ADVANCED FUNCTIONAL MATERIALS
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2018
·Vol. 28
·期 32
·1802281
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IF 13.325
Chen Bai,Zhengyang Jia,Lina Song,Wei Zhang,Yi Chen,Fengchao Zang,Ming Ma,Ning Gu,Yu Zhang
To achieve the accurate diagnosis of tumor with the magnetic resonance imaging (MRI), nanomaterials-based contrast agents are developed rapidly. Here, a tumor targeting nanoprobe of c(RGDyK) modified ultrasmall sized iron oxide is reported with high saturation magnetization and high T 1 -weighted imaging capability, attributed to a large number of paramagnetic centers on the surface of nanoprobes and rapid water proton exchange rate (inner sphere model), as well as strong superparamagnetism (outer sphere model). These nanoprobes could actively target and gradually accumulate at the tumor site with a time-dependent T 1 –T 2 contrast enhancement imaging effect. In in vivo MRI experiments, the nanoprobes exhibit the best T 1 contrast enhancement at 30 min after intravenous administration, followed by gradually vanishing and generating T 2 contrast enhancement with increasing time at tumor site. This is likely due to time-dependent nanoprobes aggregation in tumor, in good agreement with in vitro experiment where aggregated nanoprobes display larger r 2 / r 1 value (19.1) than that of the dispersed nanoprobes (2.8). This dynamic property is completely different from other T 1 -T 2 dual-modal nanoprobes which commonly exhibit the T 1 - and T 2 -weighted enhancement effect at the same time. To sum up, these c(RGDyK) modified ultrasmall Fe 3 O 4 nanoprobes have significant potential to improve the diagnostic accuracy and sensitivity in MRI.
研究领域:
生物医学工程
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纳米医学
·
影像诊断学
✓ 已验证
DOI
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2019
·
IF 4.462
Qi-Long Wu,He-Lin Xu,Cui Xiong,Qing-Hua Lan,Ming-Ling Fang,Jin-Hua Cai,Hui Li,Shu-Ting Zhu,Jing-Hong Xu,Fang-Yi Tao,Cui-Tao Lu,Ying-Zheng Zhao,Bin Chen
Surgical resection remains the preferred approach for some patients with glioblastoma (GBM), and eradication of the residual tumour niche after surgical resection is very helpful for prolonging patient survival. However, complete surgical resection of invasive GBM is difficult because of its ambiguous boundary. Herein, a novel targeting material, c(RGDyk)-poloxamer-188, was synthesized by modifying carboxyl-terminated poloxamer-188 with a glioma-targeting cyclopeptide, c(RGDyk). Quantum dots (QDs) as fluorescent probe were encapsulated into the self-assembled c(RGDyk)-poloxamer-188 polymer nanoparticles (NPs) to construct glioma-targeted QDs-c(RGDyk)NP for imaging-guided surgical resection of GBM. QDs-c(RGDyk)NP exhibited a moderate hydrodynamic diameter of 212.4 nm, a negative zeta potential of –10.1 mV and good stability. QDs-c(RGDyk)NP exhibited significantly lower toxicity against PC12 and C6 cells and HUVECs than free QDs. Moreover, in vitro cellular uptake experiments demonstrated that QDs-c(RGDyk)NP specifically targeted C6 cells, making them display strong fluorescence. Combined with ultrasound-targeted microbubble destruction (UTMD), QDs-c(RGDyk)NP specifically accumulated in glioma tissue in orthotropic tumour rats after intravenous administration, evidenced by ex vivo NIR fluorescence imaging of bulk brain and glioma tissue sections. Furthermore, fluorescence imaging with QDs-c(RGDyk)NP guided accurate surgical resection of glioma. Finally, the safety of QDs-c(RGDyk)NP was verified using pathological HE staining. In conclusion, QDs-c(RGDyk)NP may be a potential imaging probe for imaging-guided surgery.
研究领域:
医学影像学
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肿瘤学
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纳米医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Jinyang Li,Zhilan Chai,Jiasheng Lu,Cao Xie,Danni Ran,Songli Wang,Jianfen Zhou,Weiyue Lu
Owing to the binding capacity to ɑ v β 3 integrin overexpressed on glioma, vasculogenic mimicry and neovasculature, the peptide c(RGDyK) has been exploited pervasively to functionalize nanocarriers for targeted delivery of bioactives. The former study in our group substantiated the immunotoxicity of c(RGDyK)-modified liposome , and this unfavorable immunogenicity is known to compromise blood circulation, targeting efficacy and therapeutic outcome. Therefore, we need to find a superior alternative ligand in order to evade the exquisite immuno-sensitization. We developed mn by structure-guided peptide design and retro-inverso isomerization technique, which was experimentally substantiated to have exceptional binding affinity to ɑ v β 3 integrin. Besides mn does not have affinity toward normal liver cells and kidney cells, which c(RGDyK) possesses in a certain degree. Warranting that mn and c(RGDyK) anchored ɑ v β 3 , we formulated peptide-tethered liposomes and investigated in vivo bio-fate. Compared with c(RGDyK)-modified liposome, mn-modified liposome presented longer blood circulation and reduced ingestion by Kupffer cells with decreased retention in liver accordingly, benefitting from attenuated anti-liposome IgG and IgM response elicited by multiple sequential doses. Those merits strengthened the anti-glioma efficacy of ɑ v β 3 -targeted doxorubicin-loaded liposomes, proving the importance of immunocompatibility in process of targeted drug delivery .
