APPLIED SURFACE SCIENCE
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2022
·
IF 7.392
Mingyu You,Lei Zhang,Tobias A. Gmür,Kaihuan Zhang,Stefan Zürcher,Wen Li,Guangyin Yuan,Nicholas D. Spencer,Jia Pei
Synthetic pure hydroxyapatite (HA), though widely investigated as an artificial orthopedic implant material, has neither anti-infection properties nor innate interfacial bioactivity. Ideally, surface modification of this material needs to be developed with simultaneous anti-microbial capacity and superior cytocompatibility. Herein, graft copolymers of a PAA backbone functionalized with a high density of polyethylene glycol (PEG), and varying grafting densities of cyclic Arg-Gly-Asp-d-Phe-Cys peptides (cRGD) end-grafted onto the PEG chains have been designed and synthesized. Systematic study on the grafted anchoring groups first indicates a synergistic binding mechanism of the copolymer to HA surface, involving electrostatic interaction of the protonated amino (–NH 3 + ) with negatively charged HA, assisted with coordination bonding through the nitrodopamine (ND) group. The PEGylated graft copolymers are demonstrated to firmly adsorb to the HA surface as an ultrathin self-assembly layer from a HEPES buffer solution, showing stability with insignificant desorption and effective inhibition of non-specific protein adsorption evaluated by XPS and QCM-D assays. Direct adhesion assays confirm that HA, modified with the density-optimized cRGD/PEG-functionalized graft polymer, can considerably promote osteoblast attachment, while preventing different strains of bacteria adhesion in the initial phase.
研究领域:
材料科学
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生物医学工程
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细胞生物学
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DOI
高影响因子
DRUG DELIVERY
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2023
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IF 6
Yaqin Tu,Wei Zhang,Guorun Fan,Chenming Zou,Jie Zhang,Nan Wu,Jiahui Ding,Wen Qing Zou,Hongjun Xiao,Songwei Tan
High intracellular reactive oxygen species (ROS) level is characteristic of cancer cells and could act as a target for the efficient targeted drug delivery for cancer treatment. Consequently, biomaterials that react to excessive levels of ROS are essential for biomedical applications. In this study, a novel ROS-responsive polymer based on D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly (β-thioester) (TPGS-PBTE) was synthesized for targeted delivery of the first-line antineoplastic drug, paclitaxel (PTX). The resultant TPGS-PBTE NPs showed good ROS-responsive capability in size change and drug release. Compared to PTX, PTX-loaded nanoparticles (PTX@TPGS-PBTE NPs) showed enhanced cytotoxicity and higher level of apoptosis toward squamous cell carcinoma (SCC-7) cells. Tumor-targeted delivery of the NPs was also observed, especially after being modified with a tumor-targeting peptide, cRGD. Enhanced tumor growth inhibition was also observed in head and neck cancer SCC-7 murine models. In summary, PTX@TPGS-PBTE NPs can achieve good therapeutic effects of PTX against head and neck cancer both in vitro and in vivo, especially when modified by cRGD for active targeting, which enriched the application of ROS responsive system utilized in the delivery of anticancer drugs.
研究领域:
癌症治疗
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药学科学
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纳米技术
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生物医学工程
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Haitao Huang,Tao Yue,Ke Xu,Jafar Golzarian,Jiahui Yu,Jin Huang
Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd 3+ from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5 nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100 nm and a longitudinal relaxivity ( r 1 ) of 10.2 mM −1 S −1 . Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T 1 -weighted MRI diagnosis of tumor.
