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POLYMER BULLETIN · 2021 ·Vol. 79 ·期 4 ·2173-2188 · IF 2.87

Preparation and evaluation of PLA/PVP core–shell microparticles mat via single capillary electrospraying as a potential drug-loading material

Hou Jiazi,Zhou Guibin,Hu Jinlun,Wang Yihuan,Gao Shuang

Microparticles had attracted a lot of attention for biomedical applications because of their injectable and biomimetic properties. We reported a method for preparing Polylactic acid (PLA)/Polyvinylpyrrolidone (PVP) core–shell microparticles by single capillary electrospraying and explored their potential applications for drug-loading. The shape of microparticles can be controlled by varying ratios of PLA and PVP during the electrospraying process. Different morphologies were achieved including spindle-like, erythrocyte-like and disk-like microparticles. Furthermore, the method of preparing core–shell microparticles was simple and repeatable. Compared with spherical microparticles, erythrocyte-like microparticles can flow through capillaries by morphing into a parachute-like shape. When the particle morphology converted to disk-like, the increase of water contact angle attributed to the PVP rapid dissolution and the residual PLA interconnection to form a continuous hydrophobic membrane. Besides, the microparticle membrane was extremely low-toxic to cells by MTT assay. Taken together, we prepared injected core–shell microparticles by single capillary electrospraying, which had potential application in drug-loading.

研究领域: 生物医学工程 · 材料科学 · 药剂学
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ANNALS OF BIOMEDICAL ENGINEERING · 2022 ·Vol. 50 ·期 12 ·1826-1836 · IF 4.219

Ultrasound-Triggered On-Demand Insulin Release for Diabetes Mellitus Treatment

Bao Hongyi,Chen Jingru,Wang Xiaoping,Chen Chao,Gong Jun,Liu Jun,Xia Donglin

Exogenous insulin (INS) is successfully used for controlling glucose in diabetic patients. Although frequent INS injections can overcome hyperglycemia, they are both painful and inconvenient. Herein, we report an ultrasound-regulated INS release platform (INS-PPIX@ER hydrogel) that allows for remotely regulated on-demand INS release and minimizes pain. In this system, protoporphyrin IX (PPIX)-containing erythrocytes (ERs) served as an INS reservoir, an injectable peptide hydrogel provided strong protection for the ERs, and INS release was regulated using ultrasound. This particular INS release behavior was triggered by increased production of reactive oxygen species (ROS) by PPIX from the PPIX-loaded ERs under ultrasound irradiation. The ROS then interacted with the phospholipid bilayer of the ERs, thereby opening the stomata of the INS-PPIX@ER and releasing INS. INS-PPIX@ER hydrogels could control hyperglycemia within 2 h and maintained normal blood glucose levels for up to 3 days. This effective remote approach allowed closed-loop drug release spatiotemporally without causing any pain and injury. Our findings could serve as a powerful tool for constructing a precisely controlled release system.

研究领域: 生物医学工程 · 药学 · 糖尿病研究
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF MOLECULAR STRUCTURE · 2023 · IF 3.8

Investigative on the molecular mechanism of novel antioxidation peptides by 3D-QSAR, in vitro assay and MD simulations

Hongmei Li,Guimei Lin,Zhen Liang,Ying Li,Rong Zhang

Three novel antioxidant peptides MHW, YHW and FHW were designed by the analysis of 3D-QSAR. Two accurate CoMFA ( Q 2  = 0.886 and R 2  = 0.988) and CoMSIA ( Q 2  = 0.737 and R 2  = 0.955) models were established. The FTC assay showed that activities of the new peptides on lipid peroxidation is significantly better than that of the template molecule LHW. The results of erythrocyte hemolysis assay demonstrated that MHW, YHW and FHW significantly inhibited AAPH-induced erythrocyte hemolysis by scavenging free radicals at the cellular level. It caused the restoration of intracellular antioxidant enzyme (GSH, CAT and SOD) activities at an acceptable pace and the silencing of intracellular MDA formation. Furthermore, MTT toxicity assay showed that the novel antioxidant peptides had good biocompatibility and no cytotoxicity. Molecular docking and molecular dynamics simulations were used to investigate the molecular mechanism. The results showed that Ser363, Arg380, Asn414 and Arg415 residues played key roles in the antioxidant activity of MHW, YHW and FHW. And they mainly binded to the important residues of Keap1 protein stably by electrostatic force, van der Waals force, H-bonds and hydrophobic interactions, which can better fit the Kelch pocket structural domain of Keap1. Therefore, MHW, YHW and FHW had strong potential to interfere with Keap1-Nrf2 interaction and promoted the enzymatic expression of Nrf2-ARE downstream target pathway.

