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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-14 · IF 10.6

Rescue of nucleus pulposus cells from an oxidative stress microenvironment via glutathione-derived carbon dots to alleviate intervertebral disc degeneration

Bu Wenzhen,Shi Yu,Huang Xueping,Wu Shang,Jiang Letao,Pan Chun,Li Dandan,Xu Zhuobin,Wang Huihui,Chen Hao,Du Jianwei

The senescence of nucleus pulposus (NP) cells (NPCs), which is induced by the anomalous accumulation of reactive oxygen species (ROS), is a major cause of intervertebral disc degeneration (IVDD). In this research, glutathione-doped carbon dots (GSH-CDs), which are novel carbon dot antioxidant nanozymes, were successfully constructed to remove large amounts of ROS for the maintenance of NP tissue at the physical redox level. After significantly scavenging endogenous ROS via exerting antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity, GSH-CDs with good biocompatibility have been demonstrated to effectively improve mitochondrial dysfunction and rescue NPCs from senescence, catabolism, and inflammatory factors in vivo and in vitro. In vivo imaging data and histomorphological indicators, such as the disc height index (DHI) and Pfirrmann grade, demonstrated prominent improvements in the progression of IVDD after the topical application of GSH-CDs. In summary, this study investigated the GSH-CDs nanozyme, which possesses excellent potential to inhibit the senescence of NPCs with mitochondrial lesions induced by the excessive accumulation of ROS and improve the progression of IVDD, providing potential therapeutic options for clinical treatment.Graphical Abstract

CAS / MDL: 7722-84-1 19660-77-6
研究领域: 生物医学工程 · 纳米技术 · 骨科 · 细胞生物学 · 组织工程
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BIOMATERIALS · 2024 · IF 12.8

Regulatory T Cells Engineered with Polyphenol-Functionalized Immunosuppressant Nanocomplexes for Rebuilding Periodontal Hard Tissue under Inflammation-Challenged Microenvironment

Bo Zhang,Guidong Gong,Yunxiang He,Jialing Liu,Bo Wang,Yifei Li,Jie Fang,Zhihe Zhao,Junling Guo

Global aging heightens the risk of oral disorders, among which periodontitis is the major cause of tooth loss in the aging population. The regeneration of damaged periodontal hard tissue is highly challenging due to the existence of the refractory local inflammation. Owing to the potent anti-inflammatory capabilities, regulatory T cells hold great promise in immunotherapies for tissue regeneration. However, the transferred regulatory T cells can alter their phenotypes and functions in local inflammatory milieu, significantly impairing their therapeutic efficacy. Herein, we introduce a novel regulatory T cell-based nanobiohybrid system bearing polyphenol-functionalized rapamycin nanocomplexes. The sustained in situ release of immunosuppressant rapamycin from the cell-attached nanocomplexes maintains the anti-inflammatory phenotype of regulatory T cells in the inflammatory milieu. The synergistic actions of the anti-inflammatory cytokines secreted and the immunosuppressant released guide a pro-resolving polarization of macrophages and enhance osteogenic differentiation of bone marrow-derived stromal cells. The stabilized phenotype of the regulatory T cells dramatically promoted the resolution of periodontal inflammation and the repair of the hard tissue (alveolar bone) in vivo . Overall, these studies highlight a potent regulatory T cell-based nanobiohybrid therapy to treat periodontitis by modulating periodontal immune microenvironment.

