COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Zhanxia Zhang,Changsheng Dong,Guanzhen Yu,Wei Cheng,Yupei Liang,Yongfu Pan,Hegen Li,Hongbin Ji
Targeting modifications and smart responsiveness of nanomedicines can enable anticancer drugs to be selectively delivered to and controllably released in tumour cells or tissues, which can reduce the treatment’s toxicity and side effects. Good biocompatibility is crucial for the clinical application of any nanomedicine. In this study, a double-targeting molecule, an RGD peptide- and 4-(2-aminoethyl) morpholine-modified, doxorubicin (DOX)-loaded bovine serum albumin (BSA) nanomedicine, that can be controllably released by the high levels of autophagic lysosomes in tumour cells was developed. The size of the spherical BSA nanoparticles is approximately 60 nm. In vitro experiments indicated that the RGD peptide- and 4-(2-aminoethyl) morpholine-modified, DOX-loaded BSA nanomedicine has a better therapeutic effect than free DOX. In vivo experiments suggested that the BSA nanomedicine can successfully suppress the progression of PC9 xenograft tumours. This phenomenon may be attributable to the endocytosis of a relatively large amount of nanomedicine and the effective release of the loaded chemotherapeutic agent, as induced by high levels of autolysosomes. Collectively, the results of this study provide a smart approach for increasing therapeutic efficacy using a double-targeting molecule-modified BSA nanomedicine.
研究领域:
纳米医学
·
癌症治疗
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Lijing Hao,Tianjie Li,Lin Wang,Xuetao Shi,Yan Fan,Chang Du,Yingjun Wang
Fibronectin (Fn) is significant to the performance of biomaterials, and the chemistry of biomaterial surface play important roles in Fn adsorption and subsequent cell behavior. However, the “molecular scale” mechanism is still unclear. Herein, we combined experimental strategies with molecular simulations to solve this problem. We prepared self-assembled monolayers with varying chemistries, i.e., SAMs-CH 3 , SAMs-NH 2 , SAMs-COOH and SAMs-OH, and characterized Fn adsorption and cell behaviors on them. Next, Monte Carlo method and all-atom molecular dynamics simulations were employed to reveal the orientation/conformation of Fn on surfaces. We found that SAMs-CH 3 strongly adsorbed Fn via hydrophobic interactions, but show poor bioactivity as the low exposure of RGD/PHSRN motifs and the deformation of Fn. SAMs-NH 2 and SAMs-COOH could adsorb Fn efficiently via vdW interactions, electrostatic interactions, hydrogen bonds and salt bridges. Fn exhibited excellent bioactivity for cell adhesion, proliferation and osteogenic differentiation as high exposure of bioactive motifs on SAMs-NH 2 , or as the activation of other inferior cell-binding motifs on SAMs-COOH. SAMs-OH showed poor Fn adsorption as the water film. However, the adsorbed Fn displayed non-negligible bioactivity due to high exposure of PHSRN motif and large degree of protein flexibility. We believe that the revealed mechanism presents great potential to rationally design Fn-activating biomaterials.
研究领域:
生物材料
·
分子生物学
·
细胞生物学
·
表面化学
·
生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Xiaodi Gong,Jing Wang,Linlin Yang,Lijuan Li,Xiaoyan Gao,Xiao Sun,Jingfeng Bai,Jichang Liu,Xin Pu,Yudong Wang
Chemodynamic therapy (CDT) relies on the tumor microenvironment (e.g., high H 2 O 2 level) responsive Fenton-like reactions to produce hydroxyl radicals (·OH) against tumors. However, endogenous H 2 O 2 is insufficient for effective chemodynamic responses. An NAD(P)H: quinone oxidoreductase 1 (NQO1) high catalase (CAT) low therapeutic window for the use of NQO1 bioactive drug β-lapachone (β-Lap) is first identified in endometrial cancer (EC). Accompanied by NADH depletion, NQO1 catalyzes β-Lap to produce excess H 2 O 2 and initiate oxidative stress, which selectively suppress NQO1 high EC cell proliferation, induce DNA double-strand breaks, and promote apoptosis. Moreover, shRNA-mediated NQO1 knockdown or dicoumarol rescues NQO1 high EC cells from β-Lap-induced cytotoxicity. Arginine-glycine-aspartic acid (RGD)-functionalized iron-based metal-organic frameworks (MOF(Fe)) further promote the conversion of the accumulated H 2 O 2 into highly oxidative ·OH, which in turn, exacerbates the oxidative damage to RGD-positive target cells. Furthermore, mitophagy inhibition by Mdivi-1 blocks a powerful antioxidant defense approach, ultimately ensuring the anti-tumor efficacy of stepwise-amplified reactive oxygen species signals. The tumor growth inhibition rate (TGI) is about 85.92%. However, the TGI of MOF(Fe)-based synergistic antitumor therapy decreases to only 50.46% in NQO1-deficient KLE tumors. Tumor-specific chemotherapy and CDT-triggered therapeutic modality present unprecedented therapeutic benefits in treating NQO1 high EC.
