ADVANCED FUNCTIONAL MATERIALS
·
2020
·Vol. 31
·期 3
·2004550
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IF 16.836
Yaping He,Ting Xiong,Siyu He,Hongyu Sun,Chenxi Huang,Xiaohong Ren,Li Wu,Laurence H. Patterson,Jiwen Zhang
Lung cancer is a serious threat to human health with the highest morbidity and mortality; metastatic lung cancer accounts for a majority of cancer-related deaths. Hence, there is considerable interest in developing efficient lung-targeted drug delivery systems to improve overall survival and quality of life of lung cancer patients. Based on the lung-targeting characteristics of cubic crosslinked cyclodextrin metal–organic framework (CDF) nanoparticles, this study shows the synthesis of a nanoplatform using RGD-functionalized CDF to co-deliver low-molecular-weight heparin (LMWH) and doxorubicin (DOX) for treatment of lung cancer. Rational design of the DOX-loaded RGD-CDF-LMWH nanoplatform (RCLD) is carried out. RCLD nanoparticles are efficiently targeted to lung tumors following intravenous administration; RCLD accumulation in the lung is 5.8 times greater than that in the liver. Moreover, RCLD inhibits migration and invasion of cancer cells in vitro and significantly diminishes lung tumor nodule count and area of spread in human A549 and murine B16F10 lung cancer models in vivo. Furthermore, RCLD does not show serum enzyme or histopathologic indicators of tissue damage or adverse hematologic effects. Therefore, the multiple antitumor activities of this novel RCLD nanoplatform, alongside its safety profile for normal tissues, strongly support its use for targeted treatment of lung cancer.
研究领域:
药剂学
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肿瘤学
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纳米医学
✓ 已验证
DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Kai Yue,Chao Yang,Yu You,Xueying Wang,Xinxin Zhang
Background A good understanding of the adhesion behaviors of the nanocarriers in microvessels in chemo-hyperthermia synergistic therapy is conducive to nanocarrier design for targeted drug delivery.Methods In this study, we constructed an artificial blood vessel system using gelatins with a complete endothelial monolayer formed on the inner vessel wall. The numbers of adhered NPs under different conditions were measured, as well as the interaction forces between the arginine–glycine–aspartic acid (RGD) ligands and endothelial cells.Results The experimental results on the adhesion of ligand–coated nanoparticles (NPs) with different sizes and morphologies in the blood vessel verified that the gelatin-based artificial vessel possessed good cytocompatibility and mechanical properties, which are suitable for the investigation on NP adhesion characteristics in microvessels. When the temperature deviated from 37 °C, an increase or decrease in temperature resulted in a decrease in the number of adhered NPs, but the margination probability of NP adhesion increased at high temperatures due to the enhanced Brownian movement and flow disturbance. It is found that the effect of cooling was less than that of heating according to the observed changes in cell morphology and a decrease in cell activity under the static and perfusion culture conditions within the temperature range of 25 °C–43 °C. Furthermore, the measurement results of change in the RGD ligand-cell interaction with temperature showed good agreement with those in the number of adhered NPs.Conclusion The Findings suggest that designing ligands that can bind to the receptor and are least susceptible to temperature variation can be an effective means to enhance drug retention.
研究领域:
生物医学工程
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纳米医学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2018
·
IF 3.789
Weifeng Lin,Guanglong Ma,Zhefan Yuan,Haofeng Qian,Liangbo Xu,Elie Sidransky,Shengfu Chen
Much attention has been drawn to targeted nanodrug delivery systems due to their high therapeutic efficacy in cancer treatment. In this work, doxorubicin (DOX) was incorporated into a zwitterionic arginyl–glycyl–aspartic acid (RGD)-conjugated polypeptide by an emulsion solvent evaporation technique with high drug loading content (45%) and high drug loading efficiency (95%). This zwitterionic nanoformulation showed excellent colloidal stability at high dilution and in serum. The pH-induced disintegration and enzyme-induced degradation of the nanoformulation were confirmed by dynamic light scattering and gel permeation chromatography. Efficient internalization of DOX in the cells and high antitumor activity in vitro was observed. Compared with the free drug, this nanoformulation showed higher accumulation in tumor and lower systemic toxicity in vivo. The DOX-loaded zwitterionic RGD-conjugated polypeptide vesicles show potential application for targeted drug delivery in the clinic.
