Mingming Zhen

Preparation of Pd-decorated fullerenols on carbon nanotubes with excellent electrocatalytic properties in alkaline media

Pd-modified fullerenol (Pd-F) composite nanoparticles (NPs) are obtained through an in situ reduction method. These Pd-F composite NPs loaded on CNTs exhibit competitive electrocatalytic activity and outstanding stability for methanol oxidation in alkaline solution, which indicate that the fullerenols in the composite catalyst play an important role in the catalytic process.

A highly efficient and tumor vascular-targeting therapeutic technique with size-expansible gadofullerene nanocrystals

It has long been a dream to achieve tumor targeting therapy that can efficiently reduce the toxicity and severe side effects of conventional antitumor chemotherapeutic agents. Taking advantage of the abnormalities of tumor vasculature, we demonstrate here a new powerful tumor vascular-targeting therapeutic technique for solid cancers that applies advanced nanotechnology to cut off the nutrient supply of tumor cells by physically destroying the abnormal tumor blood vessels. Water soluble magnetic Gd@C82 nanocrystals of the chosen sizes are deliberately designed with abilities to penetrate into the leaky tumor blood vessels. By triggering the radiofrequency induced phase transition of gadofullerene nanocrystals while extravasating the tumor blood vessel, the explosive structural change of nanoparticles generates a devastating impact on abnormal tumor blood vessels, resulting in a rapid and extensive ischemia necrosis and shrinkage of the tumors. This unprecedented target-specific physiotherapy is found to work perfectly for advanced and refractory solid tumors.中文摘要本文报道了一种利用金属富勒烯纳米晶体快速高效治疗肿瘤的新技术. 从生物学上肿瘤血管和正常血管在结构上存在显著差异这一特点着手, 利用材料学上金属富勒烯纳米晶体在吸收射频能量后发生相变, 伴随着体积剧烈膨胀的特性, 高选择性地摧毁肿瘤血管. 研究表明, 经过1小时治疗后, 肿瘤部位血流即可发生快速阻断, 治疗2~4小时后, 肿瘤组织逐步发生出血性坏死, 肿瘤塌陷体积缩小; 并且对于多种实体肿瘤均有显著疗效. 该技术是一种快速、广谱、特异性高、毒副作用小的新型肿瘤治疗技术, 是一种具有巨大发展潜力的肿瘤治疗技术.

Amphiphilic trismethylpyridylporphyrin-fullerene (C70) dyad: an efficient photosensitizer under hypoxia conditions

Amphiphilic trismethylpyridylporphyrin-C70 (PC70) dyad with improved photosensitization has been successfully prepared. The PC70 dyad forms a liposomal nanostructure through molecular self-assembling. An increased absorption coefficient in the visible region, good biocompatibility, and high photostability were observed on the self-assembling structure. Surprisingly, in comparison with previously reported photosensitizer porphyrins, PC70 exhibited an enhanced photodynamic therapy (PDT) effect under hypoxia conditions. Further investigations illustrated that PC70 went through an extremely long-life triplet state (211.3 μs) under hypoxia, which enabled the exiguous oxygen to approach and interact with the activated (3P-C70)* more efficiently and produce more singlet oxygen. This would overcome the problem of existing photosensitizers of low PDT efficiency in cancerous tissues under hypoxia. The excellent properties of PC70 dyad make it a promising phototherapeutic agent, especially for the treatment of early- and late-stage cancers under shallow and hypoxia tissues.

Recent Progress of Molecular Imaging Probes Based on Gadofullerenes

Abstract Paramagnetic gadofullerenes and their derivatives exhibit more advantages than commercial Magnevist™ (Gd-DTPA) therefore have become competitive candidates for MR imaging probes. One of the most important properties is the stable fullerene cages are believed to hinder both chemical attacks on the inner clusters and the escape of the toxic lanthanide ions, which should effectively suppress the toxicity of naked Gd 3+ ions. Some functionalized gadofullerides are also available for further conjugation to fabricate multifunctional probes. This review presented the latest findings of MRI imaging probes based on various gadofullerenes, including Gd@C 60 , Gd@C 82 and Gd 3 N@C 80 and discussed the derivative strategy of gadofullerenes determining their relaxivity properties, biodistributions as well as their potential applications as nanoplatform for multifunctional probes.

Synergistic Effect of Human Serum Albumin and Fullerene on Gd-DO3A for Tumor-Targeting Imaging

A macromolecular magnetic resonance imaging (MRI) contrast agent was successfully synthesized by conjugating the gadolinium/1,4,7,10-tetraazacyclododecane-1,4,7-tetracetic acid complex (Gd-DO3A) with 6,6-phenyl-C61 butyric acid (PC61BA) and upon further modification with human serum albumin (HSA). The final product, PC61BA-(Gd-DO3A)/HSA, has a high stability and exhibits a much higher relaxivity (r1 = 89.1 mM(-1) s(-1) at 0.5 T, 300 K) than Gd-DO3A (r1 = 4.7 mM(-1) s(-1)) does under the same condition, producing the synergistic positive effect of HSA and C60 on the relaxivity of Gd-DO3A. The in vivo MR images of PC61BA-(Gd-DO3A)/HSA-treated tumor-bearing mice show strong signal enhancement for the tumor area due to the enhanced permeability and retention effect. The maximum accumulation of PC61BA-(Gd-DO3A)/HSA at the tumor site was achieved at 4 h postinjection, which may guide surgery. The results from the hematology and histological observations indicate that PC61BA-(Gd-DO3A)/HSA has no obvious toxicity in vivo. These unique properties of PC61BA-(Gd-DO3A)/HSA enable them to be highly efficient for tumor-targeting MRI in vivo, possibly providing a good solution for tumor diagnosis.