CAS / MDL: 19660-77-6
研究领域: 免疫学 · 纳米技术 · 牙科科学 · 组织工程 · 生物医学工程
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CARBOHYDRATE POLYMERS · 2024 · IF 10.7

Fucoidan based Ce6-chloroquine self-assembled hydrogel as in situ vaccines to enhance tumor immunotherapy by autophagy inhibition and macrophage polarization

Teng Wang,Yu Wang,Bingjie Wang,Yanguo Su,Tianze Jiang,Tiantian Gan,Xia Zhao

Tumor vaccines have become a promising approach for cancer treatment by triggering antigen-specific responses against tumors. However, autophagy and immunosuppressive tumor microenvironment (TME) reduce antigen exposure and immunogenicity, which limit the effect of tumor vaccines. Here, we develop fucoidan (Fuc) based chlorin e6 (Ce6)-chloroquine (CQ) self-assembly hydrogels (CCFG) as in situ vaccines. Ce6 triggers immune response in situ by photodynamic therapy (PDT) induced immunogenic cell death (ICD) effect, which is further enhanced by macrophage polarization of Fuc and autophagy inhibition of CQ. In vivo studies show that CCFG effectively enhances antigen presentation under laser irradiation, which induces a powerful in situ vaccine effect and significantly inhibits tumor metastasis and recurrence. Our study provides a novel approach for enhancing tumor immunotherapy and inhibiting tumor recurrence and metastasis.

CAS / MDL: 54-05-7 19660-77-6
研究领域: 肿瘤学 · 免疫学 · 药学 · 生物医学工程
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2025 · IF 4.9

Exploration of using α-crocin for drug encapsulation and delivery

Yuanxin Pian,Yan Hao,Yuxin Guo,Shiqi Wu,Saijiao Tang,Jiaqi Li,Xinya Lu,Xiaoya Sun,Zhaowen Tan,Tianyu Zhu,Yuxiang Tang,Defeng Xu,Hang Hu

Facile and efficient drug loading and delivery strategies hold paramount importance in the development of advanced pharmaceutical formulations, enhancing both the efficacy and accessibility of treatments. In this study, we successfully prepared dimethylcurcumin (DMC)-loaded α-crocin nanoparticles with varying drug loadings (15.2 % and 21.7 %) using a solvent diffusion method, which exhibit excellent lyophilization stability, relatively small and uniform particle sizes. DMC is encapsulated in an amorphous state within α-crocin nanoparticles, forming strong π-π stacking interactions. Dissipative particle dynamics simulations and transmission electron microscope images confirm the core-shell structure, with DMC aggregates forming the cores and α-crocin coating the surfaces. The drug loading studies on various drugs with different structure and properties show that hydrophobic drugs with π-conjugated systems and planar structures can be efficiently encapsulated with α-crocin. The nanoparticles exhibit sustained drug release in pH 7.4 and pH 5.0 conditions and demonstrate enhanced antitumor activity in vitro compared to free drugs, with DMC@α-Crocin (15.2 %) nanoparticles showing superior performance due to higher cellular uptake. Pharmacokinetic study reveals prolonged blood half-life and increased area under curve for DMC@α-Crocin (15.2 %) nanoparticles, indicating improved drug delivery. This work validates the potential of α-crocin-based drug encapsulation for enhanced cellular uptake, antitumor activity, and prolonged blood circulation, providing new insights into the development of efficient drug delivery system.

研究领域: 药剂学 · 生物医学工程 · 纳米医学
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Advanced Healthcare Materials · 2024 · IF 10

Multitasking Asynchronous Collaborative Nanosystem for Diabetic Wound Healing Based on Hypoglycemic, Antimicrobial, and Angiogenesis-Promoting Effects

Jun Ren,Chaoli Wang,Hao Gao,Shuaikun Lu,Congxiao Fu,Hu Wang,Guoliang Wang,Zhenfeng Zhu,Hong Wu,Wen Luo,Yunfei Zhang

A diabetic foot ulcer (DFU) is a common and serious complication of diabetes. This complication can result in amputation and death because of the several challenges associated with wound healing that can be attributed to the complex wound microenvironment, including biofilm infection, hyperglycemia, and diabetic angiopathy. Existing investigations on the wound-healing rate consider only one or two pathogenic factors, and therefore, despite the extensive research on these pathological microenvironments, there is an urgent need to optimize the wound-healing rate in patients with diabetic foot ulcers. To this end, a multitasking asynchronous collaborative nanosystem is designed in this study. The designed nanosystem can efficiently clear biofilm infections using optimized photodynamic therapy based on a poly photosensitizer ionic liquid (i.e., Ce6IL), reduce local blood glucose concentration using glucose oxidase, and reconstruct blood vessels by stimulating endothelial cell proliferation and migration using nitric oxide. The experimental results indicate that the three-step sequential collaboration strategy for clearing biofilm infections, reducing glucose concentrations, and reconstructing damaged blood vessels can help significantly accelerate wound healing rate in patients with diabetic foot ulcers.

