Scientific Reports
·
2025
·Vol. 15
·期 1
·1-12
·
IF 3.9
Li Silong,Li Na,Yin Qiangqiang,Zhang Zhichen,Hu Haifeng,Hao Liguo
This project aims to construct cRGD functionalized mesoporous silica nanoparticles and cRGD modified mesoporous silica nanoparticles for the diagnosis and treatment of tumors, providing new ideas for targeted therapy of tumors. The mesoporous silica nanoparticles were doped with gadolinium in situ to provide excellent imaging; cRGD was coupled on the particle surface to confer particle targeting; and hyaluronic acid was loaded onto the particles by electrostatic adsorption, thereby improving the biocompatibility of the particles and prolonging their in vivo circulation time.Taking pancreatic cancer as a model, we studied its targeting ability to pancreatic cancer and its phagocytosis to cancer cells; Using methods such as cell growth experiments and flow cytometry, the anti-cancer effect and pro apoptotic effect of the system were studied. In vivo distribution, tumor targeting and therapeutic efficacy of nanoparticles evaluated in a mouse model of pancreatic cancer with loaded tumors.Evaluate the bioavailability and enrichment of nanoparticles in tumor tissue using MRI technology. Evaluate the therapeutic effect and safety through changes in tumor volume, histopathological examination, and prognosis. Characterization of the synthesis results proved that cRGD-HA-DOX-Gd 2 O 3 @MSN (cHDG@MSN) was successfully synthesized with a particle size of 230.83 ± 12.36 nm.In vitro drug release experiments of DOX were carried out at different pH values (5.5 and 7.4), where the release was only up to 22.65% at pH 7.4, whereas DOX release was increased up to 78.75% at pH = 5.5.The results confirm the pH responsiveness of this nanocarrier platform.The results of cytotoxicity studies showed that cHDG@MSN itself is not cytotoxic. Biosafety evaluation and hemolysis test results confirmed that the probe is highly biocompatible.Notably, Gd 3+ significantly enhanced the T 1 contrast of the system according to MR imaging results.The apoptosis rates of SW1990 cells treated with PBS, DOX and cHDG@MSN in flow cytometry were 13.97%, 18.38% and 29.02%, respectively, demonstrating the effectiveness of the nanoprobes at the cellular level. Animal experiments demonstrated the effectiveness of nanoprobes at the pathological level and imaging level.Cells and animals demonstrated that cHDG@MSN effectively inhibited the proliferation of pancreatic cancer cells. This research further verified the pH sensitivity of the constructed compound drug delivery system to achieve accurate diagnosis and treatment of pancreatic cancer tumor cells.
研究领域:
肿瘤学
·
纳米医学
·
影像医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMER BULLETIN
·
2022
·Vol. 79
·期 12
·10555-10571
·
IF 2.843
Yu Lili,Yao Lin,Yang Kuan,Fei Wenling,Chen Qingqing,Qin Lan,Liu Shaojing,Cao Min,Liu Qian,Qin Bei
Nano core–shell drug carriers with high stability, low toxicity, and targeted drug delivery are significance for the delivery of anti-tumor drugs. In this study, Albumin from bovine serum (BSA), serving as a capping agent, was conjugated to MSNs via a cleavable disulfide bond to generate a redox-responsive nanocarrier (MSNs@BSA). Subsequently, cRGD peptide, as a targeting ligand, was modified on the particle surface by a protein cross-linker to obtain nanoparticles with tumor cell-targeting properties (RGD-MSNs@BSA). The construction of RGD-MSNs@BSA was confirmed by DLS analysis, scanning electron microscope (SEM), transmission electron microscopy (TEM), electron dispersive spectroscopy (EDS), X-Ray Diffraction (XRD), and Fourier Transform Infrared Spectroscopy (FTIR), respectively. It was displayed that the model anticancer drug doxorubicin (DOX) was efficiently and stably encapsulated in RGD-MSNs@BSA in the absence of glutathione (GSH), and an outbreak of DOX was observed when the particles were exposed to a GSH-containing environment. It demonstrated that disulfide-linked BSA capping can increase the drug loading stability, while enduing it redox sensitivity. Flow cytometry and fluorescence microscope tests displayed that cellular uptake of RGD-MSNs@BSA was much higher than that of particles without cRGD and free DOX. These results indicated that RGD-MSNs@BSA can increase drug tumor-targeting and drug cellular uptake.