研究领域:
生物医学工程
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影像医学
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材料科学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
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IF 5.9
Ying He,Nengbin Wan,Hongwu Deng,Yi Zhang,Qiang Liu,Li Li,Hao Liu,Xiao He,Qing Zhu
Triple-negative breast cancer (TNBC) is an aggressive malignancy often characterized by chemoresistance, partly due to the overexpression of drug efflux transporters like ABCG2. To address this challenge, this study developed and evaluated a cRGD-modified, pH-sensitive liposomal system for the targeted co-delivery of docetaxel (DTX) and siRNA against ABCG2 (si-ABCG2). The synthesized nanoparticles (DTX/siRNA/cRGD-PLPs) exhibited optimal physicochemical properties, including a mean particle size of approximately 241.7 nm, efficient co-loading of DTX and siRNA, and pH-responsive cargo release, while protecting the siRNA from degradation in serum. Also, DTX/siRNA/cRGD-PLPs maintained homogeneous size distributions over the storage period and induced minimal hemoglobin release, with hemolysis rates remaining below safety threshold. These liposomes demonstrated enhanced, time-dependent uptake into TNBC cell lines HCC1937 and MDA-MB-231. In vitro , the DTX/siRNA/cRGD-PLPs formulation was significantly more effective at inhibiting cell viability, proliferation, migration, and invasion, and at inducing apoptosis, compared to the free drug combinations and other controls. Moreover, the dual-payload co-delivery liposomes (DTX/siRNA/cRGD-PLPs) exerted superior anti-tumor effects relative to single-agent formulations. In an MDA-MB-231 xenograft mouse model, the liposomal treatment was well-tolerated and resulted in marked tumor growth inhibition, which was associated with reduced cell proliferation (Ki67) and increased apoptosis (Caspase-3) within the tumor tissue. This targeted co-delivery system shows significant potential for improving TNBC treatment by synergistically enhancing therapeutic efficacy and overcoming chemoresistance.
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DOI
PubMed
高影响因子
Biomolecules
·
2022
·Vol. 12
·期 9
·1277
·
IF 6.064
Mengjun Wang,Hongliang He,Di Liu,Ming Ma,Yu Zhang
Although cerium oxide nanoparticles are attracting much attention in the biomedical field due to their unique physicochemical and biological functions, the cerium oxide nanoparticles greatly suffer from several unmet physicochemical challenges, including loss of enzymatic activity during the storage, non-specific cellular uptake, off-target toxicities, etc. Herein, in order to improve the targeting property of cerium oxide nanoparticles, we first modified cerium oxide nanoparticles (CeO2) with polyacrylic acid (PAA) and then conjugated with an endothelium-targeting peptide glycine-arginine-aspartic acid (cRGD) to construct CeO2@[email protected]The physiochemical characterization results showed that the surface modifications did not impact the intrinsic enzymatic properties of CeO2, including catalase-like (CAT) and superoxide dismutase-like (SOD) activities. Moreover, the cellular assay data showed that CeO2@[email protected]exhibited a good biocompatibility and a higher cellular uptake due to the presence of RGD targeting peptide on its surface. CeO2@[email protected]effectively scavenged reactive oxygen species (ROS) to protect cells from oxidative-stress-induced damage. Additionally, it was found that the CeO2@[email protected]converted the phenotype of macrophages from proinflammatory (M1) to anti-inflammatory (M2) phenotype, inhibiting the occurrence of inflammation. Furthermore, the CeO2@[email protected]also promoted endothelial cell-mediated migration and angiogenesis. Collectively, our results successfully demonstrate the promising application of CeO2@[email protected]in the future biomedical field.Keywords:cerium oxide nanoparticles;CeO2@PAA;CeO2@[email protected];antioxidant;anti-inflammatory;angiogenesis
研究领域:
纳米技术
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生物医学工程
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药学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2016
·Vol. 4
·期 11
·1932-1940
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IF 4.872
Jing-Jing Hu,Li-Han Liu,Ze-Yong Li,Ren-Xi Zhuo,Xian-Zheng Zhang
In this paper, we report on an intelligent mesoporous silica-based multifunctional theranostic nanoplatform (designated as MMTNP) for tumor imaging as well as controlled drug release. This theranostic nanoplatform consists of MCM-41 typical mesoporous silica nanoparticles (MSNs) as a hydrophobic drug carrier, matrix metalloprotease-2 (MMP-2) activated fluorescence imaging peptides on the surface of MSNs served as diagnostic probes as well as enzyme-responsive nanovalves blocking the pores, and cRGD peptides further functionalized on the surface of MSNs for tumor targeting. In the absence of MMP-2 conditions, the proximity between the fluorescent dye 5(6)-carboxytetramethylrhodamine hydrochloride (TAMRA) and the quencher 4,4-dimethylamino-azobenzene-4′-carboxylic acid (Dabcyl) on the surface of MSNs resulted in no fluorescence. When the drug loaded nanoplatform arrived at tumor tissue with overexpressed MMP-2, the fluorescence of TAMRA became recovered efficiently due to the hydrolysis of the MMP-2 sensitive peptide substrate, realizing tumor imaging and triggering drug release. In addition, the further introduced cRGD peptide significantly enhanced the targeting efficiency through receptor-mediated endocytosis in tumor cells.
