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Bioactive Materials · 2022 · IF 16.874

Black TiO2 nanoprobe-mediated mild phototherapy reduces intracellular lipid levels in atherosclerotic foam cells via cholesterol regulation pathways instead of apoptosis

Ting Dai,Wenming He,Shuangshuang Tu,Jinru Han,Bo Yuan,Chenyang Yao,Wenzhi Ren,Aiguo Wu

Given that apoptosis increases the risk of plaque rupture, strategies that reduce intracellular lipid levels without killing foam cells are warranted for safe and effective treatment of atherosclerosis. In this study, a mild phototherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow photothermal therapy (PTT) and/or photodynamic therapy (PDT) were prepared by loading hyaluronan and porphine onto black TiO 2 nanoparticles. The results showed that when temperatures below 45 °C, PTT alone and PTT + PDT significantly reduced the intracellular lipid burden without inducing evidently apoptosis or necrosis. In contrast, the use of PDT alone resulted in only a slight reduction in lipid levels and induced massive apoptosis or necrosis. The protective effect against apoptosis or necrosis after mild-temperature PTT and PTT + PDT was correlated with the upregulation of heat shock protein 27. Further, mild-temperature PTT and PTT + PDT attenuated intracellular cholesterol biosynthesis and excess cholesterol uptake via the SREBP2/LDLR pathway, and also triggered ABCA1-mediated cholesterol efflux, ultimately inhibiting lipid accumulation in foam cells. Our results offer new insights into the mechanism of lipid regulation in foam cells and indicate that the black TiO 2 nanoprobes could allow safer and more effective phototherapy of atherosclerosis.

CAS / MDL: 65-85-0 5471-63-6
研究领域: 纳米技术 · 光疗 · 心血管疾病 · 脂质代谢 · 细胞生物学
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Asian Journal of Pharmaceutical Sciences · 2022 · IF 9.273

Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasis

Chengcheng Wang,Jiao Wang,Xue Pan,Shuang Yu,Meiqi Chen,Yan Gao,Zilin Song,Haiyang Hu,Xiuli Zhao,Dawei Chen,Fei Han,Mingxi Qiao

As a non-apoptotic cell death form, ferroptosis offers an alternative approach to overcome cancer chemotherapy resistance. However, accumulating evidence indicates cancer cells can develop ferroptosis resistance by evolving antioxidative defense mechanisms. To address this issue, we prepared a Buthionine-(S,R)-sulfoximine (BSO) loaded metal organic framework (MOF) of BSO-MOF-HA (BMH) with the combination effect of boosting oxidative damage and inhibiting antioxidative defense. MOF nanoparticle was constructed by the photosensitizer of [4,4,4,4-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid)] (TCPP) and the metal ion of Zr6, which was further decorated with hyaluronic acid (HA) in order to impart active targeting to CD44 receptors overexpressed cancer cells. BMH exhibited a negative charge and spherical shape with average particle size about 162.5 nm. BMH was found to restore the susceptibility of 4T1 cells to ferroptosis under irradiation. This was attributed to the combination of photodynamic therapy (PDT) and γ-glutamylcysteine synthetase inhibitor of BSO, shifting the redox balance to oxidative stress. Enhanced ferroptosis also induced the release of damage associated molecular patterns (DAMPs) to maturate dendritic cells and activated T lymphocytes, leading to superior anti-tumor performance in vivo . Taken together, our findings demonstrated that boosting oxidative damage with photosensitizer serves as an effective strategy to reverse ferroptosis resistance.

