Mengmeng Hou

Air Force Medical University

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Peng Xue

Southwest University

Zhigang Xu

Southwest University

Yuejun Kang

Southwest University

Xiaomin Li

Collaborative Innovation Center of Chemistry for Energy Materials

Minchao Liu

Fudan University

Yufang Kou

Fudan University

Hongyue Yu

Collaborative Innovation Center of Chemistry for Energy Materials

Ruihao Yang

Shanghai Jiao Tong University

Tiancong Zhao

Collaborative Innovation Center of Chemistry for Energy Materials

Fan Zhang

Jinan University

Cooperative Institutions

Fudan University

Hebei Medical University

Third Hospital of Hebei Medical University

Chinese Academy of Sciences

Collaborative Innovation Center of Chemistry for Energy Materials

Air Force Medical University

Shanghai Stomatological Hospital

Chinese Academy of Medical Sciences & Peking Union Medical College

Xijing Hospital

Huazhong University of Science and Technology

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Core@paratroopers Nanoassemblies with Catalytic Cascade for Efficient Tumor Starvation Therapy

Advanced Functional Materials (2024)

Qianqian Lu Mengmeng Hou Xirui Huang Hongyue Yu Xingjin Li

Abstract The catalytic therapy based on the nanozymes has received increasing interest in cancer treatment. However, the catalytic capabilities of standalone nanozymes are relatively limited, necessitating the development of a nano‐bio composite system that integrates both nanozymes and natural enzymes. This construction often inevitably leads to interference between natural enzyme and nanozymes, resulting in reduced synergistic performance. Herein, a cascade catalysis system featuring the “core@paratroopers” structure is proposed, wherein hollow manganese dioxide (HMnO 2 ) serves as “core” and ultra‐small hybrid single‐micelle (H‐micelle) encapsulated with glucose oxidase (GOx) as “paratroopers” (H‐micelle‐GOx). The outer SiO 2 layer of the H‐micelle can effectively protect the GOx. Under hypoxic conditions, HMnO 2 reacts with endogenous H 2 O 2 to produce O 2 , thereby enhancing the catalytic efficiency of GOx for starvation therapy. Simultaneously, the generated H 2 O 2 boosts the catalytic efficiency of HMnO 2 , accelerating local O 2 generation and alleviating tumor hypoxia. Additionally, this system exhibits rapid degradation in the tumor microenvironment characterized by high glutathione (GSH) expression, facilitating the release and deep penetration of the ultra‐small H‐micelle‐GOx “paratroopers” within the solid tumor.

Glucose oxidase

10.1002/adfm.202401328

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Mitofusin-2 gene polymorphisms and metabolic dysfunction associated fatty liver disease: a case-control study in a Chinese population

Journal of International Medical Research (2023)

Xiwei Yuan Mengmeng Hou Yiqi Wang Siyu Zhang Lu Li

Mitofusion-2 (Mfn2) may have a role in mitochondrial oxidative stress and insulin resistance that can promote the development of metabolic dysfunction associated fatty liver disease (MAFLD). This retrospective and case control study aimed to explore the relationships between common Mfn2 single nucleotide polymorphisms (SNPs) and MAFLD in a northern Han Chinese population.Six Mfn2 SNPs (rs2336384, rs873458, rs873457, rs4846085, rs2878677, and rs2236057) were genotyped using the ligase detection reaction in 466 MAFLD patients and 423 healthy controls. Genotype and allele frequencies were calculated, along with haplotype analysis and pairwise linkage disequilibrium.The genotype distribution of rs2336384, rs2878677, and rs2236057 among the MAFLD patients showed a significantly different pattern from that of healthy controls. The data showed that an increased risk of MAFLD was significantly correlated with patients carrying the GG genotype of rs2336384, CC genotype of rs873457, TT genotype of rs4846085, TT genotype of rs2878677, and the AA genotype of rs2236057. Moreover, The GGCTTA haplotype was found to be adversely linked with MAFLD by haplotype analysis.The current findings suggest a strong link between certain Mfn2 gene polymorphisms and MAFLD.

