TUMOR BIOLOGY
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2016
·Vol. 37
·期 7
·8609-8619
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IF 2.926
Xu Jinfeng,Zeng Xinxin,Liu Yingying,Luo Hui,Wei Zhanghong,Liu Huiyu,Zhou Yuli,Zheng Hairong,Zhou Jie,Tan Guanghong,Yan Fei
Ultrasound-targeted microbubble destruction (UTMD) has become a novel gene/drug delivery method in cancer therapeutic application. However, the gene transfection efficiency mediated by UTMD is still unsatisfactory. Here, we introduced iRGD/CCR2 dual-targeted cationic microbubbles (MB iRGD/CCR2 ) which was modified with PEI-600 and coated with iRGD peptides and anti-CCR-2 antibodies. It showed that MB iRGD/CCR2 had a 25.83 ± 1.57 mV surface zeta potential and good stability. The experiments in vitro showed MB iRGD/CCR2 had higher binding efficiency with both bEnd.3 cells and MCF-7 cells than that of iRGD or CCR2 single-targeted cationic microbubbles (MB iRGD or MB CCR2 ) ( P < 0.05 for both). Agarose gel electrophoresis assay showed that MB iRGD/CCR2 can effectively load pGPU6/GFP/Neo-shAKT2 plasmid DNA. Compared with the plain MBs (MB control ) or single-targeted cationic MBs including MB iRGD and MB CCR2 ( P < 0.05 for all), the dual-targeted cationic MB iRGD/CCR2 groups had higher gene transfection efficiency under US exposure. It showed that the dual-targeted cationic MB iRGD/CCR2 has a potential value to be used as an ultrasound imaging probe for ultrasound image-guided tumor gene therapy.
研究领域:
医学影像
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基因治疗
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癌症研究
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超声技术
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PubMed
高影响因子
Stem Cell Research & Therapy
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2026
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IF 7.8
Li Xiao-huan,Lian Fu-wei,Lv Feng,Luo Xiao-Ling,Hu Bang-li,Zhang Li-tu,Ning Shu-fang
Background Mesenchymal stem cells (MSCs)-derived exosomes present great potential as nanocarriers for targeted drug delivery. Moreover, the therapeutic efficacy of exosomes can be substantially enhanced through functional modifications and the incorporation of bioactive molecules. Methods In this study, the MSCs were cultured under two-dimensional (2D) and three-dimensional (3D) cell culture conditions. The culture supernatants were collected for isolating exosomes. The characteristics and yields of exosomes from 2D and 3D cultures were detected by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), western blot analysis, and bicinchoninic acid (BCA) assay. Subsequently, 3D exosomes were loaded with miR-99b-5p and modified with iRGD peptide were formed into a new engineered exosome, designated as iRGD-Exo-miR-99b-5p. The effects of these engineered exosomes on the progression of colorectal cancer (CRC) were assessed through a series of in vivo and in vitro experiments. Results The 3D-cultured MSCs exhibited a higher yield of exosomes and enhanced uptake by CRC cells. Further in vitro experiments demonstrated that 3D-exosomes loaded with miR-99b-5p effectively inhibit the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of CRC cells. Results from a xenograft tumor model indicate that iRGD-modified exosomes were significantly enriched at tumor sites. Furthermore, exosomes modified with iRGD and loaded with miR-99b-5p were employed for CRC treatment, resulting in substantial tumor growth inhibition and enhanced the chemotherapy efficacy of 5-fluorouracil (5-FU) in vivo, without inducing notable toxicity or side effects. Mechanistically, exosome-mediated delivery of miR-99b-5p downregulated FGFR3 expression, thereby inhibiting the activation of the PI3K/AKt signaling pathway and promoting ferroptosis, ultimately attenuating CRC progression. Conclusions Collectively, iRGD-modified 3D exosomes loaded with miR-99b-5p were able to specifically target tumor sites, thereby significantly suppressing CRC growth through the induction of ferroptosis via regulating the FGFR3/PI3K/AKt signaling pathway. These findings suggest that functional engineering and bioactive loading of 3D-exosomes derived from MSCs represent a promising strategy for targeted cancer therapy. Graphical
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Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Ziting Zhang,You Ji,Nan Hu,Qinqi Yu,Xinrui Zhang,Jie Li,Fenglei Wu,Huae Xu,Qiyun Tang,Xiaolin Li
Ferroptosis is a novel form of programmed cell death impelled by iron-dependent lipid peroxidation, which may be a potential strategy for cancer therapy. Here we demonstrated for the first time that Resveratrol (RSV), a traditional Chinese medicine (TCM) chemical monomer, could effectually inhibit the growth of colon cancer cells through the ROS-dependent ferroptosis pathway. Mechanistically, RSV evoked the increase of reactive oxygen species and lipid peroxidation in colorectal cancer cells, and eventually lead to ferroptosis. Furthermore, RSV could promote ferroptosis by downregulating the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). To improve the delivery efficiency of RSV, a biomimetic nanocarrier was developed by coating RSV-loaded poly(ε-caprolactone)–poly(ethylene glycol) (PCL-PEG) nanoparticles with erythrocyte membrane ( [email protected] ). The [email protected] provide the possibility to escape macrophage phagocytosis and have a long circulation effect. In addition, when coupled with a tumor-penetrating peptide iRGD, which could trigger enhanced tissue penetration tumor-specifically, the delivery of [email protected] into tumors would be significantly improved results from the in vivo study demonstrated an excellent treatment efficacy for CRC. Altogether, our study highlighted the therapeutic potential of RSV as a ferroptosis-inducing anticancer agent and when loaded into a biomimetic nanoplatform, it might pave the way for the application of RSV loaded nanosystems for colorectal cancer treatment.