研究领域:
纳米医学
·
药理学
·
生物材料科学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 112
·92292-92302
·
IF 3.84
Meng Cai,Mengyuan Ye,Xingxing Shang,Honghao Sun,Mingxing Liu,Hongmei Sun,Zhuo Ma,Hongda Zhu
Polymeric micelles as nanocarrier-based drug delivery systems provide an innovative platform for selectively delivering active molecules and offer better antitumour activity. However, circulation stability in vivo, controllable drug intracellular release and high targeting efficiency are several practical challenges for micelles. Therefore, we developed cRGD-modified and shell crosslinked micelles (RSCMs) based on amphiphilic poly(styrene-co-maleic anhydride) (SMA). RSCMs exhibited a spherical shape and were homogeneous with an average diameter of 106.1 nm and a low polydispersity of 0.087. In comparison, after crosslinking the micelles possessed better stability against dilution and stronger redox-response towards dithiothreitol (DTT). The SMA micelles displayed high drug loading capacity for hydrophobic DOX with a drug loading of approximately 14.1–19.2% (w/w) and an encapsulation efficiency of 72.1–82.7% (w/w). The in vitro release studies of shell crosslinked micelles showed that DOX release was minimal (<25%, 24 h) under physiological conditions. However, in the presence of 10 mM DTT, accelerated release of DOX was achieved (60%, 24 h). MTT assays in B16F10 cells indicated that RSCMs displayed low cytotoxicity up to a concentration of 500 μg ml−1. Moreover, the IC50 value showed that cRGD-DOX-ss-M could be more effective than other groups. In vitro, cellular uptake was further studied with confocal laser scanning microscopy and flow cytometry, both the qualitative and quantitative results demonstrated that cRGD-DOX-ss-M possessed much better specificity to cancer cells and superior stimulated release property in cytoplasm. Notably, cRGD-DOX-ss-M could more efficiently be delivered to and release into the nuclei of αvβ3 integrin over expressing tumor cell line (B16F10) than counterparts of integrin-deficient tumor cells (Hela). Thus, these cRGD-modified redox-sensitive micelles have appeared as a technology platform with great potential for targeted anticancer drug delivery and release for integrin over expressing tumor cells.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Li Ding,Xinghua Yu,Shihao Cai,Azhar Mahmood,Wenjing Meng,Xiaotong Liu,Jiahan Liu,Jieyun Li,Xuejuan Zhang,Chuanbin Wu
The cRGD peptide surface coating strategy for photothermal therapy nanoplatforms shows great promise in developing safe and effective cancer therapies. However, the precise intracellular mechanisms of these platforms remain unclear due to the complexity of intracellular trafficking and nano-bio interactions. This study investigates the nano-bio interactions of Bi 2 Se 3 nanofoams, a representative photothermal therapy nanoplatform, coated with cRGD peptide in cancer cells, focusing on endocytosis, exocytosis, and cellular trafficking. Our findings reveal that the cRGD-coated Bi 2 Se 3 nanofoams are internalized through three distinct endocytosis pathways: Rab34-mediated macropinocytosis, caveolae-dependent, and clathrin-dependent endocytosis. These nanofoams then accumulate in lysosomes via autophagy. Furthermore, inhibiting exocytosis reduces the loss of these nanofoams from cancer cells, enhancing photothermal and chemotherapy effects. This exocytosis-inhibiting strategy demonstrates significant potential for cancer therapy, validated by successful in vitro and in vivo results.
研究领域:
纳米医学
·
细胞生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Jianyu Ma,Zhouzhou Liao,Jinbo Li,Xiao Li,Hongling Guo,Qiyu Zhong,Jianyun Huang,Xintao Shuai,Shuqin Chen
Currently, hormonal therapy for endometriosis faces challenges in achieving a balance between treatment and preserving the chance of pregnancy. Therefore, the development of non-hormonal therapy holds significant clinical importance. Angiogenesis is a hallmark of endometriosis, and anti-angiogenic therapies targeting the hypoxia-inducible factor-1α (HIF-1α) pathway are considered potential approaches for endometriosis. However, angiogenesis is also involved in numerous physiological processes, including pregnancy, and systemic anti-angiogenesis may lead to severe adverse effects. To address this, a cRGD-modified liposome nanodrug (cRGD-LP-ART) is synthesized, which enhances drug efficacy while reducing adverse reactions. Artesunate (ART), a non-hormonal drug used to treat malaria, has shown anti-angiogenic effects beyond its original indications in various benign and malignant diseases. With cRGD modification, cRGD-LP-ART can target ectopic lesions and inhibit local angiogenesis by suppressing the HIF-1α/vascular endothelial growth factor (VEGF) pathway. Furthermore, cRGD-LP-ART exhibits better therapeutic effects than free ART, without affecting ovarian function or causing atrophy of the eutopic endometrium, making it a promising new option for non-hormonal therapy of endometriosis. As a combination of liposomes and a clinically approved drug, cRGD-LP-ART holds great potential and clinical prospects for the treatment of endometriosis.