研究领域:
药理学
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肿瘤学
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分子生物学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2016
·
IF 8.854
Weidong Gao,Zhaohui Wang,Liwei Lv,Deyan Yin,Dan Chen,Zhihao Han,Yi Ma,Min Zhang,Man Yang,Yueqing Gu
Photodynamic therapy (PDT) has recently emerged as an approach to enhance intratumoral accumulation of nanoparticles. However, conventional PDT is greatly limited by the inability of the excitation light to sufficiently penetrate tissue, rendering PDT ineffective in the relatively deep tumors. To address this limitation, we developed a novel PDT platform and reported for the first time the effect of deep-tissue PDT on nanoparticle uptake in tumors. This platform employed c(RGDyK)-conjugated upconversion nanoparticles (UCNPs), which facilitate active targeting of the nanoconstruct to tumor vasculature and achieve the deep-tissue photosensitizer activation by NIR light irradiation. Results indicated that our PDT system efficiently enhanced intratumoral uptake of different nanoparticles in a deep-seated tumor model. The optimal light dose for deep-tissue PDT (34 mW/cm 2 ) was determined and the most robust permeability enhancement was achieved by administering the nanoparticles within 15 minutes following PDT treatment. Further, a two-step treatment strategy was developed and validated featuring the capability of improving the therapeutic efficacy of Doxil while simultaneously reducing its cardiotoxicity. This two-step treatment resulted in a tumor inhibition rate of 79% compared with 56% after Doxil treatment alone. These findings provide evidence in support of the clinical application of deep-tissue PDT for enhanced nano-drug delivery.
研究领域:
癌症治疗
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纳米医学
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生物医学工程
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药学科学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2016
·Vol. 5
·期 12
·1447-1461
·
IF 5.76
Fatima Zohra Dahmani,Yan Xiao,Juan Zhang,Yao Yu,Jianping Zhou,Jing Yao
Combination of antiangiogenesis and chemotherapy holds vast promise for effective inhibition of tumor proliferation and invasion. Herein, a multifunctional self-assembled nanosystem consisting of amphiphilic c(RGDyK)-functionalized low-molecular-weight heparin–gambogic acid conjugate (cRHG) is developed, using c(RGDyK) peptide as α v β 3 integrin targeting moiety to realize a double-targeted delivery to both tumor cells and angiogenic vasculature. cRHG with a markedly decreased anticoagulant activity can self-assemble into nanosized particles (around 150 nm). cRHG nanoparticles effectively inhibit vascular endothelial growth factor (VEGF)-triggered tube-like formation of HUVEC and neovascularization of subcutaneous Matrigel plugs. More importantly, the targeting ability of cRHG nanoparticles is revealed by their efficient internalization by α v β 3 integrin-positive cells (U87MG and HUVEC) in vitro and obvious accumulation of Cy7/cRHG in the tumor site with strong fluorescence signals in both cancer cells and neovasculature. Besides, cRHG maintains the in vitro cytotoxic activity of gambogic acid, while achieving the highest in vivo antitumor activity in U87MG mouse xenograft model and displaying better safety profile than free drugs solutions. Mechanistic investigations reveal the substantial inhibition of hypoxia-inducible factor-1 alpha, VEGF, and CD31 expression by cRHG nanoparticles with remarkable down-regulation of VEGFR2 phosphorylation. These results suggest that cRHG nanoparticles provide a versatile nanoplatform for efficacious combinatorial tumor therapy.
研究领域:
纳米医学
·
癌症治疗
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药学科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Minglong Chen,Bin Chen,Xiaoguang Ge,Qingjie Ma,Shi Gao
One of the main reasons why most cancer patients do not respond well to chemotherapy is that drugs cannot accumulate in tumors at an optimal dose, eventually resulting in failure to prevent cancer cell growth. To improve drug delivery efficiency, we engineered a highly efficient tumor-targeted and stroma-breaking nanocarrier by the modification of iron oxide nanoparticles (IONPs) with a tumor-targeting peptide c(RGDyK) and a hyaluronidase (HAase) on the surface. The yielding nanocomplex, c(RGDyK)-HAase-IONP, targeted the tumor by binding integrin αvβ3 and went deeply into the tumors by the degradation of hyaluronic acid (HA), which was highly expressed in the tumor extracellular matrix (ECM). Good biostability and a low pH preferred drug release profile were characterized for c(RGDyK)-HAase-IONP carrying DOX in vitro. c(RGDyK)-HAase-IONP showed an improved tumor-targeting (2.5 times higher) effect after intravenous injection in the MC38 tumor-bearing mice model, as determined by whole-body fluorescence imaging compared to the non-targeted IONPs without HAase. After 5 systemic treatments, c(RGDyK)-HAase-IONP/DOX (5 mg/kg of equivalent dose of DOX) significantly inhibited MC38 tumor growth (22.1 ± 7.4 times relative to the non-treated group). Elevated apoptosis and reduced proliferation in the tumor cell were detected in the c(RGDyK)-HAase-IONP/DOX treated tumors compared to the control groups. Overall, the highly efficient targeted nanocarrier c(RGDyK)-HAase-IONP demonstrated tremendous potency for improving drug delivery and tumor therapy efficacy by targeted degradation of the dense HA barrier in the tumor ECM. We determined that such a tumor stroma–degrading nanosystem was capable of reducing tumor recurrence and drug resistance and could ultimately improve clinical tumor treatment responses.
研究领域:
癌症治疗
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
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