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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-18 · IF 10.6

Bi2S3/Ti3C2-TPP nano-heterostructures induced by near-infrared for photodynamic therapy combined with photothermal therapy on hypoxic tumors

Jiang Hanwen,Sun Jingxian,Liu Fucong,Zhao Yuanjiao,Chen Xin,Dai Changsong,Wen Zhaohui

Background Photodynamic therapy (PDT) efficacy of bismuth sulfide (Bi 2 S 3 ) semiconductor has been severely restricted by its electron–hole pairs (e − −h + ) separation inefficiency and oxygen (O 2 ) deficiency in tumors, which greatly hinders reactive oxygen species (ROS) generation and further clinical application of Bi 2 S 3 nanoparticles (NPs) in biomedicine. Results Herein, novel Bi 2 S 3 /titanium carbide (Ti 3 C 2 ) two-dimensional nano-heterostructures (NHs) are designed to realize multimode PDT of synchronous O 2 self-supply and ROS generation combined with highly efficient photothermal tumor elimination for hypoxic tumor therapy. Bi 2 S 3 /Ti 3 C 2 NHs were synthesized via the in situ synthesis method starting from Ti 3 C 2 nanosheets (NSs), a classical type of MXene nanostructure. Compared to simple Bi 2 S 3 NPs, Bi 2 S 3 /Ti 3 C 2 NHs significantly extend the absorption to the near-infrared (NIR) region and enhance the photocatalytic activity owing to the improved photogenerated carrier separation, where the hole on the valence band (VB) of Bi 2 S 3 can react with water to supply O 2 for the electron on the Ti 3 C 2 NSs to generate ·O 2 − and ·OH through electron transfer. Furthermore, they also achieve 1 O 2 generation through energy transfer due to O 2 self-supply. After the modification of triphenylphosphium bromide (TPP) on Bi 2 S 3 /Ti 3 C 2 NHs, systematic in vitro and in vivo evaluations were conducted, revealing that the synergistic-therapeutic outcome of this nanoplatform enables complete eradication of the U251 tumors without recurrence by NIR laser irradiation, and it can be used for computed tomography (CT) imaging because of the strong X-ray attenuation ability. Conclusion This work expands the phototherapeutic effect of Bi 2 S 3 -based nanoplatforms, providing a new strategy for hypoxic tumor theranostics.

CAS / MDL: 7789-24-4
研究领域: 纳米技术 · 生物医学工程 · 癌症治疗 · 材料科学 · 光疗
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Biomaterials Science · 2019 ·Vol. 7 ·期 11 ·4769-4781 · IF 5.251

AgBiS2-TPP nanocomposite for mitochondrial targeting photodynamic therapy, photothermal therapy and bio-imaging under 808 nm NIR laser irradiation

Mingdi Sun,Dan Yang,Chen Wang,Huiting Bi,Yuan Zhou,Xiangxi Wang,Jiating Xu,Fei He,Shili Gai,Piaoping Yang

808 nm near-infrared (NIR) light-induced biological theranostics is gradually becoming a popular method for cancer treatment. Meanwhile, mild synthetic methods to prepare medicines and gentle treatment conditions for cancer patients are becoming increasingly important to oncotherapy. Herein, tiny AgBiS2 nanodots were synthesized via a simple method, and for the first time, discovered to produce a photodynamic therapy (PDT) effect for cancer treatment under 808 nm laser irradiation, which was characterized by both chemical probe and intracellular reactive oxygen species (ROS) detection. Subsequently, because tumor cells have more mitochondria than normal cells to generate more energy to maintain rapid growth for population expansion, and triphenylphosphonium (TPP) can transport tiny nanoparticles into the mitochondria, the as-synthesized AgBiS2 nanodots were combined with TPP in a facile route. In our design, the AgBiS2 nanodots exhibit photothermal properties and TPP can enhance the photothermal properties of the AgBiS2 nanodots to a certain extent, which make the AgBiS2-TPP nanocomposite applicable in photothermal therapy (PTT). Furthermore, the AgBiS2-TPP nanocomposite showed a remarkable computed tomography (CT) imaging performance for tumor diagnosis. The facile synthetic strategy, satisfactory anticancer effect, CT imaging and mitochondrial targeting of the AgBiS2-TPP nanocomposite demonstrate its high potential in the anticancer field.

