International Journal of Nanomedicine
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2023
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IF 8
Dinghu Zhang,Yanhong Chu,Hanqing Qian,Lingyu Qian,Jie Shao,Qiuping Xu,Lixia Yu,Rutian Li,Quanan Zhang,Fenglei Wu,Baorui Liu,Qin Liu
Introduction Gambogic acid (GA) is proved to have anti-tumor effects on gastric cancer. Due to poor solubility, non-specific biological distribution, toxicity to normal tissues and short half-life, it is hard to be applied into the clinic. To overcome these issues, we developed a thermosensitive and injectable hydrogel composed of hydroxypropyl cellulose, silk fibroin and glycerol, with short gelling time, good compatibility and sustained release, and demonstrated that the hydrogel packaged with gambogic acid nanoparticles (GA-NPs) and tumor-penetrating peptide iRGD could improve the anti-tumor activity.Methods The Gelling time and micropore size of the hydrogels were regulated through different concentrations of glycerol. Controlled release characteristics of the hydrogels were evaluated with a real-time near-infrared fluorescence imaging system. Location of nanoparticles from different carriers was traced by confocal laser scanning microscopy. The in vivo antitumor activity of the hydrogels packaging GA-NPs and iRGD was evaluated by investigating tumor volume and tumor size.Results The thermo-sensitive properties of hydrogels were characterized by 3–4 min, 37°C, when glycerol concentration was 20%. The hydrogels physically packaged with GA-NPs and iRGD showed higher fluorescence intensity than other groups. The in vivo study indicated that the co-administration of GA-NPs and iRGD by hydrogels had higher antitumor activity than the GA-loaded hydrogels and free GA combining with iRGD. Free GA group showed few antitumor effects. Compared with the control group, the body weight in other groups had no obvious change, and the count of leukocytes and hemoglobin was slightly decreased.Discussion The hydrogel constructed iRGD and GA-NPs exerted an effective anti-tumor effect possibly due to retention effect, local administration and continuous sustained release of iRGD promoting the penetration of nanoparticles into a deep part of tumors. The delivery system showed little systemic toxicity and would provide a promising strategy to improve anti-gastric cancer efficacy.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2018
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IF 3.909
Tsogzolmaa Ganbold,Shuqin Han,Agula Hasi,Huricha Baigude
Natural carbohydrate polymer-based nanoparticles have great biocompatibility that is required for the safe delivery of various drugs including nucleic acid therapeutics. Herein, we designed curdlan-based nanoparticles for cancer cell targeted delivery of short interfering RNA (siRNA). iRGD peptide conjugated 6-amino-6-deoxy curdlan specifically delivered siRNA to integrin expressing cancer cells. Incubation of cancer cells with free iRGD peptide competitively blocked cellular uptake of the iRGD functionalized curdlan nanoparticles. Chloroquine but not nystatin inhibited cellular uptake of iRGD functionalized curdlan nanoparticles, indicating that the iRGD peptide conjugated curdlan nanoparticles were internalized through the receptor (clathrin)-mediated endocytosis. Moreover, a disease related gene Plk1 was substantially knocked down by siRNA carried by 6AC-iRGD nanoparticles in HepG2 cells. Our data suggested that iRGD functionalized curdlan may provide a biocompatible carrier for siRNA delivery.
研究领域:
生物医学工程
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分子生物学
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药剂学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Yongchao Chu,Ning Chen,Huajun Yu,Hongjie Mu,Bin He,Hongchen Hua,Aiping Wang,Kaoxiang Sun
A nanoparticle (NP) was developed to target choroidal neovascularization (CNV) via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC) and transactivated transcription (TAT) (RKKRRQRRRC) peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. 1H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol)– poly(lactic-co-glycolic acid). The resulting particle size was 67.0±1.7 nm, and the zeta potential of the particles was −6.63±0.43 mV. The corneal permeation of iRGD and TAT NPs increased by 5.50- and 4.56-fold compared to that of bare and iRGD-modified NPs, respectively. Cellular uptake showed that the red fluorescence intensity of iRGD and TAT NPs was highest among primary NPs and iRGD- or TAT-modified NPs. CNV was fully formed 14 days after photocoagulation in Brown Norway (BN) rats as shown by optical coherence tomography and fundus fluorescein angiography analyses. Choroidal flat mounts in BN rats showed that the red fluorescence intensity of NPs followed the order of iRGD and TAT NPs > TAT-modified NPs > iRGD-modified NPs > primary NPs. iRGD and TAT dual-modified NPs thus displayed significant targeting and penetration ability both in vitro and in vivo, indicating that it is a promising drug delivery system for managing CNV via topical ocular administration.