研究领域:
肿瘤学
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药理学
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纳米技术
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生物医学工程
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PubMed
高影响因子
Advanced Healthcare Materials
·
2021
·Vol. 10
·期 16
·2100536
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IF 9.933
Honglan Wang,Jiyuan Zhou,Ying Fu,Yuzhao Zheng,Weiyang Shen,Jianping Zhou,Tingjie Yin
A limited infiltration and the subsequent low effective drug concentration result in poor chemotherapeutic outcomes against tumors, and even further promote tumor resistance and metastatic. Herein, iRGD-modified graphene oxide (GO) nanosheets (IPHG) are developed for the intensive treatment of metastatic tumors using focus-specific penetrated delivery together with photothermal therapy-mediated chemosensitization and photothermal therapy-strengthened integrin targeting-based antimigration. In vitro and in vivo data verified the mechanism of the tumor-selective infiltration of IPHG is based on a rigid 2D structure-associated advantage regarding hemodynamics and endothelial contact, followed by iRGD-endowed transendothelial and intratumoral transport. Once IPHG-DOX-penetrated 4T1 tumors are exposed to near-infrared irradiation, hyperthermia stress and photothermal therapy-elevated effective drug concentrations result in chemosensitization and prominent tumor suppression. Meanwhile, the specific binding of iRGD to integrins and photothermal therapy leads to the synergistic perturbation of cytoskeleton remodeling and subsequent impairment of cell motility and metastasis. The tailored design of IPHG validates a promising paradigm for drug delivery to combat tumor resistance and metastasis resulting from poor target access for single chemotherapy.
研究领域:
肿瘤学
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纳米技术
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治疗学
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药物递送系统
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PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Yanhong Liu,Lingchao Li,Jiyong Liu,Mengnan Yang,Honglan Wang,Xuxin Chu,Jianping Zhou,Meirong Huo,Tingjie Yin
The complex blood environment, heterogenic enhanced permeability and retention (EPR) effect, and dense matrix comprise the primary “leakage obstacles” impeding specific accumulation and penetration of nanodrugs against solid tumors, thus forming a key bottleneck for their clinical application. Herein, we present a biomineralization-inspired dasatinib (DAS) nanodrug (CIPHD/DAS) that sequentially permeates all of the abovementioned hindrances for efficient treatment of solid tumors. CIPHD/DAS exhibited a robust hybrid structure constructed from an iRGD-modified hyaluronic acid-deoxycholic acid organic core and a calcium phosphate mineral shell. In vitro and in vivo data demonstrated the mechanism of sequential tumoral infiltration was based on mineral-stiffened blood circulation with decreased premature drug leakage, iRGD-endowed tumor-specific transendothelial transport for “first-order promotion of accumulation” and DAS-mediated restoration of fibrotic stromal homeostasis for “second-order promotion of penetration”. Resultantly, CIPHD/DAS showed remarkable distal drug availability in desmoplastic 4T1/CAFs orthotropic mouse models and significantly suppressed tumor growth and metastasis. This optimized strategy with sequential permeabilization of the capital “leakage obstacles” validates a promising paradigm to conquer the “impaired delivery and penetration” associated bottleneck of nanodrugs in the clinical treatment of solid tumors.