研究领域: 生物医学工程 · 药理学 · 糖尿病研究
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Acta Pharmaceutica Sinica B · 2024 · IF 14.7

Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy

Zaigang Zhou,Wenjuan Luo,Chunjuan Zheng,Haoxiang Wang,Rui Hu,Hui Deng,Jianliang Shen

Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to the impaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution. Meanwhile, acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1 (PD-L1) expression after PTX@Alb treatment, which then leads to immune tolerance. To fill these gaps, we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer with mitochondrial metabolism blockade capacity, could also be used as a novel effective PD-L1 and TGF- β dual-inhibitor via inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase (AMPK) protein. Following this, to obtain a more significant effect, TPP-TAM was prepared by conjugating mitochondria-targeted triphenylphosphine (TPP) with TAM, which then further self-assembled with albumin (Alb) to form TPP-TAM@Alb nanoparticles. By doing this, TPP-TAM@Alb nanoparticles effectively decreased the expression of collagen in vitro , which then led to the enhanced accumulation of PTX@Alb in 4T1 tumors. Besides, TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF- β in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cell infiltration. All in all, we newly put forward a novel mitochondrial metabolism blockade strategy to inhibit PTX@Alb-resistant tumors, further supporting its better clinical application.

研究领域: 肿瘤学 · 药理学 · 免疫学 · 纳米技术
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Near-Infrared Optogenetic Nanosystem for Spatiotemporal Control of CRISPR-Cas9 Gene Editing and Synergistic Photodynamic Therapy

Junyi Zeng,Xinbo Huang,Yajie Yang,Jieyi Wang,Yuanchao Shi,Hui Li,Ning Hu,Bo Yu,Jing Mu

Controlling CRISPR/Cas9 gene editing at the spatiotemporal resolution level, especially for in vivo applications, remains a great challenge. Here, we developed a near-infrared (NIR) light-activated nanophotonic system (UCPP) for controlled CRISPR-Cas9 gene editing and synergistic photodynamic therapy (PDT). Lanthanide-doped upconversion nanoparticles are not only employed as carriers for intracellular plasmid delivery but also serve as the nanotransducers to convert NIR light (980 nm) into visible light with emission at 460 and 650 nm, which could result in simultaneous activation of gene editing and PDT processes, respectively. Such unique design not only achieves light-controlled precise gene editing of hypoxia-inducible factor 1α with minimal off-target effect, which effectively ameliorates the hypoxic state at tumor sites, but also facilitates the deep-seated PDT process with synergistic antitumor effect. This optogenetically activatable CRISPR-Cas9 nanosystem holds great potential for spatially controlled in vivo gene editing and targeted cancer therapy.

研究领域: 生物医学工程 · 分子生物学 · 基因治疗 · 癌症研究 · 纳米技术
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PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES · 2025 · IF 3.2

A zeolite imidazolate (ZIF-8)-based system for synergistic photodynamic/starvation therapy of breast cancer

Li Fenglan,Zhang Yuanyuan,Ye Chenliu,Zhuang Junyang

The treatment of breast cancer (BC) faces multiple challenges, including high recurrence rates, drug resistance, and toxic side effects. This study constructed a cell membrane-mimicking biomimetic cascade nanoreactor, mCGH@ZIF, which is loaded with the photosensitizer chlorin e6 (Ce6), glucose oxidase (GOx), and hemin, enabling synergistic starvation-photodynamic therapy. Within the tumor microenvironment, GOx depleted glucose and generated H₂O₂; hemin converted H₂O₂ into O₂ in situ, effectively alleviated hypoxia and amplified the generation of Ce6-mediated singlet oxygen; and the cancer cell membrane coating enabled both immune evasion and homologous targeting. In vitro experiments demonstrated that mCGH@ZIF significantly suppressed 4T1 breast cancer cell proliferation while preserving excellent biocompatibility. This strategy established a closed-loop system integrating glucose depletion, oxygen production, and reactive oxygen species (ROS) generation, overcame the limitations of monotherapies, and offered a novel approach for precision combination therapy in breast cancer.