研究领域:
药学
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肿瘤学
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生物材料科学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2020
·
IF 4.848
Li Ke,Li Peng,Wang Yang,Han Shuang
Postoperative recurrence is a common and severe problem in the treatment of gastric cancer; consequently, a prolonged course of chemotherapy treatment is inevitable. Monitoring by imaging could provide an accurate evaluation of the therapeutic effects, which would be beneficial to guide a treatment strategy adjustment over time. However, current imaging technologies remain insufficient for the continuous postoperative monitoring of gastric cancer. In this case, molecular imaging offers an efficient strategy. Targetable contrast agents are an essential part of molecular imaging, which could greatly enhance the accuracy and quality of monitoring. Herein, we synthesized a Mn-based contrast agent for magnetic resonance imaging (MRI) of gastric cancer monitoring. Initially, small-sized Mn3O4 nanoparticles (NPs) were synthesized. Then, a functionalized polyethylene glycol (PEG) lipid was attached to the surface of the Mn3O4 NPs, to improve biocompatibility. The targetable MRI contrast agent (Mn3O4@PEG-RGD NPs) was further prepared by the conjugation of the arginine-glycine-aspartic acid (RGD) peptides. The completed Mn3O4@PEG-RGD NPs had the small size of 7.3 ± 2.7 nm and exhibited superior colloidal stability in different solution environments. In addition, Mn3O4@PEG-RGD NPs exhibited reliable biotolerance and low toxicity both in vitro and in vivo. Imaging experiments amply demonstrated that Mn3O4@PEG-RGD NPs could efficiently accumulate in gastric cancer tissues and cells via RGD mediation, and immediately significantly increased the MRI effects. Through this study, we can conclude that Mn3O4@PEG-RGD NPs have the potential to be a novel MRI contrast agent for the postoperative monitoring of gastric cancer.
研究领域:
生物医学工程
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癌症研究
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医学影像
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 30
·6338-6346
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IF 4.726
Hao Hu,Yuanyuan You,Lizhen He,Tianfeng Chen
Angiogenesis is essential for tumorous progression and metastasis. The RGD (Arg–Gly–Asp acid) peptide has been demonstrated to be a remarkable targeting reagent and can be distinguished by the integrin receptor overexpressed in various human tumor cells. Mesoporous silica nanoparticles (MSNs) are one of the most promising carriers applied for delivery of drugs or genes. It is well known that NAMI-A is an excellent drug for antimigration of tumor cells. Targeting the tumor vasculature with RGD-modified nanomaterials is expected to be a promising strategy for cancer therapy. Herein we have investigated the antiangiogenic activity of NAMI-A-loaded and RGD peptide surface decorated mesoporous silica nanoparticles in vitro and in vivo. The results revealed that NAMI-A@MSN-RGD remarkably enhanced the cellular uptake and antiangiogenic efficacy in contrast to bare NAMI-A in vitro. The nanosystem of NAMI-A@MSN-RGD also exhibited inspiring antiangiogenic action in vivo. Furthermore, the RGD-functionalized nanodrug inhibited angiogenesis by means of apoptosis by triggering ROS-mediated DNA damage in human umbilical vein endothelial cells (HUVECs). Our results suggested that the use of RGD-peptide modified MSNs as a vehicle of anticancer drugs is an efficient way to construct cancer-targeted nanosystems with antiangiogenic activity.
研究领域:
药学
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纳米医学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 11
·6013-6026
·
IF 2.936
Li Liang,Shuwen Peng,Zhenwei Yuan,Chen Wei,Yuanyuan He,Jinrong Zheng,Yueqing Gu,Haiyan Chen
Active targeting of tumor receptors is a significant approach for cancer diagnosis. Additionally, development of photothermal agents for photothermal therapy (PTT) has attracted great interest in the field of nanomedicine. In the present study, copper sulfide (CuS) nanoparticles capped with bovine serum albumin (BSA), named CuS@BSA, was synthesized by a convenient method. Then, the near-infrared (NIR) fluorescence probe MBA and the tumor-targeting ligand cyclic RGD were further conjugated on the surface of CuS@BSA, and the obtained nanocomposite was named CuS@BSA-MBA-cRGD. The morphology, optical properties, biotoxicity, tumor-targeting capability and in vitro and in vivo tumor inhibition effect were all characterized comprehensively. This nanocomplex demonstrated enhanced photothermal effects and positive tumor targeting. Thus, the nanocomposite CuS@BSA-MBA-cRGD can used as a promising tumor-targeting PTT agent for simultaneous cancer imaging and photothermal treatment.
