ACS Biomaterials Science & Engineering
·
2025
·
IF 5.5
Chengjun Sun,Qi Zhou,Guanzhi Lai,Shaojun Shi,Ming Han,Wuzheng Xia,Xiangling Wei,Yang Du,Rongji Ye,Shuiguo Tang,Linwei Wu,Shanzhou Huang
Hepatic fibrosis is a progressive liver disease characterized by excessive accumulation of extracellular matrix (ECM) proteins, primarily collagen, in response to chronic liver injury. Despite the availability of treatment options, current therapies face significant challenges, including poor drug targeting and systemic toxicity. In this study, we developed a nanodrug delivery system, Rosiglitazone (RGZ)-loaded perfluoropropane (PFP)-based lipid nanoparticles (LNPs) functionalized with Arg-Gly-Asp (RGD) peptides (RGZ/PFP@LNP-RGD), for ultrasound-assisted targeted therapy of liver fibrosis. RGZ, a selective PPARγ agonist, was encapsulated in LNPs functionalized with RGD peptides, allowing for targeted delivery to activated hepatic stellate cells (aHSCs), the central cells involved in fibrosis progression. PFP, incorporated into the nanoparticle core, serves as an ultrasound-responsive agent, enabling controlled drug release upon ultrasound irradiation. In vitro, RGZ/PFP@LNP-RGD treatment led to a reduction in the expression of key fibrosis markers such as Col Iα1, α-SMA, and TGF-β1 at both the protein and mRNA levels. Ultrasound treatment further enhanced RGZ release from the nanocarriers, improving the inhibition of HSC activation. In vivo, RGZ/PFP@LNP-RGD combined with ultrasound treatment resulted in a marked reduction in liver fibrosis and improved liver function compared to free RGZ treatment. Histological and biochemical assessments confirmed reduced fibrosis marker expression and liver damage. These results suggest that RGZ/PFP@LNP-RGD, especially when combined with ultrasound, offers a promising noninvasive therapeutic strategy for liver fibrosis, with enhanced targeting, controlled drug release, and reduced systemic toxicity.
研究领域:
纳米医学
·
药学
·
肝病学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Research Express
·
2021
·Vol. 8
·期 4
·045012
·
IF 1.62
Fei Ge,Rui Qiao,Ping Song,Yugui Tao,Longbao Zhu,Weiwei Zhang,Wanzhen Li,Lin Gui
Tumors area common cause of morbidity and mortality. High treatment efficiency and low drug toxicity are key for effective tumor treatment. Here, the pH-sensitive material ZIF-90 was synthesized by the liquid-phase diffusion method for loading paclitaxel (PTX), and the targeting peptide (RGD) was prepared by the solid-phase synthesis method to modify it (RGD/PTX@ZIF-90). The skeleton of RGD/PTX@ZIF-90 collapses in the acidic tumor microenvironment, thereby releasing PTX and mediating the controlled release of the drug. ZIF-90 below 300 nm was obtained by adjusting the ratio of metal ions and organic ligands in the characterization experiment. In addition, in vitro drug release experiments showed that the drug release rate was greater at pH = 5.5 than at pH = 7.4. The lethal rate of RGD/PTX@ZIF-90 to human breast cancer cells (MCF-7) was 44.5%, which was higher than the lethal rate of PTX alone (37.3%) in the cytotoxicity experiment and apoptosis experiment. Uptake experiments revealed that RGD/PTX@ZIF-90 mainly existed in the cytoplasm of MCF-7, which suggests that the drug had successfully entered the cell to achieve the therapeutic effect. The loading of the nano-medicine carrier ZIF-90 and the modification of the targeting peptide RGD significantly improve the therapeutic effect of PTX and indicate that this system could be used to treat breast cancer.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