研究领域: 癌症生物学 · 纳米医学 · 药学 · 细胞生物化学
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Advanced Therapeutics · 2022 ·Vol. 5 ·期 12 ·2200108 · IF 5.003

Oxygen-Generated Hierarchical-Structured AuNRs@MnO2@SiO2 Nanocarrier for Enhanced NIR- and H2O2-Responsive Mild-Hyperthermia Photodynamic/Photothermal Combined Tumor Therapy

Wen-Jie Zheng,Ze-Lei Zhou,Qi-Yan Lv,Xiaojie Song,Wen-Xing Zhang,Hui-Fang Cui

Tumor hypoxia greatly restricts photodynamic therapy (PDT) efficiency. Photothermal therapy (PTT) implemented at high temperatures induces local skin burning and surrounding tissue damage. Herein, an near-infrared (NIR)- and H 2 O 2 -double responsive heat- and O 2 -generating core–shell–shell AuNRs@MnO 2 @SiO 2 nanocarrier with Au nanorods (AuNRs) as core and MnO 2 as sandwiched nanolayer is developed to realize enhanced photodynamic/photothermal combined tumor therapy at mild-hyperthermia temperatures. Coating poly- l -lysine on AuNRs is capable of preventing AuNRs from aggregation and facilitating the on-site growth of MnO 2 . The mesoporous SiO 2 nanoshell provides large loading sites for payload indocyanine green (ICG). The MnO 2 nanolayer greatly enhances the singlet oxygen ( 1 O 2 ) generation efficiency of ICG both in testing tubes and in cancer cells. Consequently, the O 2 -enhanced PDT endows the AuNRs@MnO 2 @SiO 2 -ICG nanoparticles (NPs) dramatically stronger antitumor effect both in vitro and in vivo. Their tumor growth inhibition ratio (67.6%) is significantly higher than that of AuNRs@SiO 2 -ICG (28.5%) after one dose intratumor injection and NIR irradiation. Together with their good biosafety, the AuNRs@MnO 2 @SiO 2 -ICG is promisingly translational. The multifunctionality should provide the AuNRs@MnO 2 @SiO 2 NPs a nanocarrier platform for various therapeutic agents to modulate the tumor microenvironment and enhance tumor therapy efficiency.

CAS / MDL: 57-09-0
研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 材料科学 · 药学
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DALTON TRANSACTIONS · 2023 ·Vol. 52 ·期 6 ·1595-1601 · IF 4

Self-assembled nanoparticles based on cationic mono-/AIE tetra-nuclear Ir(III) complexes: long wavelength absorption/near-infrared emission photosensitizers for photodynamic therapy

Ziwei Wang,Lijuan Li,Weijin Wang,Runlin Wang,Guangzhe Li,Hang Bian,Dongxia Zhu,Martin R. Bryce

Cyclometalated Ir(III) complexes as photosensitizers (PSs) have attracted widespread attention because of their good photostability and efficient 1O2 production ability. However, their strong absorption in the UV-vis region severely limits their applications in photodynamic therapy (PDT) because the short wavelength illuminating light can be easily absorbed by the skin and subcutaneous adipose tissue causing damage to the patient's normal tissue. Herein, mono- and tetra-nuclear Ir(III) complex-porphyrin conjugates are rationally designed and synthesized, especially [TPP-4Ir]4+ exhibits obvious aggregation-induced emission (AIE) characteristics. PSs comprising Ir(III) complex-porphyrin conjugates self-assembled as nanoparticles (NPs) are successfully achieved. The obtained [TPP-Ir]+ NPs and [TPP-4Ir]4+ NPs exhibit long wavelength absorption (500–700 nm) and near-infrared emission (635–750 nm), successfully overcoming the inherent defects of short wavelength absorption of traditional Ir(III) complexes. Moreover, [TPP-4Ir]4+ NPs exhibit good biocompatibility, high 1O2 generation ability, low half-maximal inhibitory concentration (IC50) (0.47 × 10−6 M), potent cytotoxicity toward cancer cells and superior cellular uptake under white light irradiation. This work extends the scope for transition metal complex PSs with promising clinical applications.

