ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Xiao-Meng Liu,Zhen-Zhen Zhu,Xin-Rui He,Yun-Hong Zou,Qian Chen,Xiao-Ya Wang,Hui-Mei Liu,Xin Qiao,Xu Wang,Jing-Yuan Xu
Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.
研究领域:
癌症研究
·
纳米技术
·
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Xin Jin,Jianping Zhou,Zhenhai Zhang,Huixia Lv
Synergistic combination therapy involving the integration of chemotherapeutics and chemosensitizers into micelles has demonstrated great potential for tumor-specific location release. Here, the natural product betulinic acid (BA) and chemical drug lonidamine (LN) were used as chemosensitizers in combination with doxorubicin (DOX) for ovarian cancer treatment. We designed pH-sensitive peptide derivatives and constructed an all-in-one multifunctional multidrug pH-sensitive targeting delivery system for the synergistic co-delivery of DOX and BA (or LN). The combination of DOX and BA was found to elicit better therapeutic effects and lower cardiotoxicity than the DOX and LN combination in Skvo3 cells. Further, loading DOX/BA into the present micellar systems enabled burst release at the tumor location, leading to enhanced anti-tumor effects and reduced off-target effects. More importantly, DOX/BA micelles elicited fewer adverse effects on cardiac function and leukocyte counts in Skvo3 subcutaneous xenograft models. These features suggest that the designed micelles represent a promising multifunctional strategy for the efficient treatment of ovarian cancer.
研究领域:
药学
·
癌症研究
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION
·
2018
·Vol. 33
·期 2
·512-523
·
IF 0.524
Zhou Huimin,Gao Yuxiang,Xu Haixing,Li Xin,Lü Yahui,Ma Tian,Cai Xinjie,Li Rui,Wang Xiaobing,Xu Peihu
A multifunctional drug delivery system (GNRs@mSiO 2 -HA-RGD) was developed by conjugating targeting ligand hyaluronic acid (HA) and RGD with mesoporous silica- coated gold nanorods (GNRs@mSiO 2 ) for dual-targeted chemo-photothermal therapy. The physiochemical properties of the prepared nanoparticles were characterized by FTIR, UV-vis spectra, and 1 H NMR. Doxorubicin hydrochloride (DOX), an anticancer drug, was used as the model drug to investigate the drug loading, in vitro drug release profiles and cytotoxicity. The experimental results show that DOX-GNRs@mSiO 2 -HA-RGD is synthesized with a mean diameter of 116 nm and a sufficient load capacity of about 19.8%. It also has pH-enzyme sensitive and NIRtriggered drug release manner. Cellular uptake indicates that DOX-GNRs@mSiO 2 -HA-RGD exhibits a higher cellular uptake via CD44 receptor and integrin receptor mediated endocytosis compared with the GNRs@ mSiO 2 modified with one receptor or no receptor. In comparison with chemotherapy or photothermal therapy alone, DOX-GNRs@mSiO 2 -HA-RGD displayes the synergistic effects and achieves a higher therapeutic efficacy. It can be expected that DOX-GNRs@mSiO 2 -HA-RGD is a potential dual-targeted chemo-photothermal therapeutic platform for effective cancer treatment.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
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药学
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生物医学工程
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产品关联
DOI
高影响因子
Biomaterials Science
·
2017
·Vol. 5
·期 12
·2501-2510
·
IF 4.21
Zhaopei Guo,Xingzhi Zhou,Mengze Xu,Huayu Tian,Xuesi Chen,Meiwan Chen
Camptothecin (CPT) is a broad spectrum anticancer drug, but its application is limited due to the poor water solubility, lactone ring instability, and low drug loading potential. In this study, biocompatible cationic polypeptide-based micelles were developed to deliver dimeric CPT (DCPT) with the aim of overcoming the above-mentioned obstacles and achieving favorable therapeutic effects. Cationic polypeptide poly-lysine-block-poly-leucine (PLys-b-PLeu) was fabricated via the ring-opening polymerization of N-ε-carbobenzoxy-L-lysine (ε-Lys(Z)) and L-leucine (Leu) and further grafted with polyethylene glycol (PEG) and an arginine-glycine-aspartic acid (RGD) peptide. DCPT was synthesized by reacting CPT and 2-hydroxyethyl disulfide, and micelles were prepared using a dialysis method. The obtained DCPT-loaded RGD-PEG-g-poly-L-lysine-b-poly-L-leucine (DRPPP) micelles showed a high encapsulation efficiency of 89.7% and a high drug loading capacity of 46.1%. In addition, the DRPPP micelles remained stable under physiological conditions (PBS at a pH of 7.4) but showed rapid release when triggered by a reductive environment (PBS at a pH of 7.4 with 10 mM dithiothreitol). Compared to micelles without RGD decoration, the DRPPP micelles exhibited an increased cellular uptake through RGD targeting and were internalized into cells via caveolae-mediated endocytosis and macropinocytosis. Furthermore, the DRPPP micelles exerted an enhanced cytotoxicity against MDA-MB-231 cells compared to MCF-7 cells, which expressed less αvβ3 receptors. Besides, the DRPPP micelles induced cell apoptosis and caused a decrease of mitochondrial membrane potential. These results indicate that dimeric camptothecin-loaded cationic polypeptide-based micelle is a promising strategy for cancer therapy.