研究领域:
癌症研究
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药学
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材料科学
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生物医学工程
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PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Zhen Wang,Hao Cheng,Yu Sheng,Zongkai Chen,Xiaohong Zhu,Jianye Ren,Xiangze Zhang,Lingyu Lv,Huaqing Zhang,Jianping Zhou,Yang Ding
Biofunctional surface-modification surpassed critical limitation of graphene oxide (GO) in biocompatibility and drug delivery efficiency, contributing to versatile biomedical applications . Here, a protein corona-bridged GO nanoplatform with high drug loading, longstanding hyperthermia, and controllable drug release, was engineered for amplified tumor therapeutic benefits. Structurally, GO surface was installed with phenylboronic acid (PBA) layer, on which iRGD conjugated apolipoprotein A-I (iRGD-apoA-I) was coordinated via boron electron-deficiency, to form the sandwich-like GO nanosheet (iAPG). The GO camouflaging by iRGD-apoA-I corona provided multimodal high doxorubicin (DOX) loading by π-π stacking and coordination, and generated a higher photothermal transformation efficiency simultaneously. In vitro studies demonstrated that iAPG significantly improved drug penetration and internalization , then achieved tumor-targeted DOX release through near-infrared (NIR) controlled endo/lysosome disruption. Moreover, iAPG mediated site-specific drug shuttling to produce a 3.53-fold enhancement of tumor drug-accumulation compared to the free DOX in vivo , and induced deep tumor penetration dramatically. Primary tumor ablation and spontaneous metastasis inhibition were further demonstrated with negligible side effects under optimal NIR. Taken together, our work provided multifunctional protein corona strategy to inorganic nanomaterials toward advantageous biomedical applications.
研究领域:
生物医学工程
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纳米技术
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癌症治疗
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药物递送系统
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PubMed
高影响因子
CHEMBIOCHEM
·
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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PubMed
高影响因子
DRUG DELIVERY
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2021
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IF 6.419
Jiachi Ma,Yuzhong Chen,Wanqing Liang,Lei Li,Jun Du,Chengwu Pan,Chensong Zhang
Gastric cancer (GC) remains a major public health problem. Ursolic acid (UA) is reported to be effective in inhibiting GC; however, its low solubility and poor biocompatibility have greatly hindered its clinical application. Herein, an innovative reactive oxygen species (ROS)-sensitive UA dimeric prodrug is developed by coupling two UA molecules via a ROS-cleavable linkage, which can self-assemble into stable nanoparticles in the presence of surfactant. This new UA-based delivery system comprises the following major components: (I) dimeric prodrug inner core that can achieve high drug-loading (55%, w/w) and undergo rapid and selective conversion into intact drug molecules in response to ROS; (II) a polyethylene glycol (PEG) shell to improve colloid stability and extend blood circulation, and (III) surface-modified internalizing RGD (iRGD) to increase tumor targeting. Enhancement of the antitumor effect of this delivery system was demonstrated against GC tumors in vitro and in vivo. This novel approach offers the potential for clinical applications of UA.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Gongxin Yang,Jikai Xia,Xiaoqing Dai,Hongbo Zhao,Weiqing Gao,Weilong Ding,Xiaofeng Tao,Ling Zhu
Introduction Magnetic resonance imaging (MRI) is an important tool for the accurate diagnosis of malignant tumors in clinical settings. However, the lack of tumor-specific MRI contrast agents limits diagnostic accuracy.Methods Herein, we developed αv integrin receptor-targeting multi-crystalline manganese oxide (MCMO) as a novel MRI contrast agent for accurate diagnosis of tumors by coupling iRGD cyclopeptide PEGylation polymer onto the surface of MCMO (iRGD-pMCMO).Results The MCMO consisted of numerous small crystals and exhibited an oval structure of 200 nm in size. The iRGD-pMCMO actively recognizes tumor cells and effectively accumulates at the tumor site, consequently releasing abundant Mn2+ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn2+ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T1-weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T1-weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T1 contrast effect of iRGD-pMCMO was closely associated with the expression of GSH in tumor cells.Conclusion Altogether, the novel tumor-targeting, highly sensitive MRI contrast agent developed in this study can improve the accuracy of MRI for tumor diagnosis.