ACS Omega
·
2023
·
IF 4.1
Nan Zhao,Qirui Sun,Lening Zhang,Hao Jin,Mengsi Zhang,Shuwei Liu,Hua Xin
In clinical practice, the incidence and mortality of non-small cell lung cancer are increasing year by year, which is a serious threat to the health of patients. Once the optimal surgical window is missed, the toxic side effects of chemotherapy have to be confronted. With the rapid development of nanotechnology in recent years, medical science and health have been greatly impacted. Therefore, in this manuscript, we design and prepare chemotherapeutic drug vinorelbine (VRL)-loaded polydopamine (PDA) shell-coated Fe3O4 superparticles, and further graft the targeted ligand RGD onto their surface. Because of the introduction of the PDA shell, the toxicity of the prepared Fe3O4@PDA/VRL-RGD SPs is greatly reduced. At the same time, due to the existence of Fe3O4, the Fe3O4@PDA/VRL-RGD SPs also have MRI contrast capability. Under the dual-targeting effect of RGD peptide and external magnetic field, Fe3O4@PDA/VRL-RGD SPs can accumulate into tumors effectively. The accumulated superparticles in the tumor sites can not only effectively identify and mark the location and boundary of the tumor under MRI, guideing the application of near-infrared laser, but also release the loaded VRL under the stimulation of the acidic microenvironment of the tumor to play the role of chemotherapy. On further combination with photothermal therapy under laser irradiation, A549 tumors are completely eliminated without recurrence. Our proposed RGD/magnetic field dual-targeting strategy can effectively improve the bioavailability of nanomaterials and contribute to better imaging and therapeutic effects, which has a promising application prospect in the future.
研究领域:
纳米技术
·
癌症研究
·
生物医学工程
·
分子生物学
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2022
·
IF 5.738
Long Yu,Shao Fuqiang,Ji Hao,Song Xiangming,Lv Xiaoying,Xia Xiaotian,Liu Qingyao,Zhang Yongxue,Zeng Dexing,Lan Xiaoli,Gai Yongkang
Ovarian cancer has the highest mortality rate of gynecologic malignancy. 18F-FDG positron emission tomography (PET) adds an important superiority over traditional anatomic imaging modalities in oncological imaging but has drawbacks including false negative results at the early stage of ovarian cancer, and false positives when inflammatory comorbidities are present. Aminopeptidase N (APN, also known as CD13) and integrin αvβ3 are two important targets overexpressed on tumor neo-vessels and frequently on ovarian cancerous cells. In this study, we used subcutaneous and metastatic models of ovarian cancer and muscular inflammation models to identify 68Ga-NGR-RGD, a heterodimeric tracer consisting of NGR and RGD peptides targeting CD13 and integrin αvβ3, respectively, and compared it with 18F-FDG. We found that 68Ga-NGR-RGD showed greater contrast in SKOV3 and ES-2 tumors than 18F-FDG. Low accumulation of 68Ga-NGR-RGD but avid uptake of 18F-FDG were observed in inflammatory muscle. In abdominal metastasis models, PET imaging with 68Ga-NGR-RGD allowed for rapid and clear delineation of both peritoneal and liver metastases (3-6 mm), whereas, 18F-FDG could not distinguish the metastasis lesions due to the relatively low metabolic activity in tumors and the interference of intestinal physiological 18F-FDG uptake. Due to the high tumor-targeting efficacy, low inflammatory uptake, and higher tumor-to-background ratios compared to that of 18F-FDG, 68Ga-NGR-RGD presents a promising imaging agent for diagnosis, staging, and follow-up of ovarian tumors.