研究领域: 肿瘤学 · 纳米医学 · 生物医学工程
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Nano Today · 2024 · IF 13.2

Development of a multi-effect CS-TPP-dsNFS1 mosquito control nanosystem that induces muscle ferroptosis through suppressing iron-sulfur-cluster biosynthesis

Shiwen Duan,Jianmin Gao,Haoqin Ke,Chengquan Huang,Chaoyue Sun,Yujie Ren,Yixue Zhang,Xiumei Jiang,Yinliang Wang,Gang Liu

Mosquitoes are notorious for transmitting arbovirus diseases. Existing genetic-based control strategies only target one of mosquitoes’ flying, blood-sucking and reproduction behaviors and are technically demanding, limiting their real-world application. Therefore, there is an imperative need to identify novel molecular targets for developing multi-effect, easy-to-deploy mosquito control strategies. We herein identified and characterized the function of mosquito iron-sulfur-cluster assembly protein AalbNFS1. Silencing AalbNFS1 with double-strand RNAs (dsNFS1) caused evident metabolic and enzyme activity abnormalities in mosquito tissues and cells. Further analyses revealed that AalbNFS1 deficiency simultaneously reduced mosquitoes’ flying, blood-sucking and reproductive abilities by inducing muscle cell ferroptosis, confirming AalbNFS1 as a multi-effect molecular target for mosquito control purposes. To facilitate the real-world deployment of dsNFS1, a chitosan-tripolyphosphate-dsNFS1 (CS-TPP-dsNFS1) nanosystem was synthesized, generating satisfactory mosquito control effects. Collectively, our study pioneers the research on iron-sulfur-cluster biosynthesis mechanisms in mosquitoes and develops an effective mosquito control nanosystem with promising real-world applicability.

CAS / MDL: 9012-76-4 7758-29-4
研究领域: 昆虫学 · 分子生物学 · 生物技术 · 公共卫生
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INORGANIC CHEMISTRY · 2024 · IF 4.3

Toward an Ideal Light Source for Indoor Photosynthesis: Broadband Red Emission in Zero-Dimensional Hafnium-Based Metal Halide (TPP)2HfCl6·4C2H3N:Sb3+

Xiangyan Yun,Yanrong Zhu,Yu Wang,Zutao Fan,Kang Zhou,Hanlin Hu,Haizhe Zhong,Henan Li,Yumeng Shi

With suitable electron–phonon coupling strength, a near-unity broadband photoluminescence quantum yield (PLQY) can be achieved in organic–inorganic hybrid metal halides (OIHMHs) via self-trapped exciton (STE) emission. However, it is still challenging to obtain high-quality red emission from OIHMHs with a desirable emission wavelength and high chemical stability, which hinders their practical application in high-performance displays, plant-growth lighting, and biomedical imaging. Herein, a series of hafnium-based zero-dimensional (TPP)2HfCl6·4C2H3N (TPP: tetraphenylphosphonium) single crystals with different Sb3+ doping levels are synthesized. The Sb3+-doped (TPP)2HfCl6·4C2H3N shows dual-band red emission with a full width at half-maximum of 178 nm and a high PLQY of 91.09%. This broad dual-band emission originates from dopant-induced extrinsic free excitons and STEs. Furthermore, (TPP)2HfCl6·4C2H3N:Sb3+ was employed as a luminescence converter in a light-emitting diode (LED) for plant growth regulation. A correlated color temperature of 4055 K and a color rendering index of 82.13 were achieved upon excitation of the LED at 365 nm. These results provide fundamental perspectives on the emission behavior of Sb3+-doped OIHMHs and illustrate their promise for use in plant-growth lighting.