研究领域:
肿瘤学
·
药学
·
生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Yuan Feng,Kecen Xiao,Jinlin Chen,Jingjing Lin,Yuanyuan He,Xueling He,Fuyi Cheng,Zhen Li,Jiehua Li,Feng Luo,Hong Tan,Qiang Fu
The healing of wounds in diabetic patients is a huge challenge issue in clinical medicine due to the disordered immune. Recruiting endogenous cells to play a role in the early stage and timely reducing inflammation to promote healing in the middle or late of injuring are both prerequisites for effective treatment. Here, inspired by natural extracellular matrix, three-dimensional porous polyurethane-hyaluronic acid hybrid hydrogel scaffolds (PUHA) were prepared to repair diabetic wound through activate cell immunity by moderate foreign body reaction, provide cell adhesion growth extracellular matrix of hyaluronic acid (HA) and exhibit anti-inflammatory effect of polyurethane (PU). The interaction between PU and HA alters the compact PU hydrogel into macroporous PUHA hydrogel scaffolds with super-swelling, elastic mechanical properties, and controllable degradation, which are suitable for endogenous cells infiltration, growth and immune activation. Additionally, incorporating with RGD, PUHA hydrogel scaffolds with bioactive physicochemical features can evidently reduce the inflammation and modulate the polarization of macrophage apparently both in vitro and in vivo , mainly through downregulation of cytokine-cytokine receptor interaction genes, leading to reprogramming immune-microenvironment and rapid diabetic wound healing. This method of gathering cells initially and intervening immune-microenvironment in time provides an expected way to design biomaterials for chronic wound healing.
研究领域:
生物材料
·
组织工程
·
伤口愈合
·
免疫学
·
糖尿病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Dan Chen,Bowen Li,Songhua Cai,Peng Wang,Shuwen Peng,Yuanzhi Sheng,Yuanyuan He,Yueqing Gu,Haiyan Chen
Dual targeting towards both extracellular and intracellular receptors specific to tumor is a significant approach for cancer diagnosis and therapy. In the present study, a novel nano-platform (AuNC-cRGD-Apt) with dual targeting function was initially established by conjugating gold nanocluster (AuNC) with cyclic RGD (cRGD) that is specific to α v β 3 integrins over-expressed on the surface of tumor tissues and aptamer AS1411 (Apt) that is of high affinity to nucleolin over-expressed in the cytoplasm and nucleus of tumor cells. Then, AuNC-cRGD-Apt was further functionalized with near infrared (NIR) fluorescence dye (MPA), giving a NIR fluorescent dual-targeting probe AuNC-MPA-cRGD-Apt. AuNC-MPA-cRGD-Apt displays low cytotoxicity and favorable tumor-targeting capability at both in vitro and in vivo level, suggesting its clinical potential for tumor imaging. Additionally, Doxorubicin (DOX), a widely used clinical chemotherapeutic drug that kill cancer cells by intercalating DNA in cellular nucleus, was immobilized onto AuNC-cRGD-Apt forming a pro-drug, AuNC-DOX-cRGD-Apt. The enhanced tumor affinity, deep tumor penetration and improved anti-tumor activity of this pro-drug were demonstrated in different tumor cell lines, tumor spheroid and tumor-bearing mouse models. Results in this study suggest not only the prospect of non-toxic AuNC modified with two targeting ligands for tumor targeted imaging, but also confirm the promising future of dual targeting AuNC as a core for the design of prodrug in the field of cancer therapy.