研究领域:
生物医学工程
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Yu Yang,Jiang Du,Jingjing Gan,Xiang Song,Jiaxin Shu,Chaoli An,Li Lu,Hui Wei,Junyi Che,Xiaozhi Zhao
Reactive oxygen species (ROS) scavenging of nanozymes toward acute kidney injury (AKI) is a current promising strategy, however, the glomerular filtration barrier (GFB) limits their application for treating kidney related diseases. Here, a neutrophil-mediated delivery system able to hijack neutrophil to transport nanozyme-loaded cRGD-liposomes to inflamed kidney for AKI treatment by cRGD targeting integrin αvβ1 is reported. The neutrophil-mediated nanozyme delivery system demonstrated great antioxidant and anti-apoptosis ability in HK-2 and NRK-52E cell lines. Moreover, in ischemia-reperfusion (I/R) induced AKI mice, a single dose of LM@cRGD-LPs 12 h post-ischemia significantly reduces renal function indicators, alleviates renal pathological changes, and inhibits apoptosis of renal tubular cells and the expression of renal tubular injured marker, thus remarkably reducing the damage of AKI. Mechanistically, the treatment of LM@cRGD-LPs markedly inhibits the process of Nrf2 to the nucleus and reduces the expression of the downstream HO-1, achieves a 99.51% increase in renal tissue Nrf2 levels, and an 86.31% decrease in HO-1 levels after LM@cRGD-LPs treatment. In short, the strategy of neutrophil-mediated nanozyme delivery system hold great promise as a potential therapy for AKI or other inflammatory diseases.
研究领域:
肾病学
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药学
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生物技术
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分子生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2026
·
IF 6.7
Qiu-Ya Ji,Ran Meng,Si-Jie Wu,Ran Feng,Bao Zhang
Abstract Exosomes derived from probiotics are emerging as innovative oral nanocarriers but face challenges in targeted delivery and stability. Here, Lactobacillus helveticus-derived exosomes (LHexo) were dual-functionalized with mannose and cRGD (McRLHexo), yielding improved membrane lipid ordering, denser PEG brush layer, and distinct “cloud-like” surface nanostructure. McRLHexo exhibited enhanced stability under UV (transmittance reduction > 98%), thermal, and digestive conditions (drug retention >86%), and increased pterostilbene (PTS) loading. Functionally, McRLHexo@PTS achieved efficient epithelial translocation via cRGD-integrin pathways and macrophage targeting via Man/cRGD dual-recognition. In DSS-induced colitis mice, McRLHexo showed optimal targeting accumulation and uptake in the colon. Importantly, McRLHexo@PTS markedly alleviated colitis, restoring body weight, colon length, and epithelial integrity while reducing inflammatory cytokines and oxidative stress and enhancing antioxidant defenses. This study establishes a dual-targeted probiotic exosome platform for oral therapy and provides insights into ligand-membrane engineering for precision intestinal delivery.