研究领域: 材料科学 · 光学 · 农业科学
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Applied Catalysis O: Open · 2024 · IF 0

Platinum meso-tetraphenylporphyrin (Pt(II)TPP) mediated the efficient oxidation of alkyl aromatics to ketones in the presence of tert-butyl hydroperoxide

Ya-Song Lin,Hui-Zi Han,Xiao-Qi He,Xian-Tai Zhou

A highly efficient and selective protocol for the oxidation of alkyl aromatics with tert -butyl hydroperoxide (TBHP) oxidant over platinum meso -tetraphenylporphyrin (Pt( II )TPP) was developed. Various alkyl aromatics were selectively converted to ketones smoothly with yields higher than 90% under the optimized conditions. Kinetic studies revealed that the oxidation was first-order with respect to the substrate, and the activation energy ( E a ) was 50.8 kJ mol −1 . Moreover, a mechanism involving high-valence platinum species and free radicals was proposed.

研究领域: 有机化学 · 催化化学 · 物理化学
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DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY · 2019 · IF 2.367

Doxorubicin derivative loaded acetal-PEG-PCCL micelles for overcoming multidrug resistance in MCF-7/ADR cells

Xin-Cheng Zhong,Wen-Hong Xu,Zi-Ting Wang,Wang-Wei Guo,Jie-Jian Chen,Ning-Ning Guo,Tian-Tian Wang,Meng-Ting Lin,Zhen-Tao Zhang,Yi-Ying Lu,Qi-Yao Yang,Min Han,Dong-Hang Xu,Jian-Qing Gao

Objective: This study was aimed to develop DOX-TPP loaded acetal-PEG-PCCL micelles to improve the clinical efficacy of drug resistance tumor.Significance: Chemotherapy is one of the main treatments for breast cancer but is plagued by multidrug resistance (MDR). DOX-TPP-loaded micelles can enhance the specific concentration of drugs in the tumor and improve the efficacy and overcome MDR.Methods: In this study, DOX-TPP-loaded micelles based on acetal-PEG-PCCL were prepared and their physicochemical properties were characterized. The cellular uptake and ability to induce apoptosis of the micelles was confirmed by flow cytometry in MCF-7/ADR cells. In addition, cytotoxicity of the micelles was studied in MCF-7 cells and MCF-7/ADR cells. Confocal is used to study the subcellular distribution of DOX. Free DOX-TPP or DOX-TPP-loaded acetal-PEG-PCCL micelles were administered via intravenous injection in the tail vain for the biodistribution study in vivo.Results: The diameter of micelles was about 102.4 nm and their drug-loading efficiency is 61.8%. The structural characterization was confirmed by 1H NMR. The micelles exhibited better antitumor efficacy compared to free doxorubicin in MCF-7/ADR cells by MTT assay. The apoptotic rate and the cellular uptake of micelles were significantly higher than free DOX and DOX-TPP. Micelles can efficiently deliver mitochondria-targeting DOX-TPP to tumor cells. The result of bio-distribution showed that the micelles had stronger tumor infiltration ability than free drugs.Conclusions: In this study, mitochondriotropic DOX-TPP was conjugated to the nanocarrier acetal-PEG-PCCL via ionic interaction to form a polymer, which spontaneously formed spherical micelles. The cytotoxicity and cellular uptake of the micelles are superior to free DOX and exhibit mitochondrial targeting and passive tumor targeting, indicating that they have potential prospects.

CAS / MDL: 68-12-2 7761-88-8
研究领域: 药学 · 肿瘤学 · 纳米技术 · 药物递送系统
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Environmental Chemistry and Ecotoxicology · 2025 · IF 8.2

New Approach Methodologies (NAMs) reveal triphenyl phosphate (TPP) disrupts lipid metabolism in estuarine fish via PPARγ activation: A concentration-dependent transcriptomic and molecular docking study

Jinzhi Ren,Ying Peng,Chenyang Sun,Yining Zhang,Jianjun Li,Simin Xia,Caixia Gao,Yimeng Wang,Xiangping Nie