研究领域:
药理学
·
妇科学
·
纳米医学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 36
·20087-20094
·
IF 2.936
Tingting Zhu,Ji Xiong,Zhongbo Xue,Yu Su,Fengnan Sun,Ran Chai,Jialiang Xu,Yaqing Feng,Shuxian Meng
Fluorescent probes have been demonstrated to be promising candidates as biomarkers and biological carriers. Our study focuses on the development of a novel amphiphilic fluorescent probe with good photostability, high water solubility, excellent specificity and promising loading capability for tumor diagnosis and treatment. At first, BODIPY dye and O-carboxymethyl chitosan were prepared via a chemical reaction. Then, the prepared BODIPY dye and cRGD were bonded to O-carboxymethyl chitosan successively via an acylation reaction. Finally, we obtained the desired amphiphilic fluorescent probe: BODIPY–O-CMC–cRGD, which was based on the fluorescence resonance energy transfer (FRET) principle for selective visualization of tumors in vitro. Through a series of experiments, we found that this fluorescent probe possessed better fluorescence characteristics and tumor targeting properties. Simultaneously, by self-assembly, the amphiphilic probe encapsulated the other flexible structure of BODIPY2 and the rigid structure of porphyrin, which formed distinct nanoparticles with different particle sizes. Hence, we could observe different phagocytosis processes of the two nanoparticles in the tumor cells via the fluorescence of dyes by confocal laser scanning microscopy. Therefore, the results suggest that the fluorescent probe has advantages in tumor detection, and the constructed tumor-specific nanoparticles show high clinical potential to be utilized not only in visual and precise diagnosis but also in excellent drug delivery for tumor treatment. Henceforth, we will prepare new targeted and visualized pharmaceuticals by replacing BODIPY2 and porphyrin with antineoplastic drugs for future tumor treatment.
研究领域:
生物医学工程
·
药学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Mingxing Qiu,Jiong Wang,Jiaojiao Bai,Xiaoxu Li,Cuiqing Tian,Zhi Liu,Chaoran Zheng,Andrew R. Clark,Xinwei Cheng,Xiaoyan Liao,Song Wu,Robert J. Lee,Xiaoju Zhou
Hepatocellular carcinoma (HCC) is one of the most common cancers, with high mortality. Chemotherapy is one of the main treatment options for HCC. However, the high toxicity and poor specificity of chemotherapeutic drugs have limited their clinical application. In this study, dual-ligand liposomes modified with glycyrrhetinic acid (GA) and cyclic arginine–glycine–aspartic acid (cRGD) (GA/cRGD-LP) were designed to target the GA receptor and αvβ3 integrin, respectively. The aim was to develop a highly selective targeted drug delivery system and further enhance the antitumor efficiency of drugs by targeting both hepatic tumor cells and vasculature. A novel lipid conjugate (mGA-DOPE) by coupling dioleoylphosphatidyl ethanolamine (DOPE) with methyl glycyrrhetinic acid (mGA) was synthesized, and its structure was confirmed. The targeting efficiency of GA/cRGD-LP by in vitro cellular uptake and ex vivo imaging was assessed. GA- and cRGD-modified doxorubicin-loaded liposomes (GA/cRGD-LP-DOX) were prepared, and their cytotoxicity in HepG2 and antitumor activity were evaluated. The results showed that the average particle size of the GA/cRGD-LP-DOX was 114 ± 4.3 nm, and the zeta potential was −32.9 ± 2.0 mV. The transmission electron microscopy images showed that the shapes of our liposomes were spherical. cGA/cRGD-LP-DOX displayed an excellent cellular uptake in both HepG2 and human umbilical vein endothelial cells. In the in vivo study, pharmacokinetic parameters indicated that cGA/cRGD-LP can prolong the circulation time of DOX in the blood. GA/cRGD-LP-DOX showed greater inhibition of tumor growth for HepG2-bearing mice than either the single-ligand-modified liposomes or nontargeted liposomes. GA/cRGD-LP-DOX displayed higher liver tumor localization than that of single-ligand-modified liposomes or free DOX. GA/cRGD-LP is a promising drug delivery system for liver cancer targeting and therapy and is worthy of further study.