研究领域:
纳米技术
·
癌症生物学
·
药物科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 19
·6528-6541
·
IF 6.843
Jiefei Peng,Ranran Wang,Wanru Sun,Minhua Huang,Rong Wang,Youjie Li,Pingyu Wang,Guangbin Sun,Shuyang Xie
Lung cancer is the second most common tumor and has the highest mortality rate. Both novel therapeutic targets and approaches are needed to improve the overall survival of patients with lung cancer. MicroRNA-320a-3p belongs to the miR-320a family and has been reported as a tumor suppressor in multiple cancers. However, its definitive role and precise mechanism in the progression of lung cancer remain unclear. In this study, we developed a new type of gold nanorod modified with polyethyleneimine that targets cancer-specific nanoparticles by RGD peptide, which could condense miRNA to self-assemble supramolecular nanoparticles. The designed nanoparticles can achieve integrin αvβ3-targeted cancer therapy, realize photosensitive therapy by laser irradiation and attain gene-targeted therapy by miRNAs. These nanoparticles could deliver miR-320a into lung cancer cells specifically and efficiently. Moreover, we demonstrated that Au-RGD-miR-320a nanoparticles combined with laser irradiation dramatically inhibited the proliferation and metastasis, and enhanced the apoptosis of lung cancer, both in vitro and in vivo. In terms of the mechanism, miR-320a inhibits Sp1 expression by directly binding to the 3′UTR of Sp1, and it eventually enhanced the expression of PTEN and inhibited the expression of matrix metallopeptidase 9 (MMP9). These findings provide a new and promising anticancer strategy via the use of Au-RGD-miR-320a nanoparticles, and identify miR-320a/Sp1 as a potential target for future systemic therapy against lung cancer.
研究领域:
肿瘤学
·
纳米技术
·
分子生物学
·
治疗学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Lulu Du,Wu Yiping,Qipeng Liu,Ying Xu,Wenyi Dai,Xingyi Li,Lei Lei,Zhishu Bao
In this work, we reported the generation of a bioactive peptide based supramolecular hydrogel as platform for efficient cell and drug delivery for ophthalmic application. The supramolecular hydrogelator was composed of a self-assemble motif ( e.g., NapFF) and a biofunctional moiety ( e.g., RGD) using glycine (G) as linker. Self-assembly behavior of amphiphile could be finely tuned by the number of glycine, and the optimized NapFFGGRGD amphiphile could self-assemble into supramolecular hydrogel in aqueous solution after heating–cooling procedure. The formed hydrogel was thoroughly characterized by transmission electron microscope (TEM), scanning electron microscope (SEM) and rheometer. The proposed NapFFGGRGD hydrogel exhibits great in vitro stability as incubation in cell culture medium for 7 days and supports human corneal epithelial cells (HCECs) proliferation in both 2D and 3D culture model. Both hydrophobic and hydrophilic drugs ( i.e., curcumin, vancomycin hydrochloride) could be readily encapsulated into NapFFGGRGD hydrogel without compromising their pharmacological activities. Using a rat model of bacterial keratitis (BK), we evidently demonstrated that vancomycin loaded NapFFGGRGD hydrogel (Van/NapFFGGRGD) effectively cure BK by the elimination of invaded bacteria and the promotion of corneal re-epithelization. As a result, the developed NapFFGGRGD supramolecular hydrogel might be a promising platform for efficient ophthalmic cell/drug delivery.