CAS / MDL: 1762-95-4 64-17-5
研究领域: 生物化学 · 药物化学 · 分子生物学
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ACS Applied Bio Materials · 2024 · IF 4.6

Erythrocyte-Like Mesoporous PDA@CeO2 Nanozyme with Dual Drugs for Periodontitis Treatment

Lingyu Zhang,Ying Gao,Zhuoran Wang,Yanqiu Qi,Lu Li,Tingting Wang,Daowei Li,Chungang Wang

Periodontitis is a chronic oral inflammatory disease with the characteristic of excess oxidative stress in the inflammatory site, dramatically decreasing the quality of life. Studies show that nanozymes can be ideal candidates for ROS scavenging in periodontitis. Here, we design a multipath anti-inflammatory mesoporous polydopamine@cerium oxide nanobowl (mPDA@CeO2 NB) with multienzyme mimicking properties, which combines the advantages of both CeO2 NP and mPDA NB for synergistically eliminating reactive oxygen species (ROS), including hydroxyl radical (•OH), hydrogen peroxide (H2O2), and superoxide (O2•–). Besides, the erythrocyte-like structure of mNBs makes them a facility for cell uptake, and the mesopores can load both hydrophobic and hydrophilic drugs for combined anti-inflammatory therapy. In vitro and in vivo experiments prove that the combination of CeO2 and mPDA can synergistically achieve multiple complementary ROS eliminations and suppression of ROS-induced inflammation. Moreover, the ROS regulation plus anti-inflammatory drugs in one mPDA@CeO2 NB prevents the progression of periodontitis in a mouse model. Therefore, the design of mPDA@CeO2 NB with these excellent properties provides a therapeutic strategy for inflammatory diseases.

CAS / MDL: 657-24-9
研究领域: 牙科学 · 纳米技术 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Medicine · 2021 · IF 5.093

18F-PEG1-Vinyl Sulfone-Labeled Red Blood Cells as Positron Emission Tomography Agent to Image Intra-Abdominal Bleeding

Zhang Xinyi,Wang Li,Fu Wenhui,Feng Yue,Zeng Chengrun,Zhou Liu,Zhang Tao,Xu Tingting,Cao Jianpeng,Li Zibo,Chen Yue

18F-Labeled blood pool agents (BPAs) have attracted great attention for identifying bleeding sites. However, many BPAs are not sufficiently evaluated partially due to the limitations of labeling methods. In our previous work, we noticed that 18F-PEG1-vinyl sulfone (18F-VS) could efficiently label red blood cells (RBCs) ex vivo and in situ. However, its application as BPA is not fully evaluated. In this study, we systematically explored the feasibility of using 18F-VS-labeled RBCs as a positron emission tomography (PET) BPA for intra-abdominal bleeding diagnosis. In brief, we first optimized the labeling conditions, which lead to an 80% labeling yield of RBCs after incubating with 18F-VS in phosphate-buffered saline (PBS) at 37°C for 20 min. 18F-VS-labeled RBCs were found to be stable in vitro, which could simplify its transportation/storage for in vivo applications. In normal rat PET study, the cardiovascular system could be clearly imaged up to 5 h post injection (p.i.). An intra-abdominal hemorrhage rat model demonstrated that the 18F-VS-labeled RBCs clearly showed the dynamic changes of extravascular radioactivity due to intra-abdominal hemorrhage. Validation in the model of gastrointestinal bleeding clearly demonstrated the great potential of using 18F-VS-labeled RBCs as a BPA, which could be further evaluated in future studies.