10.1177/03000605231187953

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Citations (1)

PEGDA/PVP Microneedles with Tailorable Matrix Constitutions for Controllable Transdermal Drug Delivery

Macromolecular Materials and Engineering (2018)

Ya Gao Mengmeng Hou Ruihao Yang Lei Zhang Zhigang Xu

Abstract Polymeric microneedles have attracted increasing interest for transdermal drug delivery owing to the unique advantages of minimal invasiveness, biocompatibility, biodegradability, and efficient drug‐loading capacity. However, drug release from polymeric microneedles lacks controllability during transdermal administration. Herein, a poly(ethylene glycol) diacrylate/polyvinylpyrrolidone (PEGDA/PVP) microneedle patch with tailorable matrix constitutions is designed and fabricated using a two‐step ultraviolet (UV) light‐induced polymerization method. Scanning electron microscopic characterization reveals a non‐uniform interior matrix of microneedles, resulting from the aggregation of PVP in the polymerized PEGDA matrix induced by UV irradiation. The fabricated microneedles are found to show sufficient mechanical strength for skin penetration and they can be removed intact after application. The controllable release property of rhodamine B (RhB)‐loaded PEGDA/PVP microneedles is demonstrated in vitro by tuning the fraction of PVP content. The typical characteristics including initial burst and subsequent sustained release are attributed to the rapid dissolution of PVP and prolonged swelling of PEGDA, respectively. In addition, the microneedle insertion site can be completely recovered within 1 h on a porcine skin, indicating the minimally invasive feature of microneedle‐mediated therapeutic delivery. This scalable microneedle platform may serve as a convenient and effective drug carrier for transdermal delivery of various pharmaceuticals under precise control.

Biocompatibility

Rhodamine B

Polyvinylpyrrolidone

10.1002/mame.201800233

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Transdermal delivery of therapeutics through dissolvable gelatin/sucrose films coated on PEGDA microneedle arrays with improved skin permeability

Journal of Materials Chemistry B (2019)

Ya Gao Mengmeng Hou Ruihao Yang Lei Zhang Zhigang Xu

Microneedles are primarily designed for enhancing transdermal drug delivery in a minimally invasive manner.

Gelatin

10.1039/c9tb01994d

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Citations (41)

Traditional Chinese medicine Yiqi Huoxue recipe attenuates hepatic fibrosis via YAP/TAZ signaling.

PubMed (2021)

Wen Zhao Xiaoxiao Zhang Mengmeng Hou Yuguo Zhang Yuhui Tang

The Yiqi Huoxue (YQHX) recipe has been shown to attenuate liver fibrosis, but precise mechanisms have not yet been elucidated. Recently, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling has been implicated in liver fibrogenesis. This study investigated whether the YAP/TAZ signaling is involved in the therapeutic effect of YQHX on hepatic fibrosis.

Hepatic fibrosis

CCL4

10.14670/hh-18-373

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Heme oxygenase 1 alleviates nonalcoholic steatohepatitis by suppressing hepatic ferroptosis

Lipids in Health and Disease (2023)