研究领域:
生物医学工程
·
药剂学
·
眼科
·
材料科学
·
生物化学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2013
·Vol. 1
·期 41
·5723-5732
·
IF 0
Guo-Feng Luo,Wei-Hai Chen,Yun Liu,Jing Zhang,Si-Xue Cheng,Ren-Xi Zhuo,Xian-Zheng Zhang
To develop a smart nanovalve on mesoporous silica nanoparticles (MSNs) for biomedical applications, a new type of peptide-functionalized MSN with a plug-gate nanovalve (PGN) was designed for targeted drug release in cancer cells. The outer shell of MSN was functionalized with K8 peptide (octa-lysine sequence) by click chemistry, followed by reacting with citraconic anhydride via α,β-unsaturated bond to prepare negatively charged MSN–K8(Cit). Subsequently, a cationic K8(RGD)2 peptide containing two Arg–Gly–Asp (RGD) sequences for targeting was introduced via electrostatic interaction to the negatively charged surface of MSN–K8(Cit) to form PGN. It was found that, at pH 5.0 (simulating the endo/lysosomal environment), the surface charge of MSN–K8(Cit) could convert from −41 mV to +19 mV due to the hydrolysis of the acid-labile amides in the acidic condition, implying the subsequent electrostatic repulsion to induce opening of the nanovalves and release of anticancer drug, DOX. According to the drug release studies, 79% of DOX was released within 48 h at pH 5.0, while much less DOX was released at pH 6.5 and 7.4. Furthermore, in vitro cellular experiments confirmed that the drug delivery system had enhanced cellular association and cell inhibition effect on αvβ3-positive U87 MG cancerous cells.
研究领域:
纳米技术
·
生物医学工程
·
药物递送系统
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
CHINESE JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 40
·期 5
·491-503
·
IF 3.815
Wu He-Cheng,Feng Yuan,Song Xing-Ying,Song Chun-Yang,Chen Jin-Lin,Wang Yan-Chao,He Xue-Ling,Liang Rui-Chao,Li Jie-Hua,Tan Hong
Improvement of the treatment for Glioblastoma multiforme (GBM) especially the development of in situ controllable drug release is still a major concern. In this study, we developed waterborne biodegradable polyurethane (WBPU) scaffolds incorporated with redox-sensitive and RGD-decorated paclitaxel (PTX) polymer-drug conjugates (PDCs) for targeted GBM therapy in situ . The drug scaffolds could be implanted at residual GBM site post-operation. Dual-targeting PTX-PDCs were obtained through step-by-step conjugation of disulfide linked PTX, poly(ethylene glycol) (PEG), and arginine-glycine-aspartic acid (RGD). The RGD-modified PTX-PDCs were spherical nanoparticles (NPs) that would be released from scaffolds and identified GBM cells actively. Internalized redox-sensitive PTX-PDCs would be decomposed and release PTX inside GBM cells under the circumstances of glutathione (GSH). The release profiles of PTX from the scaffolds with/without GSH were investigated. In vitro cytotoxicity assay revealed that the dual-targeting PTX-PDCs from scaffolds could specifically kill GBM cells and protect normal cells, suggesting that dual-targeting PTX-PDC-loaded scaffolds may have the potential to repair tumor-induced brain injury. In vivo anti-recurrence assay indicated that the PTX-PDC-scaffolds could deliver PTX-PDCs to the GBM cells followed by inhibiting tumor growth and inducing apoptosis. In general, the PTX prodrug-loaded devices exhibited significant anti-GBM effects and normal tissue protection simultaneously, indicating that the WBPU scaffolds incorporated with dual-targeting PTX-PDCs may be a promising strategy for local therapy of GBM.
研究领域:
生物医学工程
·
药学
·
神经科学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Yun Zeng,Yonghua Zhan,Xinyue Liu,Jingwen Ma,Huifang Liu,Hanrui Li,Tong Yi,Qingxia Zhu,Getao Du,Linfei Zhao,Dan Chen,Xueli Chen
Tumor metastasis is a major cause of poor cancer prognosis. Photothermal therapy (PTT) is a non-invasive, non-oxygen-dependent, and highly spatiotemporally precise treatment that may aid chemotherapy in suppressing tumor growth and metastasis. This article aims to develop and modify a CuS-based nanoplatform linking RGD-Acrk to actively target and internalize doxorubicin (DOX) into tumor cells, resulting in an alternating strategy of synergistic chemo/PTT. The nanoparticle’s shape, spectra, drug encapsulation efficiency, loading content, and controlled release are characterized, and a comparison of 808/980 nm lasers is used to irradiate the nanoplatform. The cell survival rate is used to determine the cytotoxicity of DOX and PTT, and the chemo/PTT is used to treat 4T1-Luc tumor-bearing mice. Simultaneously, bioluminescence and photoacoustic imaging are employed to assess therapy efficacy, as well as tumor size, weight, density, the bodyweight of mice, and survival curves. H&E, immunohistochemistry for HIF-1α, and TUNEL fluorescence staining confirm these findings, suggesting that the nanoplatform has a good active-targeted capacity and perform high-efficiency PTT caused by 980 nm laser irradiation. The synergistic effect is at least 3.53 times higher than chemo/PTT without synergistic effect and tumor liver metastasis is successfully suppressed, showing that it has the potential to be used for cancer treatment and prognosis improvement.