CAS / MDL: 298-93-1
研究领域: 材料科学 · 纳米技术 · 光动力疗法 · 癌症研究 · 光化学
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Journal of Materials Chemistry B · 2023 ·Vol. 11 ·期 13 ·2937-2945 · IF 7

Calcium-peroxide-mediated cascades of oxygen production and glutathione consumption induced efficient photodynamic and photothermal synergistic therapy

Lanfang Zhang,Hui Lu,Yu Tang,Xiaojie Lu,Zhendong Zhang,Yan Zhang,Ying Liu,Chenhui Wang

Photodynamic therapy (PDT) and photothermal therapy (PTT) are potent approaches to cancer treatment. However, the tumor microenvironment (TME) characterized by severe hypoxia and abundant glutathione (GSH) significantly reduces the effectiveness of PDT. In this study, we developed an oxidative stress amplifier CaO2/ICG@ZIF-8, which was capable of self-sufficient O2 delivery and GSH depletion to enhance PDT and PTT synergistic therapy. We utilized ZIF-8 as nanocarriers that when loaded with CaO2 and indocyanine green (ICG) form CaO2/ICG@ZIF-8 nanoparticles, which exhibit a uniform particle size distribution and a hydrated particle size of about 215 nm. CaO2 reacts with water under acidic conditions to produce O2 so CaO2/ICG@ZIF-8 has an excellent O2 supply capacity, which is essential for PDT. Moreover, CaO2/ICG@ZIF-8 also reacts with GSH to form glutathione disulfides (GSSH), enhancing the therapeutic outcome of PDT by preventing the consumption of local ractive oxygen species. Beyond that, CaO2/ICG@ZIF-8 can produce strong hyperthermia with a photothermal conversion efficiency of about 44%, which is exceedingly appropriate for PTT. Owing to its augmentation, PTT/PDT mediated by CaO2/ICG@ZIF-8 demonstrates intense tumor inhibitory effects in both in vitro and in vivo studies. Notably, the Zn and Ca generated by CaO2/ICG@ZIF-8 degradation are essential elements for the body, so CaO2/ICG@ZIF-8 shows favorable safety. Altogether, the research provides a promising PDT/PTT synergistic therapeutic strategy for cancer and may show more medical applications in the future.

研究领域: 癌症治疗 · 纳米技术 · 生物医学工程 · 药学 · 材料科学
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Small · 2023 ·Vol. 19 ·期 22 ·2205511 · IF 13.3

RhRu Alloy-Anchored MXene Nanozyme for Synergistic Osteosarcoma Therapy

Yanling Liang,Chuanan Liao,Xinqi Guo,Guanhua Li,Xin Yang,Jing Yu,Jingping Zhong,Ying Xie,Li Zheng,Jinmin Zhao

Noble metal nanozymes hold promise in cancer therapy due to adjustable enzyme-like activities, unique physicochemical properties, etc. But catalytic activities of monometallic nanozyme are confined. In this study, 2D titanium carbide (Ti 3 C 2 T x )-supported RhRu alloy nanoclusters (RhRu/Ti 3 C 2 T x ) are prepared by a hydrothermal method and utilized for synergistic therapy of chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) on osteosarcoma. The nanoclusters are small in size (3.6 nm), uniform in distribution, and have excellent catalase (CAT) and peroxidase (POD)-like activities. Density functional theory calculations show that there is a significant electron transfer interaction between RhRu and Ti 3 C 2 T x , which has strong adsorption to H 2 O 2 and is beneficial to enhance the enzyme-like activity. Furthermore, RhRu/Ti 3 C 2 T x nanozyme acts as both PTT agent for converting light into heat, and photosensitizer for catalyzing O 2 to 1 O 2 . With the NIR-reinforced POD- and CAT-like activity, excellent photothermal and photodynamic performance, the synergistic CDT/PDT/PTT effect of RhRu/Ti 3 C 2 T x on osteosarcoma is verified by in vitro and in vivo experiments. This study is expected to provide a new research direction for the treatment of osteosarcoma and other tumors.