Xiwei Yuan Lu Li Ying Zhang Rong Ai Dong‐Dong Li

Abstract Background Heme oxygenase 1 (HO-1) has an influential but insufficiently investigated effect on ferroptosis, which is a novel form of programmed cell death and may play an effect on nonalcoholic steatohepatitis (NASH). However, the understanding of the mechanism is limited. Herein, our study aimed to explore the mechanism and role of HO-1 in NASH ferroptosis. Methods Hepatocyte conditional HO-1 knockout (HO-1 HEPKO ) C57BL/6J mice were established and fed a high-fat diet (HFD). Additionally, wild-type mice were fed either a normal diet or a HFD. Hepatic steatosis, inflammation, fibrosis, lipid peroxidation, and iron overload were assessed. AML12 and HepG2 cells were used to investigate the underlying mechanisms in vitro. Finally, liver sections from NASH patients were used to clinically validate the histopathology of ferroptosis. Results In mice, HFD caused lipid accumulation, inflammation, fibrosis, and lipid peroxidation, which were aggravated by HO-1 HEPKO . In line with the in vivo results , HO-1 knockdown upregulated reactive oxygen species accumulation, lipid peroxidation, and iron overload in AML12 and HepG2 cells. Additionally, HO-1 knockdown reduced the GSH and SOD levels, which was in contrast to HO-1 overexpression in vitro. Furthermore, the present study revealed that the NF-κB signaling pathway was associated with ferroptosis in NASH models. Likewise, these findings were consistent with the liver histopathology results of NASH patients. Conclusion The current study showed that HO-1 could alleviate NASH progression by mediating ferroptosis.

Nonalcoholic steatohepatitis

Lipidology

Steatohepatitis

Biliverdin

10.1186/s12944-023-01855-7

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Citations (11)

Ternary Heteronanocrystals with Dual-Heterojunction for Boosting Near-Infrared-Triggered Photo-Chemodynamic Therapy

Journal of the American Chemical Society (2024)

Yufang Kou Minchao Liu Mengmeng Hou Tiancong Zhao Liang Chen

Strongly coupled interfaces in the epitaxial growth heteronanocrystals (HNCs) provide advanced functionalities regarding interface connection, electron transfer, and carrier separation. However, the majority of current nanocomposites primarily focus on a single heterojunction involving only two subunits, which hinders the achievement of optimized synergy energy transfer among more than two components. Herein, ternary NaGdF

Ternary complex

10.1021/jacs.4c15819

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Surface curvature-induced oriented assembly of sushi-like Janus therapeutic nanoplatform for combined chemodynamic therapy

Journal of Nanobiotechnology (2023)

Yanming Ma Minchao Liu Mengmeng Hou Yufang Kou Wenxing Wang

Chemodynamic therapy (CDT) based on Fenton/Fenton-like reaction has emerged as a promising cancer treatment strategy. Yet, the strong anti-oxidation property of tumor microenvironment (TME) caused by endogenous glutathione (GSH) still severely impedes the effectiveness of CDT. Traditional CDT nanoplatforms based on core@shell structure possess inherent interference of different subunits, thus hindering the overall therapeutic efficiency. Consequently, it is urgent to construct a novel structure with isolated functional units and GSH depletion capability to achieve desirable combined CDT therapeutic efficiency.Herein, a surface curvature-induced oriented assembly strategy is proposed to synthesize a sushi-like novel Janus therapeutic nanoplatform which is composed of two functional units, a FeOOH nanospindle serving as CDT subunit and a mSiO2 nanorod serving as drug-loading subunit. The FeOOH CDT subunit is half covered by mSiO2 nanorod along its long axis, forming sushi-like structure. The FeOOH nanospindle is about 400 nm in length and 50 nm in diameter, and the mSiO2 nanorod is about 550 nm in length and 100 nm in diameter. The length and diameter of mSiO2 subunit can be tuned in a wide range while maintaining the sushi-like Janus structure, which is attributed to a Gibbs-free-energy-dominating surface curvature-induced oriented assembly process. In this Janus therapeutic nanoplatform, Fe3+ of FeOOH is firstly reduced to Fe2+ by endogenous GSH, the as-generated Fe2+ then effectively catalyzes overexpressed H2O2 in TME into highly lethal ·OH to achieve efficient CDT. The doxorubicin (DOX) loaded in the mSiO2 subunit can be released to achieve combined chemotherapy. Taking advantage of Fe3+-related GSH depletion, Fe2+-related enhanced ·OH generation, and DOX-induced chemotherapy, the as-synthesized nanoplatform possesses excellent therapeutic efficiency, in vitro eliminating efficiency of tumor cells is as high as ~ 87%. In vivo experiments also show the efficient inhibition of tumor, verifying the synthesized sushi-like Janus nanoparticles as a promising therapeutic nanoplatform.In general, our work provides a successful paradigm of constructing novel therapeutic nanoplatform to achieve efficient tumor inhibition.