研究领域:
肿瘤学
·
医学影像学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Shengqi Zang,Can Xiao,Maodian He,Bo Chen,Bingyao Liu,Shuai Yi,Lei Wang,Junxia Li,Xiaolei Shi,Shoushan Bu,Lei Jin
Biomimetic surface modification of scaffolds with osteoinductive molecules is a promising strategy for improving the bioactivity of scaffold and stimulating stem cell signals in bone tissue engineering. Zirconia (ZrO 2 ) offers excellent mechanical properties and biocompatibility, but its bio-inert nature hinders its use in bone regeneration applications. Recombinant human bone morphogenetic protein 7 (rhBMP-7) and arginine-glycine-aspartate (RGD) peptide were investigated for their potential use as surface-modifying biomolecules on the ZrO 2 scaffold. Our results showed that human dental pulp stem cells (hDPSCs) were induced to osteogenic differentiation by rhBMP-7 and RGD in a dose-dependent manner. Significantly enhanced alkaline phosphatase activity and up-regulated expression of osteogenic genes in hDPSCs were associated with rhBMP-7 and RGD grafting onto the ZrO 2 scaffold. Western blot analysis revealed that rhBMP-7 and RGD grafting led to activation of the SMAD1/5, p38 MARK, and ERK signaling pathways during hDPSCs differentiation. After 4 and 8 weeks of transplantation, the hDPSCs-seeded ZrO 2 -RGD-BMP-7 scaffold facilitated osteogenic differentiation and enhanced in vivo bone formation in critical-sized calvarial bone defects. The results support the simultaneous use of rhBMP-7 and RGD as surface-modifying biomolecules and hDPSCs as a source of osteogenic stem cells in conjugation with ZrO 2 -based porous scaffold for bone tissue engineering.
研究领域:
组织工程
·
生物材料
·
干细胞生物学
·
骨再生
✓ 已验证
产品关联
DOI
高影响因子
LANGMUIR
·
2024
·
IF 3.7
Xiaokai Pan,Juan Nie,Jiacheng Lei,Peng Wang,Kaikai Zheng,Qiang Wei,Xiaojing Liu
Understanding how the spatial distribution of adhesive ligands regulates cell behavior is crucial for designing biomaterials. This study investigates how precisely controlled ligand spacing affects cell spreading and integrin subtype engagement. Using engineered polyacrylamide hydrogels with gold nanoparticle arrays, we explored the impact of RGD ligand spacings (30 and 150 nm) on human mesenchymal stromal cells. Cells exhibited distinct morphological behaviors: smaller spacings promoted larger spreading areas, while larger spacings resulted in elongated shapes with reduced spreading. Mechanistically, we found that the α5β1 integrin, not the αvβ3 integrin, played a central role in mediating these responses, alongside lamellipodia formation. Our findings provide critical insights into the spatial sensing of ligands, highlighting the influence of ligand spacing on cellular mechanotransduction and integrin-specific responses. This work advances the understanding of cell-material interactions and offers potential strategies for designing biomaterials to guide cell behavior in tissue engineering.
研究领域:
细胞生物学
·
生物材料科学
·
组织工程
·
生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2018
·Vol. 10
·期 2
·228-234
·
IF 4.927
Chao Chen,Xiaofeng Guo,Jinhong Du,Bonnie Choi,Houliang Tang,Anchao Feng,San H. Thang
Miktoarm star (MAS) polymers are polymers with a number of distinct arms connected to a central core. Owing to their exclusive structure, MAS polymers have been extensively studied in recent years. To exploit their biomedical applications the combination of nucleic acids, peptides and saccharides are desired. In this study, RAFT polymerization of three monomers with markedly different properties, N,N-dimethylaminoethyl methacrylate (DMAEMA, cationic), n-butyl methacrylate (BMA, hydrophobic) and oligo(ethylene glycol) methyl ether methacrylate (OEGMA, hydrophilic) was conducted using an RGD peptide based RAFT agent as a chain transfer agent (RGD-CTA). With a disulphide dimethacrylate (DSDMA) redox-cleavable cross-linker, the above linear polymers were combined via an “arm-first” technique to access MAS polymers containing peptide arms. These MAS polymers showed excellent biocompatibility, cell staining performance and rapid redox responsiveness. The novel MAS polymers have potential as a prospective platform for intracellular drug/gene delivery for cancer therapy.
