Advanced Healthcare Materials
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2024
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IF 10
Weisin Chen,Hongwei Lu,Wenhao Yu,Lei Huang,Mengxuan Bian,Ning Wang,Xingdong Xiang,Guokang Mo,Cheng Zhang,Yulin Li,Libo Jiang,Jian Zhang
Autograft has long been the gold standard for various bone surgeries. Nevertheless, the increasing usage of synthetic implants is taking over the operation rooms due to biosafety and standardized protocols. To fulfill such tremendous needs, a magnesium-impregnated membrane is devised that steadily releases magnesium ions to stimulate osteogenesis. The compatibility of Magnesium oxide (MgO) particles is enhanced through hydration and grafting, characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). With detailed degradation profiles, an in-depth investigation of Magnesium transporter 1 (MagT1) for magnesium intake is carried out and engaging in the N-linked glycosylation by using RNAi and inhibitors. The glycosylation of secreted protein acidic and rich in cysteine (SPARC) affected extracellular secretion and mineral deposition, demonstrated by immunostaining and density-dependent color-SEM (DDC-SEM). Skull defects are treated by implanting magnesium-impregnated membranes in rats and evaluated them by micro-CT and histological exams. This study revealed the compatible integration of grafted magnesium hydroxide (g-MH) particles is the key to functional performance and critical to applicability in vivo; meanwhile, it opens the door to a biological rationale for designing biomimetic materials.
研究领域:
生物医学工程
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分子生物学
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材料科学
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DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2025
·Vol. 82
·期 1
·1-16
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IF 6.2
Du Li,Cui Yinghong,Chen Wei,Li Chunyun,He Zuping
Sertoli cell-only syndrome (SCOS) is one of the most severe non-obstructive azoospermia (NOA) types, since only Sertoli cells with not any male germ cells exist with the seminiferous tubules. As such, it is of particular significance to elucidate molecular mechanisms underlying SCOS for improving the diagnosis and treatment strategies for this disease. Due to the difficulties in obtaining sufficient human testicular tissues and the limited availability of human cells, the traditional proteomics is inadequate for comparing the differences in large scale of protein expression patterns of human Sertoli cells between SCOS and normal men. To solve this issue on the requirement of large amount of cell numbers, we employed micro-proteomics to reveal distinct global protein expression profiles of human Sertoli cells between SCOS and obstructive azoospermia (OA) with normal spermatogenesis utilizing single human Sertoli cells. We found a significant downregulation of proteins involved in cell adhesion pathways in SCOS Sertoli cells, whereas proteins related to apoptosis were markedly upregulated. Interestingly, we identified the lower expression of SPARC (secreted protein acidic and rich in cysteine) and the higher expression of FGF2 (fibroblast growth factor 2) in human Sertoli cells of the SCOS compared to normal men. SPARC silencing led to upregulation of FGF2 in human Sertoli cells, and SPARC may be associated with the occurrence of SCOS and serves as a reliable marker for the diagnosis of this disease. This study thus comprehensively offers the proteomic landscape of human Sertoli cells in the testes of SCOS patients and it sheds a novel insight into the pathogenesis of SCOS.
研究领域:
生殖生物学
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分子医学
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蛋白质组学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
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IF 8.2
Junpeng Sun,Xiaobang Liu,Jiaqun Du,Jinyu An,Yingqiao Li,Yu Hu,Shuai Cheng,Ying Xiong,Yanan Yu,He Tian,Xifan Mei,Chao Wu
In this study, manganese-doped albumin-gelatin composite nanogels (MAGN) were prepared and used to load berberine (Ber) for the treatment of gouty arthritis (GA). The nanodrug delivery system (Ber-MAGN) can target inflammatory joints due to the intrinsic high affinity of albumin for SPARC, which is overexpressed at the inflammatory site of GA. Characterization of the pharmaceutical properties in vitro showed that Ber-MAGN had good dispersion, and the particle size was 121 ± 10.7 nm. The sustained release effect significantly improved the bioavailability of berberine. In vitro and in vivo experimental results showed that Ber-MAGN has better therapeutic effects in relieving oxidative stress and suppressing inflammation. Therefore, Ber-MAGN, as a potential pharmaceutical preparation for GA, provides a new reference for the clinical treatment plan of GA.