研究领域:
药学
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纳米技术
·
癌症治疗
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Science of Advanced Materials
·
2020
·Vol. 12
·期 5
·725-732
·
IF 1.117
Yu Fangfang,Li Jiaping,Yang Yan,Cheng Yueyue,Ni Xianwei,Wei Kaineng,Liu Zhe
By using an organic framework to fabricate functional biomaterials, novel design and advanced biomedical applications of polymeric microbubbles for in vivo targeting and disease-oriented imaging of tumor vascularization can be developed. The present study describes novel synthetic
protocols to fabricate RGD (Arginine-Glycine-Aspartic)-tagged αvβ3-targeted ultrasound microbubbles. The microbubbles were synthesized by emulsion polymerization techniques. Two types of microbubbles (MBs-1 and MBs-2) were obtained via biotin-streptavidin conjugation
to poly(butyl cyanoacrylate) microbubbles (MBs-0) obtained by one-step synthesis in reverse order. The size distributions and surface zeta potentials were characterized. The results showed that the sizes of the MBs-2 were larger than that those of the MBs-1, and the MBs-2 showed decreased
charge compared to MBs-1. In cell targeting studies, MBs-2 exhibited relatively stronger targeting affinity for αvβ3 integrins, while MBs-1 showed weaker targeting capability. Furthermore, in vivo mice imaging using MBs-2 for intravenous injection exhibited
an obvious and sustained signal increase, which revealed the accumulative of MBs-2 anchoring in tumor. Hence, MBs-2 have been proven to be a promising candidate for using as ultrasound contrast agents for the early diagnosis of αvβ3-overexpressing malignant tumors,
including breast cancer.
研究领域:
生物医学工程
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药学
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癌症研究
·
超声成像
✓ 已验证
DOI
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 13
·2338-2350
·
IF 4.872
Yuanyuan Guo,Boning Niu,Qingle Song,Yongdan Zhao,Yuling Bao,Songwei Tan,Luqin Si,Zhiping Zhang
Developing multifunctional nanoparticles (NPs) to improve therapeutic efficacy is highly desirable in cancer therapy. In an attempt to respond to such a challenge, a novel copolymer, D-α-tocopherol polyethylene glycol succinate-SS-poly(lactide) (TPGS-SS-PLA) with a disulfide linkage between the TPGS and PLA units, was synthesized for paclitaxel (PTX) delivery. PTX-loaded NPs were fabricated using a nanoprecipitation method to form a particle size of ∼130 nm with good in vitro stability, which can be disassociated under intracellular reductive conditions to release PTX rapidly. The detached TPGS can further promote the drug retention and cytotoxicity through its P-glycoprotein inhibiting property. Integrin-specific targeting peptide, cyclic RGD (cRGD), was further conjugated to the surface of the NPs for targeting the drug delivery. The RGD-decorated NPs exhibited enhanced cellular uptake, PTX accumulation and cell cytotoxicity as compared to non-targeted NPs on murine melanoma B16F10 cells, PTX-sensitive human ovarian A2780 cells and PTX-resistant A2780/T cells. In vivo evaluation of the targeted NPs further showed