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Theranostics · 2016 · IF 8.854

Novel Cs-Based Upconversion Nanoparticles as Dual-Modal CT and UCL Imaging Agents for Chemo-Photothermal Synergistic Therapy

Yuxin Liu,Luoyuan Li,Quanwei Guo,Lu Wang,Dongdong Liu,Ziwei Wei,Jing Zhou

Lanthanide-based contrast agents have attracted increasing attention for their unique properties and potential applications in cancer theranostics. To date, many of these agents have been studied extensively in cells and small animal models. However, performance of these theranostic nanoparticles requires further improvement. In this study, a novel CsLu 2 F 7 :Yb,Er,Tm-based visual therapeutic platform was developed for imaging-guided synergistic cancer therapy. Due to the presence of the heavy alkali metal Cesium (Cs) in host lattice, the nanoplatform can provide a higher resolution X-ray CT imaging than many other reported lanthanide-based CT contrast agents. Furthermore, by using the targeted RGD motif, chemotherapy drug alpha-tocopheryl succinate ( α -TOS), and photothermal coupling agent ICG, this nanoplatform simultaneously provides multifunctional imaging and targeted synergistic therapy. To demonstrate the theranostic performance of this novel nanoplatform in vivo , visual diagnosis in the small animal model was realized by UCL/CT imaging which was further integrated with targeted chemo-photothermal synergistic therapy. These results provided evidence for the successful construction of a novel lanthanide-based nanoplatform coupled with multimodal imaging diagnosis and potential application in synergistic cancer theranostics.

CAS / MDL: 25952-53-8
研究领域: 生物医学工程 · 分子影像学 · 癌症治疗
✓ 已验证 产品关联 DOI PubMed 高影响因子
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NANOTECHNOLOGY · 2025 ·Vol. 36 ·期 30 ·305101 · IF 2.8

Enhanced ferroptosis by light-triggered biomimetic nano-erythrocyte membranes for tumor synergistic therapy

Gaojian Liu,Wenjing Wen,Xuan Zhao,Yanan Jing,Hao Li,Xulong Fan,ZiXuan Huang,Gaofeng Liang

Breast cancer is the most prevalent fatal cancer among women worldwide and the leading cause of death for women. Ferroptosis is a form of programmed cell death that relies on iron and is non-apoptotic, triggered by the inhibition of the cellular antioxidant system. Photodynamic therapy (PDT) employs photosensitizers to produce reactive oxygen species (ROS), increasing oxidative stress in tumor cells. When combined with ferroptosis, PDT can work synergistically to regulate intracellular redox balance. In this study, we designed engineered nano-erythrocyte membranes for targeted delivery of Chlorin e6 (Ce6) and cisplatin (DDP) to enhance breast cancer treatment. By using mild ultrasound, Ce6 and DDP were co-loaded onto the nano-erythrocyte membranes, combining ferroptosis inducers and photosensitizers to combat breast cancer. To improve targeting capability towards breast cancer, RGD cyclic peptides were modified onto the nano-erythrocyte membranes through a thiol–maleimide coupling reaction. The RGD-modified nano-erythrocyte membranes co-loaded with Ce6 and DDP not only inherited the good stability and significant biocompatibility of red blood cell membranes but also promoted the uptake by breast cancer cells, effectively inducing ferroptosis in these cells. In conclusion, this multifunctional ‘natural’ nanodrug delivery system provides an effective and safe method for PDT combined with ferroptosis for breast cancer treatment.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Bio Materials · 2019 · IF 0

Self-Assembling Peptide Artificial Enzyme as an Efficient Detection Prober and Inhibitor for Cancer Cells