There is an urgent need for a more efficient and ethical approach to chemical toxicity assessment. The emergence of New Approach Methodologies (NAMs) based on fish embryos transcriptomics provides a promising alternative. Triphenyl phosphate (TPP) — a pervasive contaminant in estuaries — disrupts lipid homeostasis in mammals via PPARγ activation, yet its ecotoxicological impacts on estuarine fish remain unknown. Leveraging NAMs, this study integrates concentration-dependent transcriptomics (CDT), molecular docking, and phenotypic toxicity assays to unravel effects of TPP on embryonic development and lipid metabolism in the benthic fish Mugilogobius chulae . We found that TPP induced significant lethality (LC₅₀ = 1.86 × 10 6  ng/L) and teratogenicity (EC₅₀ = 5.27 × 10 5  ng/L), suppressing spontaneous movement, heart rate, and hatching. At concentrations of 5270 ng/L and 52,700 ng/L, TPP elevated triglycerides, total cholesterol, and hepatotoxicity markers (alanine aminotransferase / aspartate aminotransferase). CDT analysis identified fatty acid metabolism pathways as the most sensitive targets, with TPP upregulating PPARγ while downregulating CD36 and ACSL5 — indicating blocked fatty acid oxidation and explaining lipid accumulation. Crucially, co-exposure with PPARγ antagonist GW9662 reversed metabolic disorders, validating the mechanistic role of PPARγ. Furthermore, molecular docking confirmed that TPP binds PPARγ with agonist-like affinity. This work establishes a NAM-based framework for deciphering the toxicity of contaminants of emerging concern in estuarine ecosystems, offering novel tools for ecological risk assessment.

CAS / MDL: 22978-25-2
研究领域: 生态毒理学 · 环境科学 · 毒理基因组学 · 分子生物学 · 水生毒理学
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International Journal of Nanomedicine · 2023 · IF 8

Mitochondrial Calcium Nanoregulators Reverse the Macrophage Proinflammatory Phenotype Through Restoring Mitochondrial Calcium Homeostasis for the Treatment of Osteoarthritis

Xiao Lei,Guodong Tan,Yiming Wang,Li Chen,Yuan Cao,Bingxin Si,Zhen Zhen,Bei Li,Yan Jin,Wei Wang,Fang Jin

Introduction Osteoarthritis (OA) is a chronic degenerative joint disease accompanied by an elevated macrophage proinflammatory phenotype, which is triggered by persistent pathologically elevated calcium ion levels in mitochondria. However, existing pharmacological compounds targeting the inhibition of mitochondrial calcium ion (m[Ca2+]) influx are currently limited in terms of plasma membrane permeability and low specificity for ion channels and transporters. In the present study, we synthesized mesoporous silica nanoparticle-amidated (MSN)-ethylenebis (oxyethylenenitrilo)tetraacetic acid (EGTA)/triphenylphosphine (TPP)-polyethylene glycol (PEG) [METP] nanoparticles (NPs), which specifically target mitochondria and block excess calcium ion influx.Methods m[Ca2+] overload in OA mouse bone marrow-derived macrophages (BMDMs) was detected by a fluorescence probe. A tissue in situ fluorescence colocalization assay was used to evaluate METP NP uptake by macrophages. BMDMs from healthy mice were pretreated with a concentration gradient of METP NPs followed by lipopolysaccharide (LPS) stimulation and detection of m[Ca2+] levels in vitro. The optimal METP NP concentration was further applied, and the endoplasmic reticulum (ER) and cytoplasm calcium levels were detected. The inflammatory phenotype was measured by surface markers, cytokine secretion and intracellular inflammatory gene/protein expression. A Seahorse cell energy metabolism assay was performed to elucidate the mechanism by which METP NPs reverse the BMDM proinflammatory phenotype.Results The present study identified calcium overload in BMDM mitochondria of OA mice. We demonstrated that METP NPs reversed the increased m[Ca2+] levels in mitochondria and the proinflammatory phenotype of BMDMs, with both in vivo and in vitro experiments, via the inhibition of the mitochondrial aspartate-arginosuccinate shunt and ROS production.Conclusion We demonstrated that METP NPs are effective and highly specific regulators of m[Ca2+] overload. In addition, we demonstrated that these METP NPs reverse the macrophage proinflammatory phenotype by restoring m[Ca2+] homeostasis, thereby inhibiting the tissue inflammatory response and achieving a therapeutic effect for OA.