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
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Jingxin Mo,Xianjue Chen,Meiying Li,Wenxu Liu,Wei Zhao,Lee Yong Lim,Richard D. Tilley,J. Justin Gooding,Qinghua Li
Glioblastoma is hard to be eradicated partly because of the obstructive blood–brain barrier (BBB) and the dynamic autophagy activities of glioblastoma. Here, hydroxychloroquine (HDX)-loaded yolk–shell upconversion nanoparticle (UCNP)@Zn0.5Cd0.5S nanoparticle coating with the cyclic Arg-Gly-Asp (cRGD)-grafted glioblastoma cell membrane for near-infrared (NIR)-triggered treatment of glioblastoma is prepared for the first time. UCNPs@Zn0.5Cd0.5S (abbreviated as YSN, yolk–shell nanoparticle) under NIR radiation will generate reactive oxygen species for imposing cytotoxicity. HDX, the only available autophagy inhibitor in clinical studies, can enhance cytotoxicity by preventing damaged organelles from being recycled. The cRGD-decorated cell membrane allowed the HDX-loaded nanoparticles to efficiently bypass the BBB and specifically target glioblastoma cells. Exceptional treatment efficacy of the NIR-triggered chemotherapy and photodynamic therapy was achieved in U87 cells and in the mouse glioblastoma model as well. Our results provided proof-of-concept evidence that HDX@YSN@CCM@cRGD could overcome the delivery barriers and achieve targeted treatment of glioblastoma.
研究领域:
纳米医学
·
癌症研究
·
神经科学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2019
·
IF 3.131
Lu Tian,Lei Tao,Hongyan Li,Shili Zhao,Yunfang Zhang,Shen Yang,Jianfeng Xue,Xianfeng Zhang
The exploration of drug delivery systems based on mesoporous structure materials shows great promise in nanomedcine. Herein, a multifunctional nanoplatform based on cyclic arginine-glycine-aspartic acid (cRGD) peptide-conjugated hollow mesoporous carbon nanoparticles (cRGD-HMCN) was developed to realize near-infrared (NIR)/pH-responsive drug release and targeted chemo-photothermal therapy. The cRGD-HMCN exhibited a high doxorubicin (DOX) loading efficiency of 246 μg/mg cRGD-HMCN and pH/NIR-responsive controlled drug release behavior. Also, taking the advantage of the high photothermal conversion efficiency, the HMCN could serve as a photothermal agent to realize photothermal therapy. The in vitro experimental results confirmed that DOX-loaded cRGD-HMCN (cRGD-HMCN@DOX) can significantly improve the therapeutic efficacy toward PC3 cells upon NIR laser irradiation, which was significantly more potent than that for non-targeted HMCN@DOX. More importantly, in vivo data from in the prostatic carcinoma (PC3) xenograft mouse model show that the tumor growth is effectively inhibited by treatment with cRGD-HMCN@DOX plus NIR irradiation with fewer side effects. Importantly, the synergistic group showed superior tumor growth inhibition as compared to that of nontargeted group and any monotherapy. Thus, it is expected that the HMCN could be a potential nanosystem to realizesynergistic chemo-photothermal therapy for cancer treatment.