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DOI
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Yanrui Liang,Weihong Guo,Chuangji Li,Guodong Shen,Haoxian Tan,Peiwen Sun,Zhian Chen,Huilin Huang,Zhenhao Li,Zhenyuan Li,Yingxin Ren,Guoxin Li,Yanfeng Hu
/Gd(NH2)2 (cRGD-PPIG) NPs were tested for their biosafety and metastatic LN mapping ability. They were drained specifically into LNs and selectively taken up by gastric MKN45 cells via αvβ 3 integrin-mediated endocytosis.Results: This phenomenon enabled MR/optical/near-infrared fluorescence multimodal metastatic LN mapping, guiding the creation of accurate and highly efficient PTT for gastric cancer metastatic LNs in mice.Conclusion: In summary, we fabricated tumor-targeted cRGD-PPIG NPs with MR/optical/near-infrared fluorescence multimodal metastatic LN mapping capacity for surgery and efficient PTT guidance post-surgery.
研究领域:
纳米技术
·
癌症研究
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医学影像
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诊疗一体化
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2026
·
IF 8.7
Zhibo Gu,Hua Zhu,Yong Zhang,Jie Jiang,Donghua Gu,Jiangang Chen
Objective This study developed a multifunctional MnFe2O4/TiVNbMoC3-cRGD (MXenes) nanocomposite for targeted photothermal- photodynamic therapy against bladder cancer.Methods A multifunctional MXene-based nanocomposite was constructed by integrating MnFe2O4 nanoparticles onto TiVNbMoC3 MXene nanosheets to form a layer-on-layer Schottky junction, followed by conjugation of cRGD peptides for tumor targeting. Successful synthesis, colloidal stability, broad optical absorption, efficient photothermal conversion and ROS generation under 808 nm laser were confirmed. In vitro assays were conducted using 5637 bladder cancer cells, and a murine bladder tumor model was established to evaluate the anticancer efficacy. Biocompatibility assessments were also carried out.Results The composite was constructed by integrating MnFe2O4 nanoparticles onto TiVNbMoC3 MXene nanosheets, which formed a layer - on - layer Schottky junction. Then, cRGD peptides were conjugated to the surface for tumor targeting. Comprehensive characterization confirmed successful synthesis, favorable colloidal stability, broad optical absorption, and efficient photothermal conversion and reactive oxygen species (ROS) generation under 808 nm laser irradiation. In vitro, the cRGD-targeted nanocomposite was efficiently internalized by 5637 bladder cancer cells and showed significantly higher anticancer efficacy than doxorubicin (DOX), including inhibition of proliferation, migration, colony formation, and induction of apoptosis and immunogenic cell death. In a murine bladder tumor model, the nanocomposite achieved the strongest tumor growth suppression and reduced final tumor volume more effectively than DOX. Biocompatibility assessments showed minimal hemolysis and no major organ damage at therapeutic doses.Conclusion This MXene-based Schottky junction nanocomposite represents a promising targeted platform for dual-modal photothermal/photodynamic therapy combined with immune activation in bladder cancer, warranting further translational investigation.