研究领域:
药学
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纳米技术
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风湿病学
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药物递送系统
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 5.6
Zexin Li,Xiao Wang,Yuanyuan Cui,Yi Liu,Rui Wei,Yixin Wang,Xiaolong Tang,Liangbin Li,Jiasai Li,Keqiang Zuo
Hepatic ischemia–reperfusion injury (HIRI) is a complicated pathological process impacting the prognosis of patients suffering from liver resection and transplantation surgery. 2-oxoglutarate and iron dependent oxygenase domain containing 1 (OGFOD1), a crucial factor involved in protein translation, was highly expressed during HIRI. However, its role as well as underlying mechanism is still unclear. In this study, two datasets from Gene Expression Omnibus database were analyzed and we focused on OGFOD1 which is associated with ischemia–reperfusion. Later, a HIRI rat model and a hypoxia/reoxygenation (H/R) hepatocyte model were established to explore the expression of OGFOD1 and its underlying mechanism. Furthermore, transcriptomics and proteomics were performed to analyze the downstreams of OGFOD1 in H/R hepatocytes. Our results showed that the expression of OGFOD1 in HIRI rats and H/R hepatocytes were higher than negative controls. OGFOD1 silencing ameliorated liver function, reduced hepatocellular apoptosis and mitigated oxidative stress. Later, the combined analysis of transcriptomics and proteomics showed that 5811 mRNAs and 476 proteins were modulated by OGFOD1 silencing and these factors were classified into four classes. Among these factors, secreted protein acidic and rich in cysteine (SPARC) in Class III, with decreased protein level but no-changed mRNA level, caught our eyes. Silencing OGFOD1 decreased the protein level of SPARC, but not its mRNA level. More interestingly, SPARC overexpression rescued the effects of OGFOD1 silencing on apoptosis and oxidative stress in H/R hepatocytes. Totally, OGFOD1 was a vital modulator during HIRI and its downregulation alleviated oxidative stress and apoptosis through declining SPARC protein level.
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PubMed
高影响因子
BIOMATERIALS
·
2018
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IF 8.806
Yujie Zhang,Zhongyuan Guo,Zhonglian Cao,Wenxi Zhou,Yu Zhang,Qinjun Chen,Yifei Lu,Xinli Chen,Qin Guo,Chao Li,Donghui Liang,Tao Sun,Chen Jiang
Targeted delivery and accumulation of chemotherapeutics to tumor sites is in high demand and extremely challenging for anticancer therapy. Studies show that albumin is actively recruited into tumor tissue overexpressing albumin-binding proteins including secreted protein acidic and rich in cysteine (SPARC) and gp60. Herein, a novel redox-responsive paclitaxel-loaded micelle system with the modification of ABD035, which specifically and strongly binds to albumin, is designed to combine the strengths of albumin and micelles together for antitumor drug biomimetic delivery. The ABD035-modified micelle has a strong binding response to albumin and co-localization of BODIPY-labeled ABD035-modified micelle and SPARC is observed in tumor tissues. Furthermore, the ABD035-modified micelle significantly improves the therapeutic effect in the animal model bearing triple negative breast cancer by increasing drug accumulation in tumor tissue, enhancing cell uptake efficiency, rapidly releasing prototype drug under intracellular reductive conditions and increasing tumor cell apoptosis. These results together vote the biomimetic delivery of ABD035-modified micelle as a promising strategy for cancer therapy.
研究领域:
药理学
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肿瘤学
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药物递送系统
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生物医学工程
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DOI
PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 9
·5609-5618
·
IF 3.9
Wen Kang,Yuyuan Shi,Zhenlu Yang,Xindao Yin,Ying Zhao,Lixing Weng,Zhaogang Teng
As a non-invasive cancer treatment, photodynamic therapy (PDT) has great applications in superficial tumors because of its high selectivity and low cumulative toxicity. However, the poor tumor-targeting ability and short blood circulation time of conventional photosensitizers (PSs) limit the efficacy of PDT to some extent. In this study, we synthesized flexible hollow human serum albumin (HHSA) and loaded photosensitizer Chlorin e6 (Ce6) and the chemotherapeutic drug Doxorubicin (DOX) for synergistic cancer therapy. HHSA can enhance drug delivery and cellular uptake through targeting gp60 and SPARC receptors and unique flexible hollow structures. The TEM images show that HHSA possesses distinct flexible hollow structures, as well as good monodispersity and deformability. After loading Ce6 and DOX, HHSA@Ce6-DOX displays better therapeutic effects than HHSA@DOX on the growth of 4T1 breast cancers without irradiation. Remarkably, it has a significantly higher therapeutic effect (relative cell activity: 45% vs. 74%) than HHSA@Ce6 under 660 nm irradiation. Furthermore, the excellent biocompatibility of HHSA@Ce6-DOX has been proved both in vitro and in vivo, indicating that it has a promising future in synergistic tumor treatments.