CAS / MDL: 54827-17-7
研究领域: 癌症治疗 · 纳米技术 · 材料科学 · 生物医学工程
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Journal of Materials Chemistry B · 2023 · IF 7

Protein-coated cobalt oxide-hydroxide nanospheres deliver photosensitizer IR780 iodide for near-infrared light-triggered photodynamic/photothermal/chemodynamic therapy against colon cancer

Han Hu,Shijie Yao,Qi Xu,Xing Cai,Zhimin Mo,Zhe Yang,Wen-Qiu Chen,Qianyuan He,Xiaofang Dai,Zushun Xu

Phototherapy has garnered worldwide attention for its minimal invasiveness, controllability, and spatial selectivity in treating cancer. One promising approach involves the use of near-infrared dye IR780, which demonstrates both photodynamic therapy (PDT) and photothermal therapy (PTT) effects under 808 nm laser irradiation. However, this hydrophobic dye's toxicity and limited tumor targeting severely hamper its suitability for cancer applications. Herein, a biocompatible nanoplatform CoOOH-IR780@BSA (CoIRB) has been developed to efficiently deliver IR780 and provide multi-mode treatments for colon tumors. Due to the nanocarrier coating, CoIRB nanoparticles demonstrated reliable dispersion and stability, and their biotoxicity was substantially reduced for safer blood circulation, which overcame the biological barrier of IR780. The nanoplatform has also shown considerable results in phototherapy in vivo and in vitro experiments, with successful inhibition of MC38 tumor growth through intravenous administration. Additionally, the introduction of cobalt ions could induce Fenton-like reactions to activate the production of toxic hydroxyl radicals (·OH), exerting an assistive chemodynamic therapy (CDT) effect. Notably, these nanodrugs also exhibited potential as scavengers of reductive glutathione (GSH) and hydrogen sulfide (H2S) leading to amplifying oxidative damage of reactive oxygen species (ROS). Overall, the versatile therapeutic platform, CoIRB, has opened up considerable prospects as a biotherapeutic option for combining PDT/PTT/CDT against colon cancer.

研究领域: 纳米技术 · 癌症治疗 · 光疗 · 生物医学工程
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ACS Applied Bio Materials · 2023 · IF 4.7

Physical Dissolution Combined with Photodynamic Depletion: A Two-Pronged Nanoapproach for Deoxygenation-Driven and Hypoxia-Activated Prodrug Therapy

Jingsong Lu,Jing Yu,Wensheng Xie,Xiaohan Gao,Zhenhu Guo,Zeping Jin,Ying Li,Abdul Fahad,Neema Ufurahi Pambe,Shenglei Che,Yen Wei,Lingyun Zhao

Hypoxia may enhance the chemoresistance of cancer cells and can significantly compromise the effectiveness of chemotherapy. Many efforts have been made to relieve or reverse hypoxia by introducing more oxygen into the tumor microenvironment (TME). Acting in a diametrically opposite way, in the current study, a novel nanocarrier was designed to further exhaust the oxygen level of the hypoxic TME. By creating such an oxygen depleted TME, the hypoxia-selective cytotoxin can work effectively, and oxygen exhaustion triggered chemotherapy can be achieved. Herein, deoxygenation agent, FDA-approved perfluorocarbon (PFC) and photosensitizer indocyanine green (ICG) for oxygen depletion, along with the hypoxia-activating drug tirapazamine (TPZ), were coincorporated within the poly(lactic-co-glycolic acid) (PLGA) nanoemulsion (ICG/TPZ@PPs) for the treatment of hypoxic tumors. Following hypoxia amplifying through physical oxygen dissolution and photodynamic depletion in tumors, hypoxic chemotherapy could be effectively activated to improve multitreatment synergy. After achieving local tumor enrichment, PFC-mediated oxygen dissolution combined with further ICG-mediated photodynamic therapy (PDT) under near-infrared (NIR) laser irradiation could induce enhanced hypoxia, which would activate the antitumor activity of codelivered TPZ to synergize cytotoxicity. Remarkably, in vivo experimental results exhibited that deoxygenated ICG/TPZ@PPs-based photothermal therapy (PTT), PDT, and hypoxia activated chemotherapy have an excellent synergistic ablation of tumors without obvious side effects, and therefore, a broad prospect of application of this nanocarrier could be expected.