研究领域:
药剂学
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眼科
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分子生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2016
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IF 7.145
Shengnan Ma,Jie Zhou,Yuxin Zhang,Yiyan He,Qian Jiang,Dong Yue,Xianghui Xu,Zhongwei Gu
The stability dilemma and limited tumor penetration of nanocarriers in cancer chemotherapy remain two predominant challenges for their successful clinical translation. Herein, the pH-sensitive fluorocarbon-functionalized nanocarriers (SFNs) with a tumor-homing and penetrating peptide iRGD are reported to overcome the stability dilemma and enhance tumor accumulation and penetration in an orthotopic breast cancer. The highly stable SFNs with a low critical association concentration provide a safe and spacious harbor for hydrophobic drugs. Furthermore, the stimulus-responsive evaluation and in vitro drug release study show that the SFNs can balance intracellular dissociation for drug release and extracellular stability in the blood circulation. Additionally, the tumor penetration capacity has been dramatically enhanced in 3D multicellular spheroids, effectively affecting cells far from the periphery. This can be ascribed to the coadministration of iRGD having tumor-penetrating ability and fluorocarbon chains having good cell membrane permeability. The combination of SFNs and iRGD is a viable approach to assist drugs’ effective accumulation in primary and metastasized tumor sites, significantly inhibiting the breast tumor growth and curbing lung and liver metastases in an orthotopic-tumor-bearing mouse model. Taken together, this pH-sensitive fluorinated nanosystem having excellent stability and tumor accumulation and penetration properties paves the way to combat cancer.
研究领域:
肿瘤学
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药剂学
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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
BIOMATERIALS
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2017
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IF 8.402
Yujie Su,Yahui Hu,Yu Wang,Xiangting Xu,Yang Yuan,Yunman Li,Zeyuan Wang,Kerong Chen,Fangrong Zhang,Xuefang Ding,Min Li,Jianping Zhou,Yuan Liu,Wei Wang
Multi-walled carbon nanotube (MWNT) with its versatility has exhibited tremendous superiority in drug delivery. Despite plenty of researches on MWNT based delivery systems, precision-guided assistances to maximize their profitable properties are still lacking in substantive progress. We developed here a dual-targeting and co-delivery system based on MWNT for antiangiogenesis therapy in lung cancer which aimed at renin-angiotensin system (RAS) dysregulation by synergistically conducting angiotensin II type 1 receptor (AT 1 R) and type 2 receptor (AT 2 R) pathway. In this work, iRGD peptide connected to polyethyleneimine (PEI) was linked to MWNT skeleton, accompanying with candesartan (CD) conjugated to MWNT mediated by cystamine (SS). The functionalized MWNT is assembled with plasmid AT 2 (pAT 2 ) to form iRGD-PEI-MWNT-SS-CD/pAT 2 complexes. iRGD and CD act as pilots for complexes to dually target symbolic ανβ3-integrin and AT 1 R both overexpressed on tumor angiogenic endothelium and lung cancer cell. CD as chemotherapy showed synergistic downregulation of VEGF when combining of pAT 2 and efficiently inhibited angiogenesis . iRGD-PEI-MWNT-SS-CD/pAT 2 complexes greatly appreciated drug activities by changing drug distribution and exhibited remarkable tumor growth suppression in A549 xenograft nude mice . Our work presents that such dual-targeting strategy highly improves the delivery performance of MWNT and open a new avenue for RAS related lung cancer therapy.