研究领域:
药学
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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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DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Meng Zhang,Yiqing Ye,Zhengyun Chen,Xiaodong Wu,Yue Chen,Pengfei Zhao,Mengdan Zhao,Caihong Zheng
Endometriosis seriously affects 6–10% of reproductive women globally and poses significant clinical challenges. The process of ectopic endometrial cell colonization shares similarities with cancer, and a dysfunctional immune microenvironment, characterized by non-classically polarized macrophages, plays a critical role in the progression of endometriosis. In this study, a targeted nano delivery system (BSA@Mif NPs) was developed using bovine serum albumin (BSA) as the carrier of mifepristone. The BSA@Mif NPs were utilized to selectively target M2 macrophages highly enriched in ectopic endometrial tissue via the SPARC receptor. This targeting strategy increases drug concentration at ectopic lesions while minimizing its distribution to normal tissue, thereby reducing side effects. In vitro studies demonstrated that BSA@Mif NPs not only enhanced the cellular uptake of M2-type macrophages and ectopic endometrial cells but also improved the cytotoxic effect of mifepristone on ectopic endometrial cells. Furthermore, the BSA@Mif NPs effectively induced immunogenic cell death (ICD) in ectopic endometrial cells and repolarized M2-type macrophages toward the M1 phenotype, resulting in a synergistic inhibition of ectopic endometrial cell growth. In vivo experiments revealed that BSA@Mif NPs exhibited significant therapeutic efficacy in endometriosis-bearing mice by increasing drug accumulation in the endometriotic tissues and modulating the immune microenvironment. This targeted biomimetic delivery strategy presents a promising approach for the development of endometriosis-specific therapies based on existing drugs. Statement of Significance Macrophages play an essential role in immune dysfunctional microenvironment promoting the occurrence and progression of endometriosis and can be a crucial target for developing immune microenvironment regulation strategies for the unmet long-term management of endometriosis. The albumin nanoparticles constructed based on SPARC overexpression in macrophages and endometrial cells and albumin biosafety can achieve the targeted therapy of endometriosis by increasing the passive- and active-mediated drug accumulation in ectopic endometrium and remodeling the immune microenvironment based on macrophage regulation. This study has the following implications: i) overcoming the inherent shortcomings of clinical drugs by nanotechnology is an alternative way of developing medication; ii) developing microenvironment modulation strategies based on macrophage regulation for endometriosis management is feasible.
研究领域:
妇科学
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药学
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纳米技术
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免疫学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Lei Xu,Jiahe Hu,Xiuwei Yan,Hongtao Zhao,Mo Geng,Jiheng Zhang,Chunxiao Zhou,Zhihui Liu,Bo Li,Shaoshan Hu
Photodynamic therapy (PDT) is an effective treatment for glioblastoma (GBM) that activates photosensitizers to produce reactive oxygen species (ROS) while minimizing harm to normal tissues. However, the therapeutic outcomes of PDT are often unsatisfactory. This limitation arises partly from the challenges posed by the blood–brain barrier (BBB) in transporting photosensitizers and partly from the excessive levels of glutathione (GSH) in the tumor microenvironment (TME), which can neutralize ROS. Hypericin (HYP) has emerged as a promising photosensitizer for PDT due to its excellent photosensitizing properties and antitumor activity. Dysregulated iron metabolism is a hallmark of numerous cancers, including GBM. In this study, biodegradable tetra-sulfide-bound dendritic mesoporous organosilicas nanocomposite (NCs) modified with bovine serum albumin (BSA) were synthesized. NCs penetrates the BBB and selectively targets GBM by binding to secreted acidic protein acidic and rich in cysteine (SPARC), an albumin-binding receptor that is prominently expressed in both the BBB and GBM. Upon degradation in response to high GSH concentrations in the TME, the NCs release their payload while concurrently depleting GSH. Under laser irradiation, the ROS-generating agent HYP, loaded within the NCs, is combined with the ferroptosis inducer erastin to achieve a synergistic anti-GBM effect via PDT/ferroptosis. Additionally, the NCs induces oxeiptosis by regulating KEAP1/PGAM5/AIFM1 pathway. Consequently, NC inhibits GBM growth by inducing ferroptosis and oxeiptosis through excessive ROS production. This study demonstrates the potential of NCs to enhance the effectiveness of PDT, offering a promising therapeutic strategy for GBM patients.
研究领域:
肿瘤学
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纳米技术
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治疗学
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神经科学
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DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Zhijun Miao,Anan Xu,Gang Shen,Siyi Tang,Jie Luo,Jiajian Yang,Zhe Chen,Jinxian Pu,Tao Yang
Immunogenic cell death (ICD) induced by chemotherapeutics holds promise for cancer therapy, but limited drug penetration across the bladder mucosa and an immune-excluded tumor microenvironment (TME) have hindered success in bladder cancer. Here, we develop fluorinated albumin nanocages as transmucosal delivery vesicles that concurrently target cancer-associated fibroblasts (CAFs) and tumor cells to potentiate chemoimmunotherapy. Surface fluorination enables mucosal penetration, while recognition of secreted protein acidic and cysteine-rich (SPARC) protein ensures selective uptake by CAFs and tumor cells. Encapsulated chemotherapeutics enhance ICD through inhibition of the Bcl-2 pathway, promoting tumor cell death. Simultaneous CAF disruption reduces stromal fibrosis, facilitating anti–PD-L1 antibody delivery and T-cell infiltration. This dual-targeting strategy synergizes ICD with immune checkpoint blockade to eradicate bladder tumors by recruiting cytotoxic T cells and suppressing immunosuppressive phenotypes. Ex vivo studies in freshly resected human bladder tumors further validated the translational potential. Our findings highlight fluorinated albumin nanocages as a versatile transmucosal platform to remodel the tumor–stroma axis and amplify chemoimmunotherapy in bladder cancer.
研究领域:
肿瘤学
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纳米医学
·
免疫治疗
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药物递送
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癌症生物学
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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）