研究领域:
肿瘤学
·
纳米技术
·
诊疗学
✓ 已验证
DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Xinying Liu,Baohui Liu,Conglong Chen,Chaowei Hong,Jia Xu,Yixuan Ruan,Ling Huang,Shanni Hong,Wei Chen,Ye Kuang
A significant challenge in modern radiotherapy (RT) is to minimize the detrimental effects on adjacent healthy tissues while concurrently increasing the susceptibility of tumor tissue to radiation. Investigating nanoradiosensitizers with multifunctional properties has a lot of potential as a highly effective strategy for augmenting the efficacy of RT. A novel Janus Ag/Fe-HfO 2 nanoparticle was synthesized in a single-step process. This versatile nanoradiosensitizer combines photothermal capabilities, enzyme-like activities, and the capacity for magnetic resonance imaging (MRI). The surfaces have been meticulously engineered with PEG to boost biocompatibility and adorned with RGD-targeting peptides that selectively target tumor cells (Ag/Fe-HfO 2 -PEG-RGD). The characterization results have demonstrated the successful preparation of Janus Ag/Fe-HfO 2 nanoparticles with a diameter of roughly 10 nm. Furthermore, the photothermal properties, MRI ability, and enzymatic catalytic activities (generate O 2 , produce hydroxyl radical, and consume GSH) of Ag/Fe-HfO 2 -PEG-RGD were verified in vitro experiments. In vivo experiments, by integrating T 1 -weighted MRI-guided RT with the enzymatic activities of these nanoparticles, along with the application of photothermal heating, we have achieved a synergistic enhancement in the therapeutic efficacy of RT. Moreover, it stimulates tumor-specific immune responses, leading to an increased presence of tumor-infiltrating CD8 + T cells. This integrated multimodal nanotherapeutic platform, which capitalizes on the potent enhancement of RT effects, offers a promising new strategy in the ongoing battle against cancer.
研究领域:
纳米医学
·
肿瘤学
·
放射治疗
·
磁共振成像
·
生物无机化学
·
诊疗一体化
·
免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Jin Cui,Gongzheng Wang,Li Xian Yip,Mengzhen Dong,Mengyao Mu,Liya Tian,Yuan Gao,Qing Fan,Qiang Zhu,Xinya Zhao,Xueli Xu,David Tai Leong,Xiao Sun
Early detection and timely intervention are essential to prevent liver fibrosis from progressing to cirrhosis or hepatocellular carcinoma. Herein, utilizing the enhanced ferritin-manganese interaction by nanoplatinum growth, a novel ferritin-platinum-manganese magnetic resonance nanoplatform with RGD grafting and metformin loading (FNMMR) is developed. RGD can enhance the targeting ability of the nanoplatform toward integrin αVβ3 on activated hepatic stellate cells (aHSCs) in liver fibrosis. Systemic delivery of FNMMR shows clear degree-dependent magnetic resonance contrast enhancement in liver fibrosis. 3D reconstruction techniques and histogram-based features are achieved to qualitatively and quantitatively analyze the inhomogeneous liver fibrosis areas. FNMMR with catalase-like activity can catalyze the generation of O 2 to alleviate the liver fibrosis hypoxia and inhibit the expression of HIF-1α, blocking the TGF-β1/Smad signaling pathway. In addition, metformin shows synergy with HIF-1α reduction in blocking the TGF-β1/Smad pathway, effectively inhibiting the activation of HSCs and reducing collagen formation. Furthermore, FNMMR can achieve real-time anti-fibrotic therapy monitoring by magnetic resonance imaging. Importantly, no obvious side effects can be observed in both histological and hematology examinations. Therefore, this work presents a novel nanoplatform for accurate liver fibrosis diagnosis and synergistic anti-fibrotic therapy with real-time monitoring.
研究领域:
医学影像
·
纳米技术
·
药理学
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）