研究领域:
肿瘤学
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纳米医学
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药理学
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产品关联
DOI
PubMed
高影响因子
CHEMBIOCHEM
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2020
·Vol. 22
·期 7
·1302-1306
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IF 2.576
Chenyu Jiang,Fanyu Meng,Dongsheng Mao,Yuguo Tang,Peng Miao
Graphical Seeing dots and AuNPs : Tetrahedral DNA nanoconjugates have been constructed from DNA, peptides, gold nanoparticles and carbon nanodots. Target telomerase and miRNA can achieve strand displacement of corresponding DNA strands with quenched fluorescence reporters. The as-prepared biosystem is suitable for the simultaneous sensing and imaging of the dual biomarkers for diagnostics purposes. In this study, a tetrahedral DNA nanostructure was first self-assembled; this was then conjugated with gold nanoparticles (AuNPs) and carbon nanodots (CDs). The fabricated nanocomposites allow simultaneous analysis of telomerase activity and miRNA with dual fluorescence channels. By further introducing an iRGD peptide sequence, the nanoconjuates can be conveniently transferred inside living cells for in situ imaging. The analytical performances and anti-jamming capabilities are excellent. Meanwhile, the materials are highly biocompatible for intracellular applications. Therefore, the proposed biosystem shows great promise as a powerful tool for quantitative analysis of the dual biomarkers. The strategy can also be further exploited as a versatile platform for in situ detection of many other targets for early disease diagnosis.
研究领域:
生物化学
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纳米技术
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分子生物学
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癌症诊断
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产品关联
DOI
PubMed
高影响因子
Translational Lung Cancer Research
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2024
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IF 4
Yunlong Li,Chenmei Li,Jiamin Li,Dong Han,Gang Xu,Daolong Zhu,Huiming Cai,Yiqing Wang,Dong Wang
Background Accurate real-time tumor delineation is essential for achieving curative resection (R0 resection) during non-small cell lung cancer (NSCLC) surgery. The unique characteristics of lung tissue structure significantly challenge the use of video-assisted thoracoscopic surgery in the identification of lung nodules. This difficulty often results in an inability to discern the margins of lung nodules, necessitating either an expansion of the resection scope, or a transition to open surgery. Due to its high spatial resolution, ease of operation, and capacity for real-time observation, near-infrared fluorescence (NIRF) navigation in oncological surgery has emerged as a focal point of clinical research. Targeted NIRF probes, which accumulate preferentially in tumor tissues and are rapidly cleared from normal tissues, enhance diagnostic sensitivity and surgical outcomes. The imaging effect of the clinically approved NIRF probe indocyanine green (ICG) varies significantly from person to person. Therefore, we hope to develop a new generation of targeted NIRF probes targeting lung tumor-specific targets. Methods First, the peptide iRGD (sequence: CRGDKGPDC) fluorescent tracer was synthesized, and characterized through mass spectrometry (MS), proton nuclear magnetic resonance ( 1 H NMR), and high-performance liquid chromatography (HPLC). Fluorescence properties were tested subsequently. Safety was performed in vitro using both human normal liver cells and human normal breast cells. Second, Metabolism and optimal imaging time were determined by tail vein injection of iRGD fluorescent tracer. Finally, Orthotopic and metastatic lung tumor models were used to evaluate the targeting properties of the iRGD fluorescent tracer. Results We successfully synthesized an iRGD fluorescent tracer specifically designed to target NSCLC. The molecular docking analyses indicated that this tracer has receptor affinity comparable to that of iRGD for αvβ3 integrin, with a purity ≥98%. Additionally, the tracer is highly soluble in water, and its excitation and emission wavelengths are 767 and 799 nm, respectively, positioning it within the near-infrared spectrum. The cellular assays confirmed the tracer’s minimal cytotoxicity, underscoring its excellent biosafety profile. In vivo studies further validated the tracer’s capacity for specific NSCLC detection at the cellular level, alongside a prolonged imaging window of 6 days or more. Notably, the tracer