研究领域:
医学影像
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纳米技术
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癌症诊断
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材料科学
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
·
IF 10.5
Miao Tang,Yu Xin,Yunchun Zhao,Xiao Zhang,Meng Zhang,Dongli Sun,Xiaojun Zhu,Yao Yao,Weidong Fei,Caihong Zheng
Physiological or pathological hypoperfusion of the placenta is one of the main causes of intrauterine growth restriction (IUGR) which poses a significant risk to the health of the fetus and newborn. Tadalafil, a 5-type phosphodiesterase inhibitor, has previously been found to improve the symptoms of IUGR in various clinical studies. Unfortunately, its clinical utility is hindered by its limited water solubility, rapid metabolism, and lack of specific distribution in target tissues rendering tadalafil unable to maintain long-term placental perfusion. In this study, iRGD-modified tadalafil-loaded liposomes (iRGD-lipo@Tad) featuring a size of approximately 480 nm were designed to rectify the shortcomings of tadalafil. The prepared iRGD-lipo@Tad exhibited superior stability, sustained drug release capacity, and low cytotoxicity. The fluorescence study, tissue slice study, and drug biodistribution study together demonstrated the placenta-anchored ability of iRGD-modified liposomes. This was achieved by a dual approach consisting of the iRGD-mediated placenta-targeting effect and special particle size-mediated placenta resident effect. The pharmacokinetic study revealed a significant improvement in the in vivo process of tadalafil encapsulated by the iRGD-modified liposomes. In comparison to the tadalafil solution, the peak plasma concentration of iRGD-lipo@Tad was significantly increased, and the area under the curve was increased by about 7.88 times. In the pharmacodynamic study, iRGD-lipo@Tad achieved a continuous and efficient improvement of placental blood perfusion. This was achieved by decreasing the ratio of plasma soluble fms-like tyrosine kinase to placental growth factor and increasing the levels of cyclic guanosine monophosphate and nitric oxide. Consequently, iRGD-lipo@Tad resulted in a significant increase in embryo weight and a reduction in the miscarriage rate of N-Nitro-L-arginine methyl ester-induced IUGR pregnant mice without detectable toxicity. In summary, the nanotechnology-assisted therapy strategy presented here not only overcomes the limitations of tadalafil in the clinical treatment of IUGR but also offers new avenues to address the treatment of other placenta-originated diseases.
研究领域:
药理学
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妇产科学
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纳米技术
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生物医学工程
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生殖医学
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高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 41
·期 4
·525-537
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IF 3.815
Zhou Meng-Xue,Zhang Jia-Yu,Cai Xiao-Meng,Dou Rui,Ruan Li-Fo,Yang Wen-Jiang,Lin Wen-Chu,Chen Jun,Hu Yi
As one of the major challenges in tumor chemotherapy, multidrug resistance typically correlates with the poor drug penetration within tumor tissues and drug efflux by the ATP-driven efflux pumps in tumor cells. Herein, we design a kind of near-infrared (NIR) light- and acidity-activated micellar iPUTDN nanoparticle for mitochondria-targeting doxorubicin (DOX) delivery to combat DOX resistance in small-cell lung cancer. While the PEGylated iPUTDN nanoparticles can keep stealth in blood circulation, NIR irradiation at the tumor region can peel off the PEG shell from the nanoparticles, and the exposed iRGD can facilitate deep tumor penetration of the nanoparticles. After being internalized by DOX-resistant H69AR cells, the poly(β-aminoester)s (PAE)-based nanoparticles can release the triphenylphosphonium (TPP)-conjugated DOX (TDOX) into the cytosol, which can further accumulate in mitochondria with the aid of TPP. Consequently, the mitochondrial membrane potential and ATP content are both reduced in DOX-resistant H69AR cells. The in vivo therapeutic results show that TDOX-loaded nanoparticles with the aid of NIR light irradiation can effectively suppress the DOX-resistant small-cell lung cancer without noticeable adverse effects.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症研究
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高影响因子
Small
·
2020
·Vol. 17
·期 5
·2006582
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IF 11.459
Cheng-Yuan Dong,Sheng Hong,Di-Wei Zheng,Qian-Xiao Huang,Fu-Sheng Liu,Zhen-Lin Zhong,Xian-Zheng Zhang
Glioblastoma is the most common lethal malignant intracranial tumor with a low 5-year survival rate. Currently, the maximal safe surgical resection, followed by high-dose radiotherapy (RT), is a standard treatment for glioblastoma. However, high-dose radiation to the brain is associated with brain injury and results in a high fatality rate. Here, integrated pharmaceutics (named D-iGSNPs) composed of gold sub-nanometer particles (GSNPs), blood-brain barrier (BBB) penetration peptide iRGD, and cell cycle regulator α-difluoromethylornithine is designed. In both simulated BBB and orthotopic murine GL261 glioblastoma models, D-iGSNPs are proved to have a beneficial effect on the BBB penetration and tumor targeting. Meanwhile, data from cell and animal experiments reveal that D-iGSNPs are able to sensitize RT. More importantly, the synergy of D-iGSNPs with low-dose RT can exhibit an almost equal therapeutic effect with that of high-dose RT. This study demonstrates the therapeutic advantages of D-iGSNPs in boosting RT, and may provide a facile approach to update the current treatment of glioblastoma.
研究领域:
肿瘤学
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纳米技术
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药剂学
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神经科学
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高影响因子
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