an extended half-life, increased AUC (area under the concentration–time curve), and significant tumor growth inhibition in mouse sarcoma S180- and B16F10-tumor bearing mice, with reduced side effects as compared to Taxol® and non-targeted NPs. These results indicate that the RGD decorated redox-sensitive NPs could deliver chemotherapies specifically inside the cell via receptor-mediated endocytosis with enhanced efficacy, especially in integrin αvβ3/αvβ5-rich tumor cells. Such a targeted nanocarrier against receptor clustering prepared from a non-cytotoxic and biodegradable copolymer might have great potential in cancer treatment.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 64
·39348-39358
·
IF 3.119
Xin-Min Guo,Jia-Lin Chen,Bao-Hui Zeng,Ji-Chuang Lai,Cui-Yan Lin,Mei-Yan Lai
Nanobubbles (NBs) are considered to be a new generation of ultrasound-responsive nanocarriers that can effectively target tumors, accurately release multi-drugs at desired locations, as well as simultaneously perform diagnosis and treatment. In this study, we designed theranostic NBs (FTY720@SPION/PFP/RGD-NBs) composed of RGD-modified liposomes as the shell, and perflenapent (PFP), superparamagnetic iron oxide nanoparticles (SPION), and fingolimod (2-amino-2[2-(4-octylphenyl)ethyl]-1,3-propanediol, FTY720) encapsulated as the core. The prepared FTY720@SPION/PFP/RGD-NBs were black spheres with a diameter range of 160–220 nm, eligible for enhanced permeability and retention (EPR) effects. The calculated average drug loading efficiency (LE) and encapsulation efficiency (EE) of the FTY720@SPION/PFP/RGD-NBs were 9.18 ± 0.61% and 88.26 ± 2.31%, respectively. With the promotion of low-intensity focused ultrasound (LIFU), the amount and the rate of FTY720 released from the prepared NB complex were enhanced when compared to the samples without LIFU treatment. In vitro magnetic resonance imaging (MRI) trials showed that the prepared FTY720@SPION/PFP/RGD-NBs had a high relaxation rate and MRI T2-weighted imaging (T2WI) scanning sensitivity conditions. The cell viability studies demonstrated that both HepG2 and Huh7 cells co-cultured with FTY720@SPION/PFP/RGD-NB (100 μg mL−1) + LIFU treatment had the lowest survival rate compared with the other groups at 24 h and 48 h, showing that FTY720@SPION/PFP/RGD-NB had the strongest anti-tumor efficiency among the prepared NBs. The cytotoxicity study also demonstrated that the prepared NBs had low toxicity to normal fibroblast 3T3 cells. Cellular uptake studies further indicated that both LIFU treatment and RGD modification could effectively improve the tumor-targeted effects, thereby enhancing the antitumor efficacy. The qRT-PCR results indicated that LIFU-mediated FTY720@SPION/PFP/RGD-NB could significantly cause the activation of Caspase3, Caspase9 and p53 compared to the control group, inducing HepG2 apoptosis. These results together indicated that FTY720@SPION/PFP/RGD-NBs combined with LIFU may serve as a multifunctional drug delivery platform for hepatocellular carcinoma treatment and provide a new strategy for tumor visualization by MRI.