demonstrated superior specificity in localizing very small lung nodules, which are otherwise clinically indiscernible, outperforming non-targeted ICG. Fluorescence intensity analyses across various organs revealed that the tracer is predominantly metabolized by the liver and kidneys, with excretion via bile and urine, and exhibits minimal toxicity to these organs as well as the lungs. Conclusions The iRGD fluorescent tracer selectively accumulates in NSCLC tissues by specifically targeting αvβ3 receptors, which are overexpressed on the surface of tumor cells. This targeted approach facilitates the real-time intraoperative localization of NSCLC, presenting an improved strategy for intraoperative tumor identification with significant potential for clinical application. Click here to view. (86K, pdf)
研究领域:
肿瘤学
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生物医学工程
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药学
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分子生物学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2017
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IF 4.3
Fei Gao,Jinming Zhang,Chaomei Fu,Xiaoming Xie,Fu Peng,Jieshu You,Hailin Tang,Zhiyu Wang,Peng Li,Jianping Chen
Isoliquiritigenin (ISL), a natural anti-breast cancer dietary compound, has poor delivery characteristics and low bioavailability. In order to promote the therapeutic outcome of ISL, a tumor-targeting lipid–polymer hybrid nanoparticle (NP) system modified by tumor-homing iRGD peptides has been developed. The hybrid NPs were prepared by a modified single-step nanoprecipitation method to encapsulate ISL. iRGD peptides were anchored on the surface by a postinsertion method (ISL-iRGD NPs). The stable lipid–polymer structure of ISL-iRGD NPs, with high encapsulation and loading efficiency, was confirmed. Compared to free ISL and non-iRGD-modified counterparts, ISL-iRGD NPs showed higher cytotoxicity and cell apoptosis against the different type of breast cancer cells. This was attributable to higher cellular accumulation mediated by the iRGD-integrin recognition and the nanoscale effect. More importantly, based on the active tumor-tissue accumulation by iRGD peptides and the prolonged in vivo circulation by the stealth nanostructure, ISL-iRGD NPs displayed higher tumor-growth inhibition efficiency in 4T1-bearing breast-tumor mouse models. Therefore, the constructed iRGD modified lipid–polymer hybrid NPs would provide a promising drug-delivery strategy to improve ISL in anti-breast cancer efficacy.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2025
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IF 11.9
Zhiyuan Tang,Yuening Sun,Quanhua Yi,Qian Ding,Yang Ding,Jianfei Huang
The effective intracellular accumulation of doxorubicin (DOX) is crucial for improving antitumor efficacy, which is severely impeded by limited drug penetration, uncontrollable drug release, and drug resistance. In this study, a thermal-deformative polymer embedding ultrasmall ceria (CeO 2 ) was rationally designed for deep tumor drug shuttling and hypoxia reversal to improve chemotherapy. Structurally, the CeO 2 nanozyme was covalently grafted with a polymer of p(NIPAM-co-AM) that could sharply shrink for DOX loading, which was consolidated with polydopamine (PDA) film encapsulation. Thereafter, a tumor penetration guide of apolipoprotein A-I (apoA-I) conjugated iRGD peptide (apoA-I-iRGD) was further decorated onto the PDA shell via Michael addition for preparing CeO 2 P/DOX@iAPDA. With the aid of apoA-I-iRGD, CeO 2 P/DOX@iAPDA penetrated both the tumor spheroids (∼78 μm) and the tumors of the mouse model deeply. After internalization by tumor cells and triggering by low pH in lysosomes, rapid DOX release was achieved by peeling off the PDA shell and thermosensitive deformation of p(NIPAM-co-AM). CeO 2 P/DOX@iAPDA provided 66.4% tumor suppression in 4T1-derived tumor spheroids and 63.2% in 4T1-tumor-bearing mice, respectively. Preliminary mechanistic research involving western blotting and immunohistochemistry revealed that CeO 2 P/DOX@iAPDA reversed resistance through the through HIF-1α-P-gp/lipid axis. Collectively, this study intelligently integrated CeO 2 nanozymes, temperature-sensitive polymers, and imitated biochemical modifications to improve chemotherapy for breast cancer.
研究领域:
纳米技术
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癌症治疗
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药学科学
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生物医学工程
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分子生物学
✓ 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）