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2026
·
IF 8.7
Jing Zhang,Xiaoqiang Kong,Xiangping Wu,Dongyun Tao,Xiang Li,Huimin Cheng
Introduction Triple-negative breast cancer (TNBC) is an aggressive malignancy with poor prognosis, and Fusobacterium nucleatum (Fn) colonization further aggravates tumor progression, immunosuppression and therapeutic resistance. Conventional monotherapies are limited by insufficient tumor targeting, rapid drug clearance and failure to reverse immune suppression. Here, we fabricated cRGD-modified nanoparticles (Ag@GQDs/QUE-siP-c-L) for co-delivery of AgNPs, quercetin (QUE) and PD-L1 siRNA (siP).Methods The morphology, particle size, surface metal elements, drug content and QUE entrapment efficiency of Ag@GQDs/QUE-siP-c-L were obtained using particle size analysis, SEM, inductively coupled plasma-optical emission spectrometry (ICP-OES) and HPLC. We further detected cellular uptake, in vitro drug release, cytotoxicity, intracellular reactive oxygen species level, PD-L1 gene silencing efficiency and in vitro anti-Fn activity. Pharmacokinetics and tissue distribution of Ag and QUE were analyzed by ICP-OES and LC-MS/MS, and in vivo antitumor efficacy and biosafety were tested in Fn-colonized orthotopic 4T1 tumor mice.Results Ag@GQDs/QUE-siP-c-L exhibited uniform spherical morphology (195.87± 15.96 nm) with high encapsulation of QUE. cRGD modification enhanced Ag/QUE cellular uptake in 4T1 cells, with pH-responsive release accelerated under tumor acidic conditions. The nanoparticles exhibited selective tumor cytotoxicity, induced oxidative stress, downregulated PD-L1 mRNA, and exerted potent anti-Fn activity in vitro. Pharmacokinetics revealed increased AUC0-t and reduced clearance compared with free drugs, and cRGD modification promoted tumor accumulation and retention of drugs. In vivo preliminary experiments proved the Ag@GQDs/QUE-siP-c-L formulation suppressed tumor growth with a tumor inhibition rate of 45%, and effectively modulated the tumor immune microenvironment: it increased tumor-infiltrating CD3⁺CD4⁺ T cells, reduced PD-L1⁺CD11c⁺ dendritic cells, and decreased the proportions of immunosuppressive Tregs and MDSCs. Hematoxylin-eosin staining and serum liver-kidney biochemistry confirmed no obvious systemic toxicity.Conclusion Ag@GQDs/QUE-siP-c-L serves as a multimodal nanoplatform for Fn-associated TNBC with combined in vitro antibacterial, gene silencing and in vivo antitumor immunomodulatory effects, showing great potential for future translational research.
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Jianbin Mo,Lizhen He,Bin Ma,Tianfeng Chen
The blood–brain barrier (BBB) is the main bottleneck to prevent some macromolecular substance entering the cerebral circulation, resulting the failure of chemotherapy in the treatment of glioma. Cancer nanotechnology displays potent applications in glioma therapy owing to their penetration across BBB and accumulation into the tumor core. In this study, we have tailored the particle size of mesoporous silica nanoparticles (MSNs) through controlling the hydrolysis rate and polycondensation degree of reactants, and optimized the nanosystem that could effectively penetrate BBB and target the tumor tissue to achieve enhanced antiglioma efficacy. The nanoparticle was conjugated with cRGD peptide to enhance its cancer targeting effect, and then used to load antineoplastic doxorubicin. Therefore, the functionalized nanosystem (DOX@MSNs) selectively recognizes and binds to the U87 cells with higher expression level of ανβ3 integrin, sequentially enhancing the cellular uptake and inhibition to giloma cells, especially the particle size at 40 nm. This particle could rapidly enter cancer cells and was difficult to excrete outside the cells, thus leading to high drug accumulation. Furthermore, DOX@MSNs exhibited much higher selectivity and anticancer activity than free DOX and induced the glioma cells apoptosis through triggering ROS overproduction. Interestingly, DOX@MSNs at about 40 nm exhibited stronger permeability across the BBB, and could disrupt the VM-capability of glioma cells by regulating the expression of E-cadherin, FAK, and MMP-2, thus achieving satisfactory antiglioblastoma efficacy and avoiding the unwanted toxic side effects to normal brain tissue. Taken together, these results suggest that tailoring the particle size of MSNs nanosystem could be an effective strategy to antagonize glioblastoma and overcome BBB.
研究领域:
纳米医学
·
肿瘤学
·
药理学
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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）