研究领域: 医学影像学 · 核医学 · 放射化学
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL IMMUNOPHARMACOLOGY · 2025 · IF 4.7

Identification of RBM3 as a novel regulator of human fetal hemoglobin expression

Shuangping Ma,Xianting Liu,Yiran Qin,Yilong Wang,Yu Feng,Binfeng Cheng,Lei Wang

Sickle cell disease (SCD) and β-thalassemia are autosomal recessive genetic disorders caused by abnormal synthesis of β-globin chains. Reversing the transition of fetal-to-adult hemoglobin after birth shows great potential in the treatment of these disorders. Here, we identified an RNA-binding protein, RBM3, as a novel HbF (HbF, α 2 γ 2 ) suppressor. Specifically, downregulation of RBM3 in the erythroid progenitor cell line HUDEP-2 robustly induced γ-globin expression at both the mRNA and protein levels, with a slight impact on β-globin levels. Conversely, overexpression of RBM3 in HUDEP-2 cells led to a marked reduction in γ-globin expression. According to the previous study, we introduced specific inhibitors targeting FAK and Src to block RBM3 protein synthesis. Surprisingly, treatment with the FAK inhibitor resulted in a significant increase in γ-globin expression, whereas the Src inhibitor had little effect. Mechanistically, RBM3 depletion accelerated the degradation of BCL11A protein at the post-transcriptional level, without affecting its mRNA stability. Moreover, RBM3 silencing restricted the overall translation efficiency while selectively lifting the ratio of γ-globin mRNA in polysomes. Importantly, downregulation of RBM3 did not impair erythropoiesis progression, suggesting a safe and effective therapeutic strategy for SCD and β-thalassemia. Our findings identify RBM3 as a negative regulator of HbF expression and reveal it as a novel molecular target for modulating the fetal-to-adult hemoglobin switch, holding great promise for the treatment of SCD and β-thalassemia.

CAS / MDL: 9041-08-1
✓ 已验证 产品关联 DOI PubMed 高影响因子
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NEUROTOXICOLOGY · 2024 · IF 3.4

Manganese accumulation in red blood cells as a biomarker of manganese exposure and neurotoxicity

Xuedan Deng,Yonghua Guo,Xiaofei Jin,Huifang Si,Kai Dai,Meng Deng,Jing He,Changfu Hao,Wu Yao

Although overexposure to manganese (Mn) is known to cause neurotoxic damage, effective exposure markers for assessing Mn loading in Mn-exposed workers are lacking. Here, we construct a Mn-exposed rat model to perform correlation analysis between Mn-induced neurological damage and Mn levels in various biological samples. We combine this analysis with epidemiological investigation to assess whether Mn concentrations in red blood cells (MnRBCs) and urine (MnU) can be used as valid exposure markers. The results show that Mn exposure resulted in neurotoxic damage in rats and that MnRBCs correlated well with neurological damage, showing potential as a novel Mn exposure biomarker. These findings provide a basis for health monitoring of Mn-exposed workers and the development of more appropriate biological exposure limits.

CAS / MDL: 13446-34-9
研究领域: 毒理学 · 神经科学 · 职业健康
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Multifunctional magnetic MOF under cover of erythrocytes for ROS scavenging and magnetic hyperthermia thrombolysis

Pengpeng Guan,Caijie Yuan,Jiali Li,Zhou Wen,Enling Hu,Guangqian Lan,Bowen Cheng,Yinggui Huang,Fei Lu

The inadequacy of current antithrombotic therapies lies in the limited efficacy of pharmacotherapy and the poor targetability of drugs to thrombotic sites. To address these challenges, we developed a multifunctional nanoplatform, Fe 3 O 4 @MC-DEA-PBAP (FMDP), which integrates magnetic responsiveness and erythrocyte targeting for magnetic hyperthermia thrombolysis (MHT). FMDP is constructed using metal–organic frameworks (MOFs) crosslinking CaCO 3 /cyclodextrin as the base carrier, modified with 2-(Diethylamino)ethyl methacrylate (DEA) and 4-hydroxyphenylboronic acid pinacol ester (PBAP), then conjugated with nano-ferric oxide for MHT. DEA and PBAP make FMDP to adhere onto erythrocytes and scavenge reactive oxygen species (ROS), respectively. In vitro experiments proved that FMDP exhibits high photothermal conversion efficiency and robust magnetic responsiveness, enabling the thrombolytic efficiency of FMDP was three times that of uPA group. In addition, FMDP adhere to erythrocytes (83.5 %) and reach the thrombi under the cover of erythrocytes for MHT. In addition, FMDP effectively scavenges ROS, mitigating endothelial damages and promoting vascular regeneration. Overall, FMDP represents a promising therapeutic strategy for the comprehensive management of thrombosis, offering improved efficacy and reduced bleeding risks compared to conventional thrombolytic therapies.