Meiling Lian,Shuo Zhang,Jun Chen,Xuejiao Liu,Xu Chen,Wensheng Yang

A new hybrid nanoparticle (NP; fluorenylmethoxycarbonyl-arginine-glycine-aspartate and hemin, Fmoc-RGD/hemin NP) was developed for the simultaneous detection and inhibition of breast cancer cells. Hemin can regulate the reactive oxygen species (ROS), while Fmoc-RGD acts as a scaffold for hemin nanocrystallization. Fmoc groups interact with the porphyrin groups of hemin through hydrophobic and π–π interactions to form a hydrophobic core of the NPs. The hydrophilic RGD chains surround the core to maintain the stability of the nanoparticles in an aqueous medium. The RGD groups of Fmoc-RGD are also selective for tumor cells. This interaction can be exploited to enhance the selectivity of tumor detection. Based on enhanced peroxidase activity, Fmoc-RGD/hemin NPs were developed as signal transducers in a facile and fast point-of-care cancer diagnosis platform. This platform is sensitive to breast cancer cells and hydrogen peroxide (H2O2), a biomarker for breast cancer. In addition, these Fmoc-RGD/hemin NPs can be used as nanoscavengers for ROS and for regulating the redox status of cancer cells. They also exhibit a targeted inhibitory effect on the epithelial–mesenchymal transition (EMT). The peptide-tuned self-assembly of Fmoc-RGD/hemin NPs as functional artificial enzymes boasts simple preparation, biofriendliness, and the versatility required for on-demand therapeutics and diagnostics for metastatic cancer cells. These NPs can therefore be used as effective tools for potential applications in medicine and biotechnology.

CAS / MDL: 67-68-5 920-66-1
研究领域: 生物化学 · 纳米医学 · 癌症研究
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Acta Biomaterialia · 2018 · IF 6.383

RGD/TAT-functionalized chitosan-graft-PEI-PEG gene nanovector for sustained delivery of NT-3 for potential application in neural regeneration

Dongni Wu,Yongnu Zhang,Xiaoting Xu,Ting Guo,Deming Xie,Rong Zhu,Shengfeng Chen,Seeram Ramakrishna,Liumin He

In this study, we prepared a multifunctional gene delivery nanovector containing a chitosan (CS) backbone and polyethylenimine (PEI) arms with arginine-glycine-aspartate (RGD)/twin-arginine translocation (TAT) conjugated via polyethylene glycol (PEG). Branched PEI, with a molecular weight of 2000 Da, was used to achieve a balance between biocompatibility and transfection efficiency, whereas RGD/TAT peptides were conjugated for enhanced targeting ability and cellular uptake. Synthesis of the copolymers was confirmed by characterizing the chemical structure with 1 H nuclear magnetic resonance and Fourier Transform Infrared Spectroscopy (FTIR). The nanovector was biocompatible with cells and showed excellent capability for DNA condensation ; the resulting complexes with DNA were well-formed, and possessed small particle size and reasonable positive charge. Higher gene transfection efficiency, compared to that achieved with PEI (25 kDa), was confirmed in tumor (HeLa cells) and normal cells (293T and NIH 3T3 cells). More importantly, the cells transfected with the chitosan- graft -PEI-PEG/pCMV-EGFP-Ntf3 complex produced sustained neurotrophin-3 with a linear increase in cumulative concentration, which induced neuronal differentiation of neural stem cell and promoted neurite outgrowth . These findings suggested that our multifunctional copolymers might be ideal nanovectors for engineering cells via gene transfection, and could potentially be applied in tumor therapy and regenerative medicine. Statement of Significance We successfully prepared a multifunctional gene delivery nanovector containing branched PEI with a molecular weight of 2000 Da to balance between biocompatibility and transfection efficiency, and RGD/TAT peptides for enhanced targeting ability and cellular uptake. The well-formed CPPP/DNA complexes of small particle size and reasonable positive charges potentially enhanced gene transfection in both tumor and normal cells. More importantly, the CPPP/pCMV-EGFP-Ntf3 complex-transfected 293T cells could produce sustained NT-3 with a constant ratio, which induced neuron differentiation of NSC and promoted neurite outgrowth. Therefore, our study provided an effective strategy for producing neurotrophins by engineering cells with gene delivery, which deserved wide investigation and potential application in regenerative medicine.