CAS / MDL: 16009-13-5 19660-77-6
研究领域: 纳米医学 · 癌症治疗 · 光动力治疗 · 药物递送系统 · 生物材料
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ADVANCED MATERIALS · 2021 ·Vol. 33 ·期 7 ·2005562 · IF 30.849

Self-Activatable Photo-Extracellular Vesicle for Synergistic Trimodal Anticancer Therapy

Jingjing Ding,Guihong Lu,Weidong Nie,Li-Li Huang,Yahui Zhang,Wenlin Fan,Guanghao Wu,Houli Liu,Hai-Yan Xie

Extracellular vesicles (EVs) hold great potential in both disease treatment and drug delivery. However, accurate drug release from EVs, as well as the spontaneous treatment effect cooperation of EVs and drugs at target tissues, is still challenging. Here, an engineered self-activatable photo-EV for synergistic trimodal anticancer therapy is reported. M1 macrophage-derived EVs (M1 EVs) are simultaneously loaded with bis[2,4,5-trichloro-6-(pentyloxycarbonyl) phenyl] oxalate (CPPO), chlorin e6 (Ce6), and prodrug aldoxorubicin (Dox-EMCH). After administration, the as-prepared system actively targets tumor cells because of the tumor-homing capability of M1 EVs, wherein M1 EVs repolarize M2 to M1 macrophages, which not only display immunotherapy effects but also produce H 2 O 2 . The reaction between H 2 O 2 and CPPO generates chemical energy that activates Ce6, creating both chemiluminescence for imaging and singlet oxygen ( 1 O 2 ) for photodynamic therapy (PDT). Meanwhile, 1 O 2 -induced membrane rupture leads to the release of Dox-EMCH, which is then activated and penetrates the deep hypoxic areas of tumors. The synergism of immunotherapy, PDT, and chemotherapy results in potent anticancer efficacy, showing great promise to fight cancers.

CAS / MDL: 75203-51-9 19660-77-6
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Nanoscale · 2020 ·Vol. 12 ·期 43 ·22173-22184 · IF 6.895

Ce6-Conjugated and polydopamine-coated gold nanostars with enhanced photoacoustic imaging and photothermal/photodynamic therapy to inhibit lung metastasis of breast cancer

Ziwei Li,Fan Yang,Di Wu,Yanhong Liu,Yang Gao,Haichen Lian,Hongxin Zhang,Zhibin Yin,Aiguo Wu,Leyong Zeng

Metastasis is the main cause of treatment failure in breast cancer, and integrated phototheranostics is a promising strategy to achieve both precision theranostics and metastasis inhibition. In this work, a multifunctional phototheranostic nanoprobe composed of chlorin e6 (Ce6)-conjugated and polydopamine (PDA)-coated gold nanostars (AuNSs) was synthesized for simultaneous photoacoustic (PA) imaging, photothermal therapy (PTT) and photodynamic therapy (PDT). Under the irradiation of near infrared laser, AuNSs@PDA showed enhanced photothermal conversion and amplified PA imaging performance, compared with single AuNSs. By the covalent conjugation of Ce6, the AuNSs@PDA-Ce6 nanoprobe showed robust stability and excellent singlet oxygen (1O2) generation ability. Under the combination of PTT/PDT, the AuNSs@PDA-Ce6 nanoprobes significantly reduced the growth of 4T1 tumors and suppressed their lung metastasis. All the results demonstrated the considerable potential of AuNSs@PDA-Ce6 phototheranostic nanoprobes for precision theranostics and metastasis inhibition of breast cancer.