CAS / MDL: 590-92-1
研究领域: 药理学 · 纳米技术 · 免疫学 · 骨科 · 细胞生物学
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Nanoscale · 2017 ·Vol. 9 ·期 31 ·11103-11118 · IF 7.367

Mitochondria-targeting near-infrared light-triggered thermosensitive liposomes for localized photothermal and photodynamic ablation of tumors combined with chemotherapy

Caixia Yue,Yuming Yang,Jie Song,Gabriel Alfranca,Chunlei Zhang,Qian Zhang,Ting Yin,Fei Pan,Jesús M. de la Fuente,Daxiang Cui

Lonidamine, an anticancer drug that acts on mitochondria, has poor water solubility. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Hence, a mitochondria-targeting drug delivery system loaded with Lonidamine and a ROS-produced photosensitizer could improve the bioavailability of Lonidamine and maximize photodynamic therapeutic efficiency. Here we report, for the first time, new IR-780 and Lonidamine encapsulated mitochondria-targeting thermosensitive liposomes (IL-TTSL). DSPE-PEG2000-NH2 was coupled with triphenylphosphine to form DSPE-PEG2K-TPP. The liposomes (IL-TTSL) were self-assembled from DPPC, DSPC, DSPE-PEG2K-TPP, cholesterol, IR-780 and Lonidamine. Coupled linker modified triphenylphosphine (TPP) is cationic and can selectively accumulate several hundred-fold within mitochondria. Once the liposomes are located inside mitochondria, 808 nm laser irradiation could trigger photosensitizer IR-780 to elevate the local temperature, which could be utilized in photothermal therapy and induce the release of Lonidamine from the thermosensitive liposomes. Meanwhile, IR-780 could release ROS for photodynamic therapy in mitochondria and increase photodynamic therapeutic efficiency. Our results showed that the surface modification of the liposomes with triphenylphosphine cations had good mitochondria-targeting ability. The liposomes exhibited good biocompatibility and all components of the empty liposomes were safe to be used in humans. Few reports were related to IR-780 being used in photodynamic therapy and we proved this function of IR-780. Overall, the stealth liposomes provide a promising new strategy to realize mitochondria-targeting thermosensitive chemo-, photodynamic and photothermal combination therapy with a single light source for lung cancer.

研究领域: 癌症治疗 · 药物递送系统 · 纳米医学 · 生物医学工程
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Nature Communications · 2024 ·Vol. 15 ·期 1 ·1-10 · IF 14.7

Dual-quartet phosphorescent emission in the open-shell M1Ag13 (M = Pt, Pd) nanoclusters

Fang Cao,Xu Chang,Zhang Wei,Zhou Meng,Tan Dong,Qian Lixia,Hu Daqiao,Jin Shan,Zhu Manzhou

Dual emission (DE) in nanoclusters (NCs) is considerably significant in the research and application of ratiometric sensing, bioimaging, and novel optoelectronic devices. Exploring the DE mechanism in open-shell NCs with doublet or quartet emissions remains challenging because synthesizing open-shell NCs is difficult due to their inherent instability. Here, we synthesize two dual-emissive M 1 Ag 13 (PFBT) 6 (TPP) 7 (M = Pt, Pd; PFBT = pentafluorobenzenethiol; TPP = triphenylphosphine) NCs with a 7-electron open-shell configuration to reveal the DE mechanism. Both NCs comprise a crown-like M 1 Ag 11 kernel with Pt or Pd in the center surrounded by five PPh 3 ligands and two Ag(SR) 3 (PPh 3 ) motifs. The combined experimental and theoretical studies revealed the origin of DE in Pt 1 Ag 13 and Pd 1 Ag 13 . Specifically, the high-energy visible emission and the low-energy near-infrared emission arise from two distinct quartet excited states: the core-shell charge transfer and core-based states, respectively. Moreover, PFBT ligands are found to play an important role in the existence of DE, as its low-lying π * levels result in energetically accessible core-shell transitions. This novel report on the dual-quartet phosphorescent emission in NCs with an open-shell electronic configuration advances insights into the origin of dual-emissive NCs and promotes their potential application in magnetoluminescence and novel optoelectronic devices.