研究领域: 生物医学工程 · 药剂学 · 材料科学
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Evidence-based Complementary and Alternative Medicine · 2019 · IF 1.984

Protective Effect and Mechanisms of New Gelatin on Chemotherapy-Induced Hematopoietic Injury Zebrafish Model

Liwen Han,Haotian Kong,Fasheng Liu,Xiaobin Li,Shanshan Zhang,Xuanming Zhang,Yong Wu,Hua Yang,Aiping Zhang,Kechun Liu

The aim of the study is to explore the protective effect of new gelatin (NG, Xin’ejiao in China) on hematopoietic injury caused by chemotherapy. Zebrafish, at 48 hours post fertilization (hpf), was treated with different chemotherapeutic drugs to establish the zebrafish hematopoietic damage model with reduced thrombocytes and erythrocytes. The protecting effects of NG on the thrombocytes and erythrocytes were observed, respectively, on zebrafish models. Then, the RT-PCR method was used to detect the change of mRNA level of the hematopoiesis-related cytokines scl1, c-myb, pu.1, GATA1, and runx1 genes. The results showed that 50 μg·mL−1 and 100 μg·mL−1 NG rescued and increased the thrombocytes numbers induced by vinorelbine (NVB) and chloramphenicol (CHL) and the erythrocytes numbers induced by methotrexate (MTX), doxorubicin (ADM), and mechlorethamine hydrochloride (MH) in zebrafish models. Meanwhile, the mRNA expression of scl1, c-myb, and GATA1 genes in the NG treatment group was raised compared with the MTX treatment group. Also, the mRNA expression of pu.1 and Runx1 in the NG treatment group was reduced compared with the MTX treatment group. In consequence, traditional Chinese medicine NG showed a certain degree protective effect on hematopoiesis injury induced by chemotherapy in this study, which may depend on the promotion of erythrocytes proliferation and the regulation of the hematopoietic genes level.

CAS / MDL: 55-86-7
研究领域: 药理学 · 血液学 · 分子生物学 · 斑马鱼研究
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Small · 2018 ·Vol. 14 ·期 38 ·1801754 · IF 9.598

Light-Triggered Biomimetic Nanoerythrocyte for Tumor-Targeted Lung Metastatic Combination Therapy of Malignant Melanoma

Wen Liu,Miaoliang Ruan,Yanming Wang,Rongguang Song,Xin Ji,Jiake Xu,Jian Dai,Wei Xue

Red blood cell (RBC) membrane-cloaked nanoparticles, reserving the intact cell membrane structure and membrane protein, can gain excellent cell-specific functions such as long blood circulation and immune escape, providing a promising therapy nanoplatform for drug delivery. Herein, a novel RBC membrane biomimetic combination therapeutic system with tumor targeting ability is constructed by embedding bovine serum albumin (BSA) encapsulated with 1,2-diaminocyclohexane-platinum (II) (DACHPt) and indocyanine green (ICG) in the targeting peptide-modified erythrocyte membrane (R-RBC@BPtI) for enhancing tumor internalization and synergetic chemophototherapy. R-RBC@BPtI displays excellent stability and high encapsulation efficiency with multiple cores enveloped in the membrane. Benefited from the stealth functionality and targeting modification of erythrocyte membranes, R-RBC@BPtI can significantly promote tumor targeting and cellular uptake. Under the near-infrared laser stimuli, R-RBC@BPtI presents remarkable instability by singlet oxygen and heat-mediated cleavage so as to trigger effective drug release, thereby achieving deep penetration and accumulation of DACHPt and ROS in the tumor site. Consequently, R-RBC@BPtI with tumor-specific targeting ability accomplishes remarkable ablation of tumors and suppressed lung metastasis in vivo by photothermal and chemotherapy combined ablation under phototriggering. This research provides a novel strategy of targeted biomimetic nanoplatforms for combined cancer chemotherapy–phototherapy.