研究领域: 纳米技术 · 癌症研究 · 治疗诊断学 · 生物医学工程
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Advanced Science · 2021 ·Vol. 8 ·期 16 ·2100228 · IF 16.806

Photoacoustic Force-Guided Precise and Fast Delivery of Nanomedicine with Boosted Therapeutic Efficacy

Jun Wang,Tingting Li,Jen-Shyang Ni,Heng Guo,Tianyi Kang,Zeshun Li,Menglei Zha,Songbo Lu,Chen Zhang,Weizhi Qi,Lei Xi,Kai Li

Precise and efficient delivery of nanomedicine to the target site has remained as a major roadblock in advanced cancer treatment. Here, a novel photoacoustic force (PAF)-guided nanotherapeutic system is reported based on a near-infrared (NIR)-absorbing semiconducting polymer (SP), showing significantly improved tumor accumulation and deep tissue penetration for enhanced phototherapeutic efficacy. The accumulation of nanoparticles in 4T1 tumor-bearing mice induced by the PAF strategy displays a fivefold enhancement in comparison with that of the traditional passive targeting pathway, in a significantly shortened time (45 min vs 24 h) with an enhanced penetration depth in tumors. Additionally, a tumor-bearing mouse model is rationally designed to unveil the mechanism, indicating that the nanoparticles enter solid tumors through enhanced transportation across blood vessel barriers via both inter-endothelial gaps and active trans-endothelial pathways. This process is specifically driven by PAF generated from the nanoparticles under NIR laser irradiation. The study thus demonstrates a new nanotherapeutic strategy with low dose, enhanced delivery efficiency in tumor, and boosted therapeutic efficacy, opening new doors for designing novel nanocarriers.

研究领域: 生物医学工程 · 癌症治疗 · 纳米医学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2024 · IF 5.4

A multifunctional graphene oxide-based nanodrug delivery system for tumor targeted diagnosis and treatment under chemotherapy-photothermal-photodynamic synergy

Huirui Zhu,Ruolan Feng,Dongkun Li,Meijuan Shi,Nan Wang,Yijie Wang,Yumeng Guo,Xiaoning Li,Tao Gong,Rui Guo

Traditional cancer therapies, such as chemotherapy, often lack specificity, resulting in severe toxic side effects and limited therapeutic efficacy. There is an urgent need to develop innovative multifunctional nanomedicine carriers that integrate precise diagnosis, targeted therapy, real-time monitoring, and the synergistic effects of multiple therapeutic approaches. In this study, a composite nanodrug delivery system (GO-HA-Ce6-GNRs) based on graphene oxide (GO) was innovatively prepared, which was functionalized with the targeting molecule hyaluronic acid (HA), the photosensitizer chlorin e6 (Ce6), and the photothermal material gold nanorods (GNRs). In vitro and in vivo experiments demonstrated that GO-HA-Ce6-GNRs exhibited excellent biocompatibility, remarkable photothermal and photodynamic properties, high drug-loading capacity for the anticancer drug doxorubicin hydrochloride (DOX), and a dual pH/near-infrared (NIR) light-responsive drug release profile. Additionally, GO-HA-Ce6-GNRs displayed enhanced tumor targeting and efficient fluorescence imaging capabilities. Notably, GO-HA-Ce6-GNRs@DOX manifested highly effective chemotherapy-photothermal-photodynamic synergistic anti-tumor effects in both MCF-7 and HeLa cancer cells as well as U14 tumor-bearing mice. Therefore, GO-HA-Ce6-GNRs@DOX represents a promising nanoplatform for tumor diagnosis and therapy, significantly improving the safety and efficacy of chemotherapy. This work provides a solid foundation and theoretical basis for the development of new targeted nano drug delivery systems that integrate both diagnosis and treatment.

研究领域: 生物医学工程 · 药学 · 肿瘤学
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