研究领域: 癌症治疗 · 纳米技术 · 生物医学工程 · 药学
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Asian Journal of Pharmaceutical Sciences · 2022 · IF 9.273

“NIR-triggered ROS storage” photodynamic intraocular implant for high-efficient and safe posterior capsular opacification prevention

Yanjuan Huang,Tao Zhang,Qin Wei,Zishan Zeng,Yujun Gong,Xiaoyu Xu,Meixu Chen,Chunshun Zhao

Posterior capsular opacification (PCO) is the leading cause of vision loss after cataract, mainly caused by the adhesion, proliferation and trans-differentiation of post-operative residual lens epithelial cells (LECs). Effective PCO prevention remains a huge challenge to ophthalmologists and researches for decades. Herein, we developed a “NIR-triggered ROS storage” intraocular implant (CTR-Py-PpIX) based on capsular tension ring (CTR), which is concurrently linked with photosensitizer protophorphyrin IX (PpIX) and energy storage 2-pyridone derivative (Py), to guarantee instantaneous and sustainable ROS generation for LECs killing, aiming to achieve more efficient and safer photodynamic therapy (PDT) to effectively prevent PCO. The silylated PpIX-Si and Py-Si were covalently conjugated to the plasma activated CTR surface to obtain CTR-Py-PpIX. Results demonstrated that CTR-Py-PpIX had dual functions of PDT and battery, in which PpIX could generate ROS extracellularly under irradiation, with one part directly inhibiting LECs by lipid peroxidation (LPO) induction of cell membranes. Meanwhile, the excess ROS stored in Py could be continuously released to amplify LPO levels after the irradiation was removed. Ultimately, the proliferation of LECs in capsular bag was completely inhibited under mild irradiation conditions, achieving a sustainable and controlled PDT effect for effective PCO prevention with good biocompatibility. This NIR-triggered ROS storage intraocular implant would provide a more efficient and safer approach for long-term PCO prevention.

研究领域: 眼科学 · 光动力疗法 · 生物医学工程 · 材料科学
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Exploring Linker-Group-Guided Self-Assembly of Ultrathin 2D Supramolecular Nanosheets in Water for Synergistic Cancer Phototherapy

Yanhui Guo,Lukun Li,Shuheng Huang,Han Sun,Yutong Shao,Zhiliang Li,Fengling Song

Water is ubiquitous in natural systems where it builds an essential environment supporting biological supramolecular polymers to function, transport, and exchange. However, this extreme polar environment becomes a hindrance for the superhydrophobic functional π-conjugated molecules, causing significant negative impacts on regulating their aggregation pathways, structures, and properties of the subsequently assembled nanomaterials. It especially makes the self-assembly of ultrathin two-dimensional (2D) functional nanomaterials by π-conjugated molecules a grand challenge in water, although ultrathin 2D functional nanomaterials have exhibited unique and superior properties. Herein, we demonstrate the organic solvent-free self-assembly of one-molecule-thick 2D nanosheets based on exploring how side chain modifications rule the aggregation behaviors of π-conjugated macrocycles in water. Through an in-depth understanding of the roles of linking groups for side chains on affecting the aggregation behaviors of porphyrins in water, the regulation of molecular arrangement in the aggregated state (H- or J-type aggregation) was attained. Moreover, by arranging ionic porphyrins into 2D single layers through J-aggregation, the ultrathin nanosheets (thickness ≈ 2 nm) with excellent solubility and stability were self-assembled in pure water, which demonstrated both outstanding 1O2 generation and photothermal capability. The ultrathin nanosheets were further investigated as metal- and carrier-free nanodrugs for synergetic phototherapies of cancers both in vitro and in vivo, which are highly desirable by combining the advantages and avoiding the disadvantages of the single use of PDT or PTT.