研究领域:
生物医学工程
·
药学
·
癌症研究
·
医学影像
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
·
2022
·
IF 6.814
Chunhong Mo,Zhao Wang,Jianying Yang,Yiqiang Ouyang,Qian Mo,Shuting Li,Ping He,Limin Chen,Xinchun Li
Herein, we present the facile design and construction of a nanodrug system integrating targeted drug delivery and synergistic chemo-photothermal antitumor activity . MoS 2 nanosheets were synthesized and modified by α ν β 3 integrin binding peptide (Arg-Gly-Asp, RGD) using lipoic acid functionalized polyethylene glycol (LA-PEG-COOH), forming a well dispersed and targeted delivery nanocarrier . Further, covalent coupling of antitumor drug , thiolated doxorubicin (DOX) via disulfide linkage resulted in a novel nanodrug, RGD/MoS 2 /DOX. The prepared nanocarrier showed favorable stability, biocompatibility and photothermal conversion efficiency. Fluorescence imaging revealed that Hela cells could endocytose far more nanodrug than H9c2 normal myocardial cells due to the targeted delivery characteristic. Particularly, GSH-induced disulfide bond cleavage facilitated the effective release of DOX from the nanodrug in the tumor microenvironment . The survival rate of Hela cells incubated with the nanodrug for 48 h was 22.2 ± 1.2%, which dramatically reduced to 8.9 ± 1.4% in combination with 808 nm NIR irradiation, demonstrating powerful photothermal induced tumor-killing efficacy. In contrast, the survival rates of H9c2 cells treated by the nanodrug and free DOX were 68.5 ± 2.6% and 6.7 ± 2.6%, respectively, an indication of the notably alleviated cardiotoxicity of the designed nanodrug. The cell apoptosis experiment further verified the synergistic chemo-photothermal effect, thus paving a way toward design of high-efficiency and low-toxicity antitumor nanodrug.
研究领域:
纳米技术
·
药学
·
癌症研究
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Naizhen Zhou,Xiaoe Ma,Wanjun Hu,Pengfei Ren,Youliang Zhao,Tianzhu Zhang
The extracellular matrix (ECM) affects cell behaviors, such as survival, proliferation, motility, invasion, and differentiation. The arginine-glycine-aspartic acid (RGD) sequence is present in several ECM proteins, such as fibronectin, collagen type I, fibrinogen, laminin, vitronectin, and osteopontin. It is very critical to develop ECM-like substrates with well-controlled features for the investigation of influence of RGD on the behavior of tumor cells. In this study, poly(ethylene glycol) (PEG)-crosslinked poly(methyl vinyl ether- alt -maleic acid) (P(MVE- alt -MA)) hydrogels (PEMM) with different RGD contents were synthesized, fully characterized, and established as in vitro culture platforms to investigate the effects of RGD content on cancer stem cell (CSC) enrichment. The morphology, proliferation, and viability of SK-OV-3 ovarian cancer cells cultured on hydrogels with different RGD contents, the expression of CSC markers and malignant signaling pathway-related genes, and drug resistance were systematically evaluated. The cell aggregates formed on the hydrogel surface with a lower RGD content acquired certain CSC-like properties, thus drug resistance was enhanced. In contrast, the drug sensitivity of cells on the higher RGD content surface increased because of less CSC-like properties. However, the presence of RGD in the stiff hydrogels (PEMM2) had less effect on the stemness expression than did its presence in the soft hydrogels (PEMM1). The results suggest that RGD content and matrix stiffness can lead to synergetic effects on the expression of cancer cell stemness and the epithelial-mesenchymal transition (EMT), interleukin-6 (IL-6), and Wnt pathways.
研究领域:
生物材料
·
癌症生物学
·
细胞生物学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science China-Chemistry
·
2020
·Vol. 63
·期 8
·1100-1111
·
IF 6.356
Rong Yan,Zhang Zhen,He Chaoliang,Chen Xuesi
Cell-material and cell-cell interactions represent two crucial aspects of the regulation of cell behavior. In the present study, poly (L-glutamic acid) (PLG) hydrogels were prepared by catalyst-free click crosslinking via a strain-promoted azide-alkyne cycloaddition (SPAAC) reaction between azido-grafted PLG (PLG-N 3 ) and azadibenzocyclooctyne-grafted PLG (PLG-ADIBO). The bioactive peptides c(RGDfK) and N-cadherin mimetic peptide (N-Cad) were both conjugated to the PLG hydrogel (denoted PLG+RGD/N-Cad) in order to regulate cell-material and cell-cell interactions. Gelation time and storage modulus of the hydrogels were tunable through variations in the concentration of polypeptide precursors. The hydrogels degraded gradually in the presence of proteinases. The viability of bone marrow mesenchymal stem cells (BMSCs) was maintained when cultured with extracts of the hydrogels or encapsulated within the hydrogels. Degradation was observed within 10 weeks following the subcutaneous injection of hydrogel solution in rats, displaying excellent histocompatibility in vivo . The introduction of RGD into the PLG hydrogel promoted the adhesion of BMSCs onto the hydrogels. Moreover, when encapsulated within the PLG+RGD/N-Cad hydrogel, BMSCs secreted cartilage-specific matrix, in addition to chondrogenic gene and protein expression being significantly enhanced in comparison with BMSCs encapsulated in hydrogels without N-Cad modification. These findings suggest that these biodegradable, bioactive polypeptide hydrogels have great potential for use in 3D cell culture and in cartilage tissue engineering.