Nanorod

10.1186/s12951-023-02138-0

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Black Titania Janus Mesoporous Nanomotor for Enhanced Tumor Penetration and Near-Infrared Light-Triggered Photodynamic Therapy

ACS Nano (2024)

Kexin Lv Mengmeng Hou Yufang Kou Hongyue Yu Mengli Liu

Thanks to their excellent photoelectric characteristics to generate cytotoxic reactive oxygen species (ROS) under the light-activation process, TiO2 nanomaterials have shown significant potential in photodynamic therapy (PDT) for solid tumors. Nevertheless, the limited penetration depth of TiO2-based photosensitizers and excitation sources (UV/visible light) for PDT remains a formidable challenge when confronted with complex tumor microenvironments (TMEs). Here, we present a H2O2-driven black TiO2 mesoporous nanomotor with near-infrared (NIR) light absorption capability and autonomous navigation ability, which effectively enhances solid tumor penetration in NIR light-triggered PDT. The nanomotor was rationally designed and fabricated based on the Janus mesoporous nanostructure, which consists of a NIR light-responsive black TiO2 nanosphere and an enzyme-modified periodic mesoporous organosilica (PMO) nanorod that wraps around the TiO2 nanosphere. The overexpressed H2O2 can drive the nanomotor in the TME under catalysis of catalase in the PMO domain. By precisely controlling the ratio of TiO2 and PMO compartments in the Janus nanostructure, TiO2&PMO nanomotors can achieve optimal self-propulsive directionality and velocity, enhancing cellular uptake and facilitating deep tumor penetration. Additionally, by the decomposition of endogenous H2O2 within solid tumors, these nanomotors can continuously supply oxygen to enable highly efficient ROS production under the NIR photocatalysis of black TiO2, leading to intensified PDT effects and effective tumor inhibition.

Penetration (warfare)

10.1021/acsnano.4c03652

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Injectable and Natural Humic Acid/Agarose Hybrid Hydrogel for Localized Light-Driven Photothermal Ablation and Chemotherapy of Cancer

ACS Biomaterials Science & Engineering (2018)

Mengmeng Hou Ruihao Yang Lei Zhang Leiyang Zhang Gang Liu

The injection of theranostic drug-laden hydrogels into subcutaneous tumors has proven to be a promising strategy to achieve precise local tumor eradication. Humic acid, a natural product of biochemical decomposition of animal and plant residues, abundantly exists in soils, peats, oceans, etc. In this study, a robust injectable thermoresponsive agarose hydrogel incorporating sodium humate (SH) and doxorubicin (DOX) was constructed as a unique agent for tumor management based on the combined chemo-photothermal therapeutic effect. SH, which strongly absorbs near-infrared (NIR) light, can efficiently convert light energy into thermal energy, induce local hyperthermia and subsequently trigger sustained drug release from the complex of the SH/DOX@hydrogel through a typical gel–sol transition, resulting in enhanced cellular uptake of therapeutic drugs. Moreover, intratumoral injection of the SH/DOX@hydrogel resulted in a simultaneous chemo-photothermal therapeutic effect against solid tumors under NIR laser irradiation, which may collectively prevent tumor recurrence. In addition, the SH/DOX@hydrogel exhibited ultralow systemic toxicity as demonstrated using an animal model. This work provides a promising attempt to develop a low-cost, light-responsive hydrogel for precise tumor therapy, which may also incorporate extra theranostic modules as an advanced platform for the treatment of cancer or other critical diseases.

Agarose

Photothermal effect

10.1021/acsbiomaterials.8b01147

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Citations (52)