研究领域:
高分子化学
·
材料科学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Xiaoxin Yang,Chuang Zhang,Anxia Li,Jie Wang,Xiulan Cai
In the field of modern nanomedicine, ZnO nanoparticles were considered as an emerging candidate for drug delivery because of their inherent biocompatibility and stability. However, the poor dispersibility in a physiological medium obstructed their clinic applications. In this paper, the red fluorescence ZnO nanoparticles were synthesized, using a facile chemical method of polyol in boiling trimethylene glycol (TREG) with zinc acetate. The as-synthesized ZnO nanoparticles were first time grafted with PG layer through ring-opening polymerization of glycidol (ZnO-PG). As calculated from the TGA data, the weight ratio of the grafted PG was about 68 wt%. Then, the ZnO-PG engineered to conjugate with arginine-glycine-aspartate (RGD) peptide by stepwise organic reactions. Finally, anticancer drugs Doxorubicin hydrochloride (DOX) was immobilized on ZnO-PG-RGD (approximately 21.8 ± 0.9 nm) to form ZnO-PG-RGD/DOX. The drug release percentage reaches 70.6% within 48 h under pH 5.2, which was more than 3-fold higher than that pH 7.4. The properties of ZnO nanoparticles and its derivatives were detected by power XRD, TEM, EDS, FTIR, TGA, DLS, Zeta potential and UV. The grafted PG layer not only largely enhanced the dispersibility, but also inhibited ZnO nanoparticles from the uptake by U87MG and Hela cells. In contrast, ZnO-PG-RGD was selectively taken up by U87MG, not Hela cells, demonstrating an obvious targeting property. When ZnO-PG-RGD/DOX was used, U87MG cells showed specificity damaged compared with Hela cells. Thus, functionalized ZnO nanoparticle was a promising nanomaterial in cancer theranostics.
研究领域:
纳米医学
·
药学
·
癌症研究
·
材料科学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Xiaoxin Yang,Li Zhao,Luyi Zheng,Meiyun Xu,Xiulan Cai
An efficient surface engineering strategy for MnO nanoparticles was developed to attain enhanced colloidal stability, selective uptake by and toxicity to specific cancer cells. Specifically, MnO nanoclusters prepared by polyol method were grafted with polyglycerol (MnO-PG), and then conjugated with arginine-glycine-aspartate peptide (MnO-PG-RGD) through stepwise organic reactions. The physicochemical properties of the surface engineered MnO nanoclusters were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, zeta potential, transmission electron microscopy and high-resolution transmission electron microscopy. The grafted PG layer not only largely enhanced the dispersibility and colloidal stability of MnO nanoclusters in physiological media, but also effectively inhibited non-specific cellular uptake of MnO-PG. MnO-PG-RGD was selectively taken up by human glioblastoma U87MG cells overexpressing α vβ3 integrins through receptor-mediated endocytosis. The internalized MnO-PG-RGD was mainly located in the lysosomes of U87MG cells. The acidity of lysosomes accelerated Mn 2+ ions releasing, which promoted intracellular oxidative stress and further led to cell damage and apoptosis. The results indicate that appropriate surface functionalization can enable MnO nanoparticles to act as a potential anticancer agent in addition to their MRI functionality.
研究领域:
纳米技术
·
生物医学工程
·
癌症研究
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 44
·25318-25325
·
IF 3.049
Hanrui Li,Ke Li,Qi Zeng,Yun Zeng,Dan Chen,Liaojun Pang,Xueli Chen,Yonghua Zhan
Molecular imaging is a powerful tool for non-invasive visualization of tumors that plays an important role in their diagnosis and treatment. The specificity of molecular imaging probes for cancer cells is important for accurate tumor visualization, with antibody and polypeptide nanoprobe conjugates having often been used as targeting agents for tumor detection. However, many traditional chemical conjugation methods employ complex conjugation reactions that result in poor efficiency and poor bioactivity. Herein, we describe the use of photo click methodology for the rapid synthesis of nanoprobes comprised of silica nanoparticles functionalized with RGD targeting units (SiO2@T1-RGDk NPs) (∼80 nm) for in vivo prostate cancer fluorescent imaging applications. These SiO2@T1-RGDk NPs exhibit a maximum absorption wavelength of 380 nm in their UV absorption spectra with a maximum fluorescence emission wavelength of 550 nm. Confocal immunofluorescent imaging reveal that SiO2@T1-RGDk NPs exhibit excellent targeting ability for visualizing cancer cells, with in vivo fluorescence imaging intensity in a subcutaneous tumor model of prostate cancer reaching a maxima after 4 h. Biosafety assessments showed that SiO2@T1-RGDk NPs demonstrate no obvious toxicity in mice, thus demonstrated that these novel NPs may prove to be promising fluorescent imaging agents for the accurate detection and treatment of tumors.