研究领域: 生物材料学 · 神经科学 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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Heliyon · 2023 · IF 4

Temozolomide and chloroquine co-loaded mesoporous silica nanoparticles are effective against glioma

Peng Zhang,Fang Cao,Jiqin Zhang,Ying Tan,Shengtao Yao

The past decades have witnessed great progress in nanoparticle‐based cancer‐targeting drug delivery systems, but their therapeutic potentials is yet to be fully exploited. In this research, temozolomide (TMZ) and chloroquine (CQ) were loaded into the mesoporous silica nanoparticles (MSNs), the surface was coated with polydopamine (PDA), and the complex was coupled with arginine-glycine-aspartic (RGD) to successfully prepare TMZ/CQ@MSN-RGD. RGD-MSNs accumulated more in the cell and tumor models than in unmodified MSNs in the in vitro and in vivo experiments and can directly induce apoptosis and autophagy in tumor cells. In addition, TMZ/CQ@MSN-RGD therapy enhanced the apoptosis effect of the RGD-MSNs in glioma. Therefore, the combination of autophagy inhibitor with chemotherapy drugs in nanocarriers may promote therapeutic efficacy in treating glioma.

研究领域: 肿瘤学 · 纳米医学 · 药理学
✓ 已验证 DOI 高影响因子
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ACS Applied Materials & Interfaces · 2015 · IF 6.723

Development of Large-Scale Size-Controlled Adult Pancreatic Progenitor Cell Clusters by an Inkjet-Printing Technique

Jia Yang,Fang Zhou,Rubo Xing,Yuan Lin,Yanchun Han,Chunbo Teng,Qian Wang

The generation of transplantable β-cells from pancreatic progenitor cells (PPCs) could serve as an ideal cell-based therapy for diabetes. Because the transplant efficiency depends on the size of islet-like clusters, it becomes one of the key research topics to produce PPCs with controlled cluster sizes in a scalable manner. In this study, we used inkjet printing to pattern biogenic nanoparticles, i.e., mutant tobacco mosaic virus (TMV), with different spot sizes to support the formation of multicellular clusters by PPCs. We successfully achieved TMV particle patterns with variable features and sizes by adjusting the surface wettability and printing speed. The spot sizes of cell-adhesive TMV mutant arrays were in the range of 50–150 μm diameter. Mouse PPCs were seeded on the TMV-RGD (arginine–glycine–aspartate)-patterned polystyrene (PS) substrate, which consists of areas that either favor (TMV-RGD) or prohibit (bare PS) cell adhesion. The PPCs stably attached, proliferated on top of the TMV-RGD support, thus resulting in the formation of uniform and confluent PPC clusters. Furthermore, the aggregated PPCs also maintained their multipotency and were positive for E-cadherin, indicating that the formation of cell–cell junctions is critical for enhanced cell–cell contact.

CAS / MDL: 9003-53-6
研究领域: 生物医学工程 · 细胞生物学 · 糖尿病研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2015 ·Vol. 183 ·期 2 ·683-688 · IF 3.741

A cytosensor based on NiO nanoparticle-enhanced surface plasmon resonance for detection of the breast cancer cell line MCF-7

Jia Shengsong,Li Pengfei,Koh Kwangnak,Chen Hongxia

The article describes the use of a designed histidine (His)-tagged arginine-glycine-aspartic acid (RGD) peptide as a linker to bind integrin to captured cancer cells, and how to amplify the surface plasmon resonance (SPR) signal after binding of NiO nanoparticles (NiO-NPs) via the His-tag on the peptide. Specifically, breast cancer cells were captured via the interaction between human mucin (MUC-1) and a gold surface modified with a MUC-selective aptamer. The resulting cytosensor exhibits specificity and high sensitivity which is due to the enhancement of the SPR signal by NiO-NPs. The breast cancer cell line MCF-7 can be easily distinguished from normal islet beta cells by using this biosensor. Implementation of the His-tagged RGD peptide modified with NiO-NPs resulted in 20-fold enhancement of the SPR signal at the limit of detection. Hence, the actual limit of detection is lowered to 136 cells per mL. In our perception, this cytosensor has a large clinical potential in that it may also be used to detect various other kinds of tumor cells. Histidine-tagged arginine-glycine-aspartic acid peptide carried by NiO interacts with the integrin of cancer cells and amplifies the SPR signal resulting from interaction between human mucin (MUC-1) and a gold surface modified with a MUC-selective aptamer. As little as 136 cells·mL −1 are detectable.