CAS / MDL: 75-09-2 110-54-3 67-56-1
研究领域: 纳米技术 · 材料科学 · 光电技术 · 化学 · 物理
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Nanoscale · 2024 · IF 5.8

Metal–organic framework-based nanoplatforms for synergistic anti-atherosclerosis therapy by regulating the PI3K/AKT/MSR1 pathway in macrophages

Chenlin Zeng,Zhiyou Peng,Sida Huang,Zhijue Xu,Zhaoxi Peng,Zhaoyu Wu,Jiahao Lei,Xing Zhang,Jinbao Qin,Kaichuang Ye,Bo Li,Zhen Zhao,Ying Pan,Minyi Yin,Xinwu Lu

Atherosclerosis is the main pathogenic factor of various cardiovascular diseases. During the pathogenesis of atherosclerosis, macrophages play a major role, mainly by secreting pro-inflammatory cytokines and taking in lipids to form foam cells. Thiamine pyrophosphate (TPP) is an antagonist of the P2Y6 receptor, which is overexpressed on macrophages during atherosclerosis and facilitates the lipid phagocytosis of macrophages. However, the excessive accumulation of TPP may interfere with some vital metabolic processes like the tricarboxylic acid cycle, oxidative phosphorylation and the pentose phosphate pathway. Herein, we designed and constructed a nanoparticle ZIF-8@TPP for the treatment of atherosclerosis. The as-established ZIF-8@TPP nanoplatform exhibited specific cytotoxicity towards macrophages in vitro. Meanwhile, histological analysis confirmed the excellent therapeutic efficacy of ZIF-8@TPP in vivo. Mechanistic studies indicated that ZIF-8@TPP potentially lowered lipid phagocytosis and lipid metabolism of macrophages via the PI3K/AKT/MSR1 pathway. This study also demonstrated that the anti-atherosclerotic effect of TPP was enhanced after combination with a prototypical metal–organic framework (MOF), ZIF-8. This synergistic controlled-release drug delivery system may provide a novel idea for anti-atherosclerosis therapy by combining reagents that can inhibit lipid phagocytosis of macrophages with MOFs.

研究领域: 心血管疾病 · 药理学 · 纳米技术 · 分子生物学
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POLYMERS FOR ADVANCED TECHNOLOGIES · 2022 ·Vol. 33 ·期 10 ·3192-3200 · IF 3.348

Microparticle-hydrogel hybrids for sustained release of dual bioactive compounds

Zhicheng Deng,Jinjun Li,Yun Chen,Chao Huang,Nanjing Zhong,Yong Hu

A novel Cur/TPP-β-CD/CS/Vc microparticles (MPs) filled CMCS/OSA composite hydrogel was prepared by dispersed the chitosan/vitamin C (CS/Vc) complex and curcumin/TPP-β-cyclodextrin (Cur/TPP-β-CD) complex in the hydrogel precursor of oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMCS). Structural properties of the MPs/CMCS/OSA composite hydrogel were characterized by Fourier transform infrared, scanning electron microscope, TG, rheological, and texture analyzer. It was found that the polymeric MPs with a diameter of about 2.5 μm were homogenously embedded in the composite hydrogel by hydrogen bonding and electronic force, resulting in obvious enhanced mechanical strength and stability of the MPs hybrid hydrogel. In vitro release studies show that the release of Cur and Vc can be more efficiently controlled by the different encapsulation pathways. Moreover, the preferential release of the Cur than that of Vc has been confirmed by the two-dimensional ultraviolet correlation spectroscopy. Therefore, the MPs/CMCS/OSA composite hydrogel can be used for independently controlled release of dual bioactive compounds during codelivery.

CAS / MDL: 9012-76-4
研究领域: 药学 · 材料科学 · 生物技术 · 药物递送系统
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