macrophage-mediated inflammation and TRPV1-dependent neurogenic pathways. These findings provide novel mechanistic insights into XQLT as a safe and promising multi-target therapy for AR.
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DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-25
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IF 16.6
Li Ting,Jiang Shuhui,Zhang Ying,Luo Jie,Li Ming,Ke Hengte,Deng Yibin,Yang Tao,Sun Xiaohui,Chen Huabing
The survival of malignant tumors is highly dependent on their intrinsic self-defense pathways such as heat shock protein (HSP) during cancer therapy. However, precisely dismantling self-defenses to amplify antitumor potency remains unexplored. Herein, we demonstrate that nanoparticle-mediated transient receptor potential vanilloid member 1 (TRPV1) channel blockade potentiates thermo-immunotherapy via suppressing heat shock factor 1 (HSF1)-mediated dual self-defense pathways. TRPV1 blockade inhibits hyperthermia-induced calcium influx and subsequent nuclear translocation of HSF1, which selectively suppresses stressfully overexpressed HSP70 for enhancing thermotherapeutic efficacy against a variety of primary, metastatic and recurrent tumor models. Particularly, the suppression of HSF1 translocation further restrains the transforming growth factor β (TGFβ) pathway to degrade the tumor stroma, which improves the infiltration of antitumor therapeutics (e.g. anti-PD-L1 antibody) and immune cells into highly fibrotic and immunosuppressive pancreatic cancers. As a result, TRPV1 blockade retrieves thermo-immunotherapy with tumor-eradicable and immune memory effects. The nanoparticle-mediated TRPV1 blockade represents as an effective approach to dismantle self-defenses for potent cancer therapy.
研究领域:
肿瘤学
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免疫疗法
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
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IF 19
Xinyue Shao,Chang Qu,Guoqiang Song,Binghao Wang,Qingyun Tao,Ran Jia,Junwei Li,Jinping Wang,Hailong An
Multidrug resistance (MDR) caused by overexpressed P-glycoprotein (P-gp) in cell membrane is the main barrier for clinical tumor chemotherapy. P-gp can pump the chemical drugs out of tumor cells depending on ATP-provided energy. Herein, a photothermal-driven intracellular magnesium ion (Mg 2+ ) regulation strategy is proposed to reverse drug resistance through constructing Mg 2+ - and doxorubicin (DOX, as model drug)-loaded bimetallic Pd@Pt nanostructure (DPd@PtM). Although DPd@PtM can deliver Mg 2+ into tumor cells through endocytosis, large amount of Mg 2+ releases outside cells. To this end, the photothermal effect of Pd@Pt nanostructure in the second near-infrared region is expected to activate the thermosensitive transient receptor potential cation channel subfamily V member 1 (TRPV1) channel for extracellular released Mg 2+ influx. Intercellular Mg 2+ accumulation suppresses tricarboxylic acid cycle to block intracellular adenosine triphosphate (ATP) production (cutoff energy supply for P-gp) and reduce O 2 consumption (downregulate P-gp expression), then inhibiting P-gp-mediated tumor MDR. Both in vitro and in vivo results demonstrate that DPd@PtM can open TRPV1 channel to elevate Mg 2+ level and then inhibit the P-gp activity to enhance intracellular DOX concentration for chemotherapy. It is believed that this photothermal-mediated tumor Mg 2+ regulation therapy based on reversing MDR is a promising strategy to kill cancer cells.
研究领域:
纳米技术
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癌症研究
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生物医学工程
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药物科学
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Jie Sheng,Ziyue Zu,Jianchen Qi,Yugang Zhang,Haoguang Wu,Zhicheng Wang,Yu Miao,Tao Zheng,Sheng Wang,Linlin Zhang,Guangming Lu,Longjiang Zhang
Atherosclerosis (AS), characterized by endothelial injury, progressive inflammation, and lipid deposition, can cause adverse cardiovascular events. However, effectively addressing all these pathological conditions simultaneously is challenging. To devise a comprehensive treatment strategy for AS, we developed a nanoparticle-based mild photothermal therapy (PTT) approach, which controlled the temperature within the range of 42–45 ℃, creating a unique 'hot spring' effect. The nanoparticles used in this therapy consist of a core made of zeolitic imidazolate framework-8 (ZIF-8) nanoparticles loaded with indocyanine green (IR820), and an outer shell made of L-arginine (LA)-modified polydopamine (PDA), which is further modified with hyaluronic acid (HA) to target plaques. In vitro studies have demonstrated that mild PTT can open the TRPV1 channel in foam cells and regulate lipid metabolic diseases by maintaining a controlled temperature range of 42–45 ℃. Furthermore, the LA-PDA shell has anti-inflammatory properties, decreasing NLRP3 expression. Moreover, the eNOS/NO pathway was activated by LA, promoting the healing of injured endothelial cells (ECs). Additionally, the increased temperature enhances HSP90 expression, thereby helping to maintain eNOS. In vivo studies further confirmed that the HLPIZ-guided ‘hot spring’ effect has impressive anti-atherosclerotic capability by scavenging lipids, reducing inflammation, and repairing injured ECs simultaneously. In conclusion, our study confirmed that HLPIZ-guided mild PTT can exhibit a ‘hot spring’ effect, effectively regulating three key pathophysiological processes of AS, being a novel, potentially effective strategy for anti-AS therapy.
研究领域:
心血管疾病
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纳米技术
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治疗策略
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炎症
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脂质代谢
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 5
·748-756
·
IF 7.571
Shuangling Wang,Jie Lv,Yu Pang,Shuyang Hu,Yulong Lin,Meng Li
Despite significant achievement in chemotherapy, the off-target actions and low pharmaceutical selectivity of the therapeutic agents still limit their clinical efficacy. Herein, a multifunctional nanoplatform which integrates chemotherapy, chemodynamic therapy (CDT) and photoactivation of TRPV1 channels has been successfully established for specific cancer therapy. Polydopamine (PDA) coated hollow prussian blue nanocages (hPBNCs) are used as the photothermal switches and drug carriers for loading chemotherapeutic drug, doxorubicin (Dox). Conjugating with the TRPV1 antibodies enables the nanoplatform to bind specifically to TRPV1 channels on the plasma membrane of the TRPV1-positive cancer cells and then activate them by local heating upon NIR irradiation, leading to the over-influx of Ca2+. Critically, the laser irradiation can be carefully controlled to not only open the TRPV1 channels but also avoid burning of tumors by hyperthermia. Moreover, the exposed hPBNCs in the acidic tumor cells can decompose endogenous H2O2 into ˙OH by Fenton reaction to realize CDT, which further aggravates cancer cell apoptosis. Together with the chemotherapy caused by Dox, our nanoplatform displays an enhanced anticancer effect both in vitro and in vivo. Our work provides a powerful means for site-specific cancer synergetic therapy with high spatial and temporal resolution.
研究领域:
癌症研究
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纳米技术
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光热治疗
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）