CAS / MDL: 1313-99-1
研究领域: 生物传感技术 · 肿瘤检测 · 医学诊断
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JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY · 2023 ·Vol. 332 ·期 4 ·1237-1244 · IF 1.6

A novel superparamagnetic iron oxide nanoparticles-based SPECT/MRI dual-modality probe for tumor imaging

Xi Wenke,Zhang Ge,Xue Jingquan,Li Juan,Liu Yu,Wang Jianjun,Yang Wenjiang

Multimodal imaging has become a trend in the development of molecular imaging. For SPECT/MRI dual-modality imaging, we developed a SPECT/MRI dual-modality probe based on superparamagnetic iron oxide nanoparticles. RGDyk peptide and DTPA chelator were used to realize the functionalization of nanoparticles. Both SPECT imaging and T2-weighted MR imaging in vivo on 4T1 tumor-bearing mice showed targeting of the probe, demonstrating the potential of the SPECT/MRI dual-modality probe as a tool for tumor evaluation and diagnosis.

研究领域: 医学影像学 · 分子生物学 · 纳米医学
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Journal of Materials Chemistry B · 2021 ·Vol. 9 ·期 19 ·4024-4030 · IF 6.331

High-throughput hyaluronic acid hydrogel arrays for cell selective adhesion screening

Cong Wang,Hongye Hao,Jing Wang,Yunfan Xue,Junjie Huang,Kefeng Ren,Jian Ji

As a component of extracellular matrix (ECM), hyaluronic acid (HA) has plenty of applications in the biomedical field such as tissue engineering. Due to its non-adhesive nature, HA requires further grafting of functional molecules for cell related study. RGD and YIGSR are two kinds of cell adhesion peptides. YIGSR enhances endothelial cell (EC) adhesion, which is important for endothelialization after implantation of stents to prevent in-stent restenosis. However, the effect of combined densities of these peptides for EC and smooth muscle cell (SMC) adhesion has not been explored in a quantitative and high-throughput manner. In this work, single or orthogonal gradient densities of RGD and YIGSR were grafted onto the HA hydrogel array surfaces using thiol-norbornene click chemistry. Optimized peptide combinations for EC preponderant adhesion were found in hydrogel arrays and confirmed by scaling samples.

CAS / MDL: 2052-49-5
研究领域: 组织工程 · 生物材料 · 细胞生物学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MATERIALS & DESIGN · 2025 · IF 7.9

Biodegradable tetrasulfide bonds incorporated mesoporous polyamidoamine nanoplatform for enhancing antitumor efficiency via photothermal enhanced GSH depletion

Xiuhua Lin,Suhua Jiang,Siting Zhang,Huaqin Zhang,Xin Lin,Jiaping Lin,Zhizong Shen

Owing to the heat resistance of heat shock proteins that trigger cellular antioxidants like glutathione (GSH), it is challenging to simultaneously inhibit the spread and metastasis of tumor nodules and prevent tumor recurrence using conventional photothermal therapy (PTT). In this research, for incorporation of PTT and GSH depletion, we utilized mesoporous polydopamine nanospheres doped with GSH-responsive tetrasulfide bonds (referred to as gMPDA) for the synergistic suppression of lung cancer cells. By incorporating Arg-Gly-Asp (RGD) peptides onto the surface (forming gMPDA-RGD), the stability and tumor-targeting specificity of this biodegradable nanoplatforms were markedly improved. In vitro studies testified that these innovative nanotherapeutics displayed an impressive photothermal conversion efficiency (η = 52.33 %) and efficient consumption of intracellular GSH, leading to the collapse of the PDA based nanoframe. Notably, the disruption of redox balance post-808 nm laser irradiation led to effective PTT and reactive oxygen species (ROS) production. Importantly, gMPDA-RGD manifested a strong tumor-targeting ability in lung tumor-bearing Balb/C mice under fluorescent imaging. The synergistic treatments led to complete elimination of tumor cells when exposed to 808 nm laser irradiation. This study underscored the potential of gMPDA-RGD as a potent nanomedicine for the synergistic therapy of PTT and GSH depletion in clinical malignant tumor.