研究领域:
生物材料
·
干细胞生物学
·
组织工程
✓ 已验证
DOI
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Nengpan Zhang,Chunlin Li,Dayong Zhou,Chen Ding,Yaqing Jin,Qingmei Tian,Xiangzhou Meng,Kefeng Pu,Yimin Zhu
Thrombosis, a critical event in blood vessels, not only is associated with myocardial infarction and stroke, but also accounts for considerable morbidity and mortality. Thrombolytic drugs are usually applied to the treatment of acute myocardial infarction, acute cerebral infarction and pulmonary embolism. However, thrombolytic drugs show limited efficacy in clinical practice because of the short half-life in plasma and systemic side effects. In this study, the cyclic RGD (cRGD) functionalized liposomes were prepared to encapsulate urokinase , a cheap and widely used thrombolytic drug in clinic and better thrombolysis efficacy was achieved. The flow cytometry analysis showed that the cRGD liposomes could bind to the activated platelets while not to the resting platelets. In vitro release study revealed that the release percentage reached plateau in about 5 h with 60% urokinase being released from liposomes. Results from the in vitro thrombolysis experiments demonstrated a good thrombolysis potential of the cRGD urokinase liposomes. The in vivo thrombolysis study demonstrated that the cRGD liposomes could significantly reduce the dose of urokinase by 75% while achieving the equivalent thrombolysis effect as the free urokinase in mouse mesenteric thrombosis model. In conclusion, the cRGD liposomes encapsulating urokinase hold great promise in clinic for better thrombolytic efficacy. Statement of Significance In this paper, the cRGD liposomes were prepared to encapsulate urokinase for targeted thrombolysis therapy. The cRGD liposomes could specifically bind to the activated platelets and could stably and continuously release its loaded urokinase. The mouse mesenteric thrombosis model was established to evaluate the thrombolysis effect of the cRGD urokinase liposomes. The results demonstrated that the cRGD liposomes could improve the thrombolytic efficacy by almost 4-fold over free urokinase. In conclusion, the cRGD liposomes encapsulating urokinase had great potential for the clinical treatment of thrombosis.
研究领域:
药理学
·
治疗学
·
药物递送系统
·
心血管疾病
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Yilun Luo,Xiaowen Zheng,Peiqi Yuan,Xingyao Ye,Lie Ma
Due to the critical roles of macrophage in immune response and tissue repair, harnessing macrophage phenotypes dynamically to match the tissue healing process on demand attracted many attentions. Although there have developed many advanced platforms with dynamic features for cell manipulation, few studies have designed a dynamic chemical pattern to sequentially polarize macrophage phenotypes and meet the immune requirements at various tissue repair stages. Here, we propose a novel strategy for spatiotemporal manipulation of macrophage phenotypes by a UV-induced dynamic Arg-Gly-Asp (RGD) pattern. By employing a photo-patterning technique and the specific interaction between cyclodextrin (CD) and azobenzene-RGD (Azo-RGD), we prepared a polyethylene glycol-dithiol/polyethylene glycol-norbornene (PEG-SH/PEG-Nor) hydrogel with dynamic RGD-patterned surface. After irradiation with 365-nm UV light, the homogeneous RGD surface was transformed to the RGD-patterned surface which induced morphological transformation of macrophages from round to elongated and subsequent phenotypic transition from pro-inflammation to anti-inflammation. The mechanism of phenotypic polarization induced by RGD pattern was proved to be related to Rho-associated protein kinase 2 (ROCK2). Sequential modulation of macrophage phenotypes by the dynamic RGD-patterned surface provides a remote and non-invasive strategy to manipulate immune reactions and achieve optimized healing outcomes.
研究领域:
生物材料
·
组织工程
·
免疫学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）