A Versatile and Clearable Nanocarbon Theranostic Based on Carbon Dots and Gadolinium Metallofullerene Nanocrystals

Nanocarbons such as carbon nanotubes, graphene derivatives, and carbon nanohorns have illustrated their potential uses as cancer theranostics owing to their intrinsic fluorescence or NIR absorbance as well as superior cargo loading capacity. However, some problems still need to be addressed, such as the fates and long-term toxicology of different nanocarbons in vivo and the improvement of their performance in various biomedical imaging-guided cancer therapy systems. Herein, a versatile and clearable nanocarbon theranostic based on carbon dots (CDs) and gadolinium metallofullerene nanocrystals (GFNCs) is first developed, in which GFNCs enhance the tumor accumulation of CDs, and CDs enhance the relaxivity of GFNCs, leading to an efficient multimodal imaging-guided photodynamic therapy in vivo without obvious long-term toxicity. Furthermore, biochemical analysis reveals that the novel nanotheranostic can harmlessly eliminate from the body in a reasonable period of time after exerting diagnostic and therapeutic function.

A novel bone marrow targeted gadofullerene agent protect against oxidative injury in chemotherapy

Chemotherapy as an effective cancer treatment technique has been widely used in tumor therapy. However, it is still a challenge to overcome the serious side effects of chemotherapy, especially for its myelotoxicity. Here we report a novel strategy using the water soluble gadofullerene nanocrystals (GFNCs) to protect against chemotherapy injury in hepatocarcinoma bearing mice, which was induced by the commonly chemotherapeutic agent cyclophosphamide (CTX). The GFNCs were revealed to specifically accumulate in the bone marrow after intravenously injecting to mice and they exhibited excellent radical scavenging function, resulting in a prominent increase of mice blood cells and pathological improvements of the primary organs in the GFNCs (15 mg kg−1) treated mice after the CTX (60 mg kg−1) therapy. Moreover, the GFNCs maintained and even strengthened the antineoplastic activity of the CTX agent. Therefore, the GFNCs would be the promising chemoprotective agents in chemotherapy based on their high efficiency, low toxicity and metabolizable property.摘要本文报道了一种利用金属富勒烯纳米材料实现肿瘤化疗骨髓保护的新技术. 肿瘤化疗往往会带来严重的骨髓抑制等毒副作用, 给患者 造成极大的创伤. 利用金属富勒烯纳米材料高效清除自由基、高选择性且快速富集在小鼠骨髓中的特性, 开发了基于金属富勒烯的新型化疗 辅助药物. 研究表明, 金属富勒烯实现了多方面的化疗保护效果, 对白细胞计数最高可提升166%, 对淋巴细胞最高可提升285%, 对于骨髓以及 脾脏多器官均有显著保护效果, 且未影响化疗药物的肿瘤治疗效果. 该材料是一种快速、高效、毒副作用小的新型肿瘤化疗辅助药物, 具有巨 大的发展潜力.

Amino acid functionalized gadofullerene nanoparticles with superior antitumor activity via destruction of tumor vasculature in vivo

Researchers have been puzzled of the therapy of malignant tumors and the current therapeutic strategies are always accompanied by toxicity or side effects. Developing efficient nanodrugs could reduce the dosage and greatly improve the therapeutic effects in cancer treatments. Here we initially reported a novel kind of gadofullerene nanoparticles functionalized with amino acid (β-alanine), which exhibited a superior antitumor activity in hepatoma H22 models via a novel therapeutic mechanism. The involvement of β-alanine improved the tumor inhibition rate up to 76.85% for a single treatment by strengthening the interaction with radiofrequency (RF) and extending blood circulation time. It realized a highly antivascular treatment to cut off the nutrient supply of tumor cells by physically destroying the abnormal tumor blood vessels assisted by RF. In situ and real-time observation of the vascular change was conducted using the dorsal skin fold chamber model, which corresponded to the erythrocyte diapedesis in histopathological examination. The ultrastructural changes of vascular endothelial cells were further investigated by environmental scanning electron microscopy and transmission electron microscopy. Long-term toxicity evaluation showed that the GF-Ala nanoparticles could be eliminated from the mice after several days and no obvious toxicity was found to the main organs. All these encouraging results suggest GF-Ala nanoparticles are valuable for the significant therapeutic potential with high-efficacy and low-toxicity.

The effect of hemiketals on the relaxivity of endohedral gadofullerenols

Gadofullerenols have received much attention due to their high relaxivities and low-toxicity as magnetic resonance imaging (MRI) contrast agents. However, the relaxivities of gadofullerenols vary in different reports. In this study, Gd@C-82(OH)(x)O-y with different hemiketal content were synthesized and the influence of this factor on water proton relaxation was investigated. The results show that Gd@C-82(OH)(x)O-y with more hemiketals exhibit much higher relaxivities than those with fewer hemiketals. The hemiketal structure is supposed to promote the formation of intermolecular hydrogen bonds, and finally lead to large aggregates. This is consistent with a previous report that the relaxivities of endohedral gadofullerene derivatives are strongly associated with the aggregate size. Hence, this work provides an important strategy for the manipulation of the relaxivities of gadofullerene based MRI contrast agents by controlling the quantity of hemiketals on the carbon cage.

Radioactive lutetium metallofullerene 177LuxLu(3−x)N@C80–PCBPEG derivative: a potential tumor-targeted theranostic agent

A radioactive metallofullerene 177LuxLu(3-x)N@C80 was firstly synthesized by means of neutron irradiation on Lu3N@C80. After modification by methoxypolyethylene glycol amine, in vivo investigation on tumor-bearing mice was performed. The results reveal favorable affinity toward tumors, suggesting that the obtained 177LuxLu(3-x)N@C80-PCBPEG could be promising for tumor diagnosis and therapy.