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2023
·
IF 0
Xiaoqing Zhai,Shusen Tang,Fanhu Meng,Jihong Ma,Aimei Li,Xiangyu Zou,Baolong Zhou,Fujun Peng,Jingkun Bai
The treatment of breast cancer relies heavily on chemotherapy, but chemotherapy is limited by the disadvantages of poor targeting, susceptibility to extracellular matrix (ECM) interference and a short duration of action in tumor cells. To address these limitations, we developed an amphipathic peptide containing an RGD motif, Pep1, that encapsulated paclitaxel (PTX) and losartan potassium (LP) to form the drug-loaded peptide PL/Pep1. PL/Pep1 self-assembled into spherical nanoparticles (NPs) under normal physiological conditions and transformed into aggregates containing short nanofibers at acidic pH. The RGD peptide facilitated tumor targeting and the aggregates prolonged drug retention in the tumor, which allowed more drug to reach and accumulate in the tumor tissue to promote apoptosis and remodel the tumor microenvironment. The results of in vitro and in vivo experiments confirmed the superiority of PL/Pep1 in terms of targeting, prolonged retention and facilitated penetration for antitumor therapy. In conclusion, amphipathic peptides as coloaded drug carriers are a new platform and strategy for breast cancer chemotherapy.
研究领域:
药学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2018
·
IF 2.829
Boyi Niu,Yixian Zhou,Ting Wen,Guilan Quan,Vikramjeet Singh,Xin Pan,Chuanbin Wu
Packaging enough genetic materials is necessary for gene delivery, but functional modification of the carriers may affect their gene loading capacity. In this study, RGD peptide-modified mesoporous silica nanoparticles were synthesized to investigate the influences of functionalization on their DNA adsorption and desorption behaviors. Effects of the functionalization degree of the nanocarriers and the adsorption conditions including DNA concentration, pH, ionic strength and temperature were studied. The DNA adsorption of the nanocarriers were enhanced by reducing pH or adding moderate amounts of ionic salt. Compared with nonfunctional nanoparticles, nanoparticles with low degree of functionalization possessed decreased DNA adsorption capacity but increased adsorption stability. High degree of functionalization resulted in both poor adsorption capacity and stability. Systematic studies showed that the adsorption processes were spontaneous and endothermic, and could be well described by pseudo-second-order kinetic model , Langmuir and Freundlich models. In summary, the DNA loading capacity of mesoporous silica nanoparticles can be improved by proper functionalization and optimized adsorption conditions.
研究领域:
生物材料学
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分子生物学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Lingna Deng,Fang Zhang,Yanlin Wu,Jiahao Luo,Xuhong Mao,Lingli Long,Maling Gou,Liqun Yang,David Y. B. Deng
Studies have shown that the use of proangiogenic genes can improve the prognosis of ischemic stroke by promoting angiogenesis at the injury site. For example, within this study, hypoxia-inducible factor 1-α (HIF-1α) has exhibited an angiogenic effect. Our previous study reported a more stable HIF-1α mutant form (HIF-1α-AA), which was transfected into mesenchymal stem cells to provide neuroprotective effects against ischemic stroke. The safety of nonviral gene vectors has attracted researchers’ attention. This study encapsulated the HIF-1α-AA plasmid DNA into a newly synthesized effective nonviral gene vector, a hyperbranched cationic amylopectin derivative (DMAPA-Amyp) nanocarrier. In addition, a targeting strategy was applied to select the RGD peptides and bind to the designed nanocarrier as a molecule targeting endothelial cells. The targeting strategy is used to directly deliver the nanocarriers to the vascular endothelial cells of the brain peri-infarct site. This study emphasizes the targeting ability of nanocarrier and its therapeutic effect on cerebral ischemia. The results showed that RGD-DMAPA-Amyp had good biocompatibility and a high cell uptake rate, indicating that it is a safe nonviral gene vector that can be endocytosed by human cells. In rat models of ischemic stroke, compared with the nontargeted nanocarrier group, more RGD-DMAPA-Amyp nanoparticles aggregated in vascular endothelial cells of the peri-infarct region and significantly improved the recovery of neurological function. It is indicated that the RGD-modified nanomedicine promotes the recovery of nerve function more efficiently. Further study on the mechanism of RGD-DMAPA-Amyp/HIF-1α-AA in the treatment of cerebral ischemia displayed potential to significantly promote the formation of new blood vessels in vivo. Our findings suggest that the RGD-modified nonviral gene vector containing HIF-1α-AA appears to be a safe and promising therapeutic strategy for ischemic stroke gene therapy.