✓ 已验证 产品关联 DOI 高影响因子
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2023 · IF 5

Dual-drug loaded hybrid nanoparticle for combined tumor cocktail chemo-photothermal therapy and anti-inflammation

Huiyun Shi,Ying Chen,Qianqian Guo,Ling Tao,Xingjie Wu,Xiangchun Shen,Wen Liu

Tumor chemotherapy (CT) and photothermal therapy (PTT) have been frequently used in combination to achieve photothermally controlled drug release and synergistic treatment with enhanced pharmaceutic efficacy. However, both CT and PTT can cause serious inflammation response during and after treatment, which would potentially lead to tumor relapse and/or metastasis. To overcome this obstacle, we prepared anti-inflammation drug curcumin (CUR) and anti-tumor drug doxorubicin (DOX) loaded polydopamine (PDA) nanoparticle through polymer self-assembly and dopamine (DA) self-polymerization, and decorated RGD peptide at nanoparticle surface. After being guided to subcutaneous 4T1 tumor site through RGD and integrin α v β 3 interaction, this dual-drug loaded nanoplatform not only showed outstanding anti-tumor efficacy against 4T1 tumor due to the synergistic effect between PDA mediated PTT and DOX chemotherapy (CT), but also was able to reduce inflammatory response during the treatment. This multi-modal nanoplatform largely resolves the side effect of combined CT-PTT, and significantly broadened its potential application in clinical.

研究领域: 纳米技术 · 肿瘤学 · 药学 · 生物医学工程
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Acta Biomaterialia · 2015 · IF 6.025

Hepatocyte spheroid culture on fibrous scaffolds with grafted functional ligands as an in vitro model for predicting drug metabolism and hepatotoxicity

Shili Yan,Jiaojun Wei,Yaowen Liu,Hong Zhang,Jianmei Chen,Xiaohong Li

The identification of a biologic substrate for maintaining hepatocyte functions is essential to provide reliable and predictable models for in vitro drug screening. In the current study, a three-dimensional culture of hepatocytes was established on highly porous fibrous scaffolds with grafted galactose and RGD to afford extensive cell–cell and cell–scaffold interactions spatially. The pore size and ligand densities indicated significant effects on the formation of hepatocyte spheroids in balancing the cell retention, adhesion, and migration on fibrous scaffolds. Fibrous scaffolds with an average pore size of 60   μm and surface grafting densities of galactose at 5.9   nmol/cm 2 and RGD at 6.9   pmol/cm 2 provided optimal microenvironments for hepatocyte infiltration and multicellular spheroid formation. Significant promotions were also demonstrated in the syntheses of albumin and urea and the activities of phase I (CYP 3A11 and CYP 2C9) and phase II enzymes . The in vitro metabolism tests on testosterone and acetaminophen by hepatocytes on the optimal scaffolds indicated the predicated clearance rates of 50.7 and 22.6   ml/min/kg, respectively, which were comparable to the in vivo values of rats. The in vitro hepatotoxicity tests on amiodarone hydrochloride and acetaminophen predicted the half maximal effective concentrations (EC50) to reflect the in vivo toxic plasma concentrations in human. In addition, the enzyme activities , predicted clearance rates and hepatotoxicity values of hepatocytes on the optimal scaffolds experienced sensitive responsiveness to specific inducers or inhibitors of CYP 3A11 and phase II enzymes, exhibiting in vivo – in vitro correlations to a certain extent. These results demonstrate the feasibility of hepatocyte spheroid culture on fibrous scaffolds as an potential in vitro testing model to predict the in vivo drug metabolism, hepatotoxicity, and drug–drug interactions.

研究领域: 药理学 · 组织工程 · 毒理学
✓ 已验证 DOI PubMed 高影响因子
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