研究领域: 生物医学工程 · 癌症治疗 · 纳米医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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International Journal of Nanomedicine · 2019 · IF 4.471

Arsenic sulfide nanoformulation induces erythroid differentiation in chronic myeloid leukemia cells through degradation of BCR-ABL

Tao Wang,Tao Wen,Hongmin Li,Bing Han,Suisui Hao,Chuan Wang,Qiang Ma,Jie Meng,Jian Liu,Haiyan Xu

Background Chronic myeloid leukemia (CML) is a myeloproliferative disorder due to the existence of BCR-ABL fusion protein that allows the cells to keep proliferating uncontrollably. Although tyrosine kinase inhibitors can inhibit the activity of BCR-ABL fusion protein to trigger the cells apoptosis, drug resistance or intolerance exists in part of CML patients. Arsenic sulfide in its raw form (r-As 4 S 4 ) can be orally administrated and certain therapeutic effects have been found out in the treatment of hematologic malignancies through inducing cell apoptosis. Methods In this work, a water-dissolvable arsenic sulfide nanoformualtion (ee-As 4 S 4 ) composed of As 4 S 4 particulates with 470 nm in diameter and encapsulated by a kind of hydrophilic polymer was fabricated and applied to the CML cell line K562, K562/AO2 and primary cells from the bone marrow of CML patients. Results Results showed that instead of inhibiting the activity of BCR-ABL, ee-As 4 S 4 induced direct degradation of BCR-ABL in K562 cells within 6 hr incubation, followed by the occurrence of erythroid differentiation in K562 after 72 hr incubation, evidenced by the significantly upregulated CD235a and benzidine staining, which was not detectable with r-As 4 S 4 . The ee-As 4 S 4 -induced erythroid differentiation was also observed in K562/AO2 cells and bone marrow mononuclear cells of CML patients. Mechanistic studies indicated that ee-As 4 S 4 induced autophagy by downregulating the level of intracellular ROS and hypoxia-inducible factor-1α significantly, which led to the subsequent degradation of BCR-ABL. When the concentration was increased, ee-As 4 S 4 induced much more significant apoptosis and cell cycle arrest than r-As 4 S 4 , and the cytotoxicity of the former was about 178 times of the latter. Conclusion ee-As 4 S 4 was capable of inducing significant erythroid differentiation of CML cells by inducing the direct degradation of BCR-ABL; the new effect could improve hematopoietic function of CML patients as well as inhibit the leukemic cell proliferation.

CAS / MDL: 92-87-5 7722-84-1
研究领域: 肿瘤学 · 血液学 · 药学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2014 ·Vol. 181 ·期 11 ·1215-1221 · IF 3.719

Direct electron transfer from native human hemoglobin using a glassy carbon electrode modified with chitosan and a poly(N,N-diethylacrylamide) hydrogel containing red blood cells

Pan Zhong-Qin,Xie Jing,Liu Xiao-Jun,Bao Ning,Gu Hai-Ying

We report on a new whole cell biosensor for hydrogen peroxide. A chitosan-coated glassy carbon electrode (GCE) was modified with poly(N,N-diethylacrylamide) (PDEA) hydrogel containing human red blood cells (RBCs). The morphology of RBCs in the hydrogel was investigated using scanning electron microscopy (SEM). Fourier transform infrared spectroscopy and SEM were applied to study the association of the PDEA chains and RBCs. Uncompromised bioactivity of native human hemoglobin in the RBCs on the modified GCE was confirmed by cyclic voltammetry. The modified electrode showed a faster electron transfer rate and better electrocatalytic activity in the reduction of H 2 O 2 than previously reported sensors. A linear relationship is found between the response to H 2 O 2 and its concentration in the range from 0.11 μM to 12.7 mM. The detection limit is 55 nM at an SNR of 3. It is assumed that the improvement of the biosensor results from the porosity and conductivity of the PDEA hydrogel. With the presence of poly(N,N-diethylacrylamide) chains, our novel red blood cells based biosensor displays a fast electron transfer rate and excellent electrocatalytic activity to H 2 O 2 . It responds to H 2 O 2 in the concentration range from 0.11 μM to 12.7 mM, and the detection limit is 55 nM (at an SNR of 3).

研究领域: 生物化学 · 生物传感技术 · 材料科学
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