研究领域:
纳米医学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
ANTI-CANCER DRUGS
·
2021
·Vol. 33
·期 1
·19
·
IF 2.248
Liu Shengli,Liu Honglian,Sun Hao,Deng Shengming,Yue Ling,Weng Zhen,Yang Jianfeng,Zuo Bin,He Yang,Zhang Bin
Albendazole (ABZ), a clinical antiparasitic drug, has shown potential antitumor effects in various tumors. Herein, we prepared dimeric cRGD [(cRGD) 2 ] modified human serum albumin (HSA) nanosystem to co-delivery of albendazole (ABZ) and iodine-131 ( 131 I) for chemoradiotherapy of triple-negative breast cancer (TNBC). [email protected] NPs were synthesized by the self-assembly method. 131 I-(cRGD) 2 / [email protected] NPs were fabricated through covalently binding [email protected] NPs with (cRGD) 2 peptides, followed by chloramine T direct labeling with 131 I. In vitro therapeutic effects on TNBC (MDA-MB-231 and 4T1 cells) were determined using MTT assay, crystal violet assay, wound-healing assay and western blotting analysis. In vivo treatment was performed using 4T1-bearing mice, and the tumor-targeting efficacy was assessed by gamma imaging. The distribution of NPs was quantitatively analyzed by detecting the gamma counts in tumor and main organs. The nanoparticles possessed negative charge, moderate size and good polydispersity index. Dual responding to pH and redox, the in vitro release rate of ABZ was more than 80% in 72 h. In vitro, NPs inhibited the proliferation of TNBC cells in a concentration-dependent manner and decreased cell migration. Western blotting analysis showed that the NPs, as well as free ABZ, cell-dependently induced autophagy and apoptosis by restraining or promoting the expression of p-p38 and p-JNK MAPK. In vivo, gamma imaging exhibited an earlier and denser radioactivity accumulation in tumor of 131 I-(cRGD) 2 / [email protected] NPs compared to NPs free of (cRGD) 2 conjugating. Furthermore, 131 I-(cRGD) 2 / [email protected] NPs significantly suppressed tumor growth by restraining proliferation and promoting apoptosis in vivo. Our study suggested that the nanoparticles we developed enhanced tumor-targeting of ABZ and increased antitumor effects by combination of chemotherapy and radiotherapy.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Zhenqian Wu,Chen Yuan,Qin Xia,Yan Qu,Han Yang,Qianming Du,Bohui Xu
Chitosan-based nanoparticles inevitably adsorb numerous proteins in the bloodstream, forming a protein corona that significantly influences their functionality. This study employed a pre-coated protein corona using cyclic Arg-Gly-Asp peptide (cRGD)-modified bovine serum albumin (BcR) to confer tumor-targeting capabilities on siVEGF-loaded chitosan-based nanoparticles (CsR/siVEGF NPs) and actively manipulated the serum protein corona composition to enhance their anti-tumor angiogenesis. Consequently, BcR effectively binds to the nanoparticles' surface, generating nanocarriers of appropriate size and stability that enhance the inhibition of endothelial cell proliferation, migration, invasion, and tube formation, as well as suppress tumor proliferation and angiogenesis in tumor-bearing nude mice. Proteomic analysis indicated a significant enrichment of serotransferrin, albumin, and proteasome subunit alpha type-1 in the protein corona of BcR-precoated NPs formed in the serum of tumor-bearing nude mice. Additionally, there was a decrease in proteins associated with complement activation, immunoglobulins, blood coagulation, and acute-phase responses. This modification resulted in an enhanced impact on anti-tumor angiogenesis, along with a reduction in opsonization and inflammatory responses. Therefore, pre-coating of nanoparticles with a functionalized albumin corona to manipulate the composition of serum protein corona emerges as an innovative approach to improve the delivery effectiveness of chitosan-based carriers for siVEGF, targeting the inhibition of tumor angiogenesis.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 16
·6134
·
IF 4.6
Shengchao Wang,Guiqiang Qi,Zhichen Zhang,Qiangqiang Yin,Na Li,Zhongtao Li,Guangyue Shi,Haifeng Hu,Liguo Hao
Clinically, magnetic resonance imaging (MRI) often uses contrast agents (CAs) to improve image contrast, but single-signal MRI CAs are often susceptible to calcification, hemorrhage, and magnetic sensitivity. Herein, iron acetylacetone and gadolinium acetylacetone were used as raw materials to synthesize a T1–T2dual-mode imaging gadolinium-doped iron oxide (GdIO) nanocluster. Moreover, to endow the nanoclusters with targeting properties and achieve antitumor effects, the cyclic Arg-Gly-Asp (cRGD) peptide and docetaxel (DTX) were attached to the nanocluster surface, and the efficacy of the decorated nanoclusters against pancreatic cancer was evaluated. The final synthesized material cRGD-GdIO-DTX actively targeted αvβ3on the surface of Panc-1 pancreatic cancer cells. Compared with conventional passive targeting, the enrichment of cRGD-GdIO-DTX in tumor tissues improved, and the diagnostic accuracy was significantly enhanced. Moreover, the acidic tumor microenvironment triggered the release of DTX from cRGD-GdIO-DTX, thus achieving tumor treatment. The inhibition of the proliferation of SW1990 and Panc-1 pancreatic cancer cells by cRGD-GdIO-DTX was much stronger than that by the untargeted GdIO-DTX and free DTX in vitro. In addition, in a human pancreatic cancer xenograft model, cRGD-GdIO-DTX considerably slowed tumor development and demonstrated excellent magnetic resonance enhancement. Our results suggest that cRGD-GdIO-DTX has potential applications for the precise diagnosis and efficient treatment of pancreatic cancer.Keywords:T1–T2;DTX;MRI;drug delivery;pancreatic cancer
研究领域:
医学影像学
·
纳米技术
·
肿瘤学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）