First Soluble M@C60 Derivatives Provide Enhanced Access to Metallofullerenes and Permit in Vivo Evaluation of Gd@C60[C(COOH)2]10 as a MRI Contrast Agent

Bolskar, Robert D.; Benedetto, Angelo F.; Husebo, Lars O.; Price, Roger E.; Jackson, Edward F.; Wallace, Sidney; Wilson, Lon J.; Alford, J. M.

doi:10.1021/ja0340984

Cited by 405 publications

(342 citation statements)

References 56 publications

Supporting

Mentioning

333

Contrasting

Unclassified

Order By: Relevance

“…Metallofullerenes with gadolinium (Gd) have been demonstrated to be capable of effectively enhancing magnetic resonance image contrast (23). [Gd@C 82 (OH) 22 ] n , synthesized by our group, has been verified as a new generation of highly efficient contrast agents for magnetic resonance imaging (MRI) (24)(25)(26)(27). It is a hydroxylated fullerene forming a cage encapsulating gadolinium inside (Fig.…”

Section: Resultsmentioning

confidence: 99%

Metallofullerene nanoparticles circumvent tumor resistance to cisplatin by reactivating endocytosis

Lü

Meng

Wang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

235

160

View full text Add to dashboard Cite

Cisplatin is a chemotherapeutic drug commonly used in clinics. However, acquired resistance confines its application in chemotherapeutics. To overcome the acquired resistance to cisplatin, it is reasoned, based on our previous findings of mediation of cellular responses by [Gd@C 82 (OH) 22 ] n nanoparticles, that [Gd@C 82 (OH) 22 ] n may reverse tumor resistance to cisplatin by reactivating the impaired endocytosis of cisplatin-resistant human prostate cancer (CP-r) cells. Here we report that exposure of the CP-r PC-3-luc cells to cisplatin in the presence of nontoxic [Gd@C 82 (OH) 22 ] n not only decreased the number of surviving CP-r cells but also inhibited growth of the CP-r tumors in athymic nude mice as measured by both optical and MRI. Labeling the CP-r PC-3 cells with transferrin, an endocytotic marker, demonstrated that pretreatment of the CPr PC-3-luc cells with [Gd@C 82 (OH) 22 ] n enhanced intracellular accumulation of cisplatin and formation of cisplatin-DNA adducts by restoring the defective endocytosis of the CP-r cancer cells. The results suggest that [Gd@C 82 (OH) 22 ] n nanoparticles overcome tumor resistance to cisplatin by increasing its intracellular accumulation through the mechanism of restoring defective endocytosis. The technology can be extended to other challenges related to multidrug resistance often found in cancer treatments.A s a major chemotherapeutic agent for tumor treatment, cisplatin remains a cornerstone of the present-day chemotherapy regimens against not only epithelial malignancies but also a number of metastatic and advanced malignancies (1, 2). However, because of high toxicity and easy development of drug resistance, successful treatment with cisplatin often is limited (3,4). Following the discovery of ATP-binding cassette (ABC) transporters and their roles in drug resistance in various types of tumors (5), much research has been done to explore the relationship between ABC transporter activity and specific chemotherapeutics, including cisplatin. Because no ABC transporter has been identified for "pumping" cisplatin out of cisplatin-resistant human prostate cancer (CP-r) cells (6-8), it would be difficult to sensitize CP-r cells by using any known strategy that targets resistant cancer cells by inhibiting multidrug resistance (MDR)-associated proteins on plasma membrane of the CP-r cells. Diffusion has been considered as a pathway for cisplatin to penetrate plasma membrane. Recently, studies have indicated that cisplatin entered cells by endocytosis and other mechanisms (9-12).To increase susceptibility of cancer cells to cisplatin, i.e., to reverse drug resistance, many efforts have been made through chemical modification, gene therapy, vector delivery, and other means (2, 9, 13). Combination of traditional chemotherapy with nanotechnology may provide a promising alternative for novel cancer treatments. The use of nanoparticles to sensitize tumor cells to cisplatin in vitro and in vivo has been described recently (14-16). In these studies, cisplatin-encap...

show abstract

Section: Resultsmentioning

confidence: 99%