研究领域: 材料科学 · 纳米技术 · 生物医学工程 · 癌症研究 · 光化学
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Multifunctional Artificial Peroxisome Basing on Lactate Oxidase as a Self-Cascade Enhancing Active Oxygen Amplifier for Tumor Therapy

Huihui Wang,Xueping Huang,Ran Gao,Ke Li,Dandan Li,Zhuobin Xu,Zemin Ling,Chun Pan,Lizeng Gao,Hao Chen

The intricacy, diversity, and heterogeneity of cancers make research focus on developing multimodal synergistic therapy strategies. Herein, an oxygen (O2) self-feeding peroxisomal lactate oxidase (LOX)-based LOX–Ce6–Mn (LCM) was synthesized using a biomineralization approach, which was used for cascade chemodynamic therapy (CDT)/photodynamic therapy (PDT) combination therapies through dual depletion of lactate (Lac) and reactive oxygen species (ROS) generation. After endocytosis into tumor cells, the endogenous hydrogen peroxide (H2O2) can be converted to O2 by the catalase-like (CAT) activity of LCM, which can facilitate the catalytic reaction of LOX to consume more Lac and alleviate tumor hypoxia to enhance the generation of singlet oxygen (1O2) upon light irradiation. In addition, the H2O2 produced by LOX catalysis and oxidase-like (OXD) activity of LCM can be catalyzed into highly toxic hydroxyl radicals (•OH) via the Fenton-like reaction, enhancing oxidative damage to tumor cells. Both in vitro and in vivo experiments confirmed that LCM significantly promoted ROS accumulation and effectively inhibited tumor growth by inducing tumor cell autophagy under the combined effect of Lac depletion and CDT with PDT. Therefore, integrally designed LCM for reprogramming metabolism and the tumor microenvironment offers a promising multimodal strategy for tumor treatments.

CAS / MDL: 1306-38-3
研究领域: 癌症研究 · 生物医学工程 · 诊疗学 · 纳米医学 · 肿瘤学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2024 · IF 5.3

Mitochondria targeted biomimetic platform for chemo/photodynamic combination therapy against osteosarcoma

Fengtian Zhang,Jiaoting Chen,Weihong Luo,Changlong Wen,Wei Mao,Yutian Yang,Chunting Liu,Youjia Xu,Weiliang Chen,Lijuan Wen

Clinical treatment for osteosarcoma (OS) is still lacking effective means, and no significant progress in OS treatment have been made in recent years. Single chemotherapy has serious side effects and can produce drug resistance easily, resulting poor therapeutic effect. As a modern and non-invasive treatment form, photodynamic therapy (PDT) is widely used to treat diverse cancers. Chemotherapy in combination with PDT is a particularly efficient antitumor method that could overcome the defects of monotherapies. Since mitochondria is a key subcellular organelle involved in cell apoptosis regulation, targeting tumor cells mitochondria for drug delivery has become an important entry point for anti-tumor therapy. Herein, we rationally designed a core-shell structured biomimetic nanoplatform, i.e., D@SLNP@OSM-IR780, to achieve tumor homologous targeting and mitochondria targeted drug release for chemotherapy combined with PDT against OS. Upon 808 nm laser irradiation, D@SLNP@OSM-IR780 exhibited excellent photo-cytotoxicity in vitro . The excellent targeting effect of D@SLNP@OSM-IR780 in tumor tissues produced a tumor inhibition rate of 98.9% in vivo . We further indicated that synergistic chemo-photodynamic effect induced by D@SLNP@OSM-IR780 could activate mitochondria-mediated apoptosis pathway, along with host immune response and potential photothermal effect. On the whole, D@SLNP@OSM-IR780 is revealed to be a promising platform for OS targeted combination therapeutics.

CAS / MDL: 31566-31-1 8002-43-5
研究领域: 肿瘤学 · 纳米技术 · 药学 · 生物医学工程
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