研究领域:
神经科学
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分子生物学
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基因治疗
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药学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Zhang Yuan,Bailong Tao,Ye He,Ju Liu,Chuanchuan Lin,Xinkun Shen,Yao Ding,Yonglin Yu,Caiyun Mu,Peng Liu,Kaiyong Cai
To inhibit bacterial infection in situ and improve osseointegration are essentially important for long-term survival of an orthopedic implant , in particular for infection-associating revision surgery. Herein, we fabricate a functional molybdenum disulfide (MoS 2 )/polydopamine (PDA)-arginine-glycine-aspartic acid (RGD) coating on titanium (Ti) implant to address above concerns simultaneously. The coating not only improved the osteogenesis of mesenchymal stem cells (MSCs), but also endowed Ti substrates with effective antibacterial ability when exposing to near-infrared (NIR) irradiation. It accelerated glutathione (GSH) oxidation via photothermal energy and induced intrinsic ROS-independent oxidative stress damage deriving from MoS 2 nanosheets . The results displayed that RGD-decorated MoS 2 nanosheets significantly increased the cellular osteogenic behaviors of MSCs via up-regulating osteogenesis-related genes (ALP, Runx2, Col I and OCN) in vitro. Moreover, the functionalized Ti substrates demonstrated great antibacterial efficiency of over 92.6% inhibition for S. aureus and E. coli under NIR-irradiation. Hyperthermia induced by photothermal effect accelerated the GSH consumption and ROS-independent oxidative stress destroyed the integrity of bacteria membranes , which synergistically led to protein leakage and ATP decrease. Furthermore, co-culture experiment showed that S. aureus contamination was efficiently cleaned from MoS 2 /PDA-RGD surface after NIR photothermal treatment, while MSCs adhered and proliferated on the MoS 2 /PDA-RGD surface. In an S. aureus infection model in vivo, MoS 2 /PDA-RGD modified Ti rods killed bacteria with an efficiency of 94.6% under NIR irradiation, without causing damage to normal tissue. More importantly, the MoS 2 /PDA-RGD modified Ti implants accelerated new bone formation in comparison with TNT implants in vivo .
研究领域:
生物材料
·
生物医学工程
·
骨科
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Huifang Nie,Rong Huang,Guangwei Jiang,Wenshuai Li,Lan Yang,Meng Zhang,Min Qian,Wei Guo,Tao Ye,Rongqin Huang
Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α v β 3 because of the multivalent interactions between larger active nanoparticles and integrin α v β 3 . In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.
研究领域:
肿瘤学
·
纳米医学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
ANNALS OF BIOMEDICAL ENGINEERING
·
2020
·Vol. 48
·期 5
·1511-1523
·
IF 3.324
Ding Yilei,Zhao An-sha,Liu Tianmei,Wang Ya-nan,Gao Yuan,Li Jing-an,Yang Ping
In this contribution, an injectable hydrogel was developed with chitosan, gelatin, β-glycerphosphate and Arg-Gly-Asp (RGD) peptide: this hydrogel is liquid in room temperature and rapidly gels at 37 °C; RGD peptide promises better growth microenvironment for various cells, especially endothelial cells (EC), smooth muscle cells (SMC) and mesenchymal stem cells (MSC). Both stromal cell-derived factor-1 (SDF-1) nanoparticle and vascular endothelial growth factor (VEGF) nanoparticles were loaded in the injectable hydrogel to simulate the natural nanoparticles in the extracellular matrix (ECM) to promote angiogenesis. In vitro EC/SMC and MSC/SMC co-culture experiment indicated that the nanocomposite hydrogel accelerated constructing embryonic form of blood vessels, and chick embryo chorioallantoic membrane model demonstrated its ability of improving cells migration and blood vessel regeneration. We injected this nanocomposite hydrogel into rat myocardial infarction (MI) model and the results indicated that the rats heart function recovered better compared control group. We hope this injectable nanocomposite hydrogel may possess wider application in tissue engineering.
研究领域:
生物材料学
·
再生医学
·
心血管研究
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）