研究领域:
纳米技术
·
生物医学工程
·
癌症研究
·
分子成像
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PROTEIN JOURNAL
·
2021
·Vol. 40
·期 5
·709-720
·
IF 2.371
Jiang Xuan,Zhang Xin,Fu Chao,Zhao Ruili,Jin Tianming,Liu Mengyue,Pan Chenhao,Li Liu An,Ma Jifei,Yu Enyuan,YU Xiaoxue,Hu Ye
Malignant melanoma, an increasingly common form of skin cancer, poses a significant threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. In this work, a new anti-tumor peptide, temporin La (T-La), was selected from a cDNA library generated from bullfrog skin. Two new derivative antitumor peptides, T-La (S) and T-La (FS), were designed by bioinformatics analysis and coupled with the RGD small molecule peptide to create chimeric RGD peptides, (RGD-T-La [S] and RGD-T-La [FS]). Preliminary experiments showed that the new antitumor peptides had significant antitumor effects. After coupling to the chimeric RGD peptide, the targeted treatment of mouse melanoma was significantly improved. Our data demonstrate that the 4 peptides tested herein significantly inhibited the proliferation, migration, and invasion of B16F10 cells; with an increase in polypeptide concentration, the proportion of melanoma cells in the G0/G1 phase decreased or increased significantly, respectively, the reactive oxygen species (ROS) content increased significantly, the mitochondrial membrane potential decreased significantly, and the expression of pro-apoptotic Bax, Caspase-3, and Caspase-9 increased, and anti-apoptotic Bcl-2 decreased significantly. Tyr and MITF genes were significantly downregulated. In conclusion, the use of these new anti-tumor peptides, when combined with a chimeric RGD peptide, may increase ROS levels and decrease mitochondrial membrane potential by inhibiting the activity of mitochondria, thus releasing apoptosis-promoting factors in B16F10 cells. The present study describes a new potential strategy for the application of promising peptides in the treatment of various cancers.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Huimin Zhou,Haixing Xu,Xin Li,Yahui Lv,Tian Ma,Shiying Guo,Zhijun Huang,Xiaobing Wang,Peihu Xu
This work reports a multifunctional nanoplatform ( [email protected] 2 -HA-RGD) by conjugating targeting ligand hyaluronic acid (HA) and RGD with mesoporous silica-coated gold nanorods ( [email protected] 2 ) for dual-targeted chemo-photothermal therapy. Doxorubicin hydrochloride (DOX) was used as the model drug to investigate the drug loading, in vitro drug release profiles and cell evaluation. The nanoplatform has demonstrated a good photothermal effect and excellent drug loading capacity of about 20.16%. It also had pH-enzyme sensitive and NIR-triggered drug release properties. Cellular uptake experiment results indicated that [email protected] 2 -HA-RGD can be dual-targeted to ovarian cancer cells via CD44 and integrin receptor mediated endocytosis pathway. Cytotoxicity experiments demonstrated that combined therapy exhibited a better therapy effect compared to that of single chemotherapy or photothermal therapy. Our study demonstrates that [email protected] 2 -HA-RGD may be a new promising dual-targeted delivery system for chemo-photothermal therapy.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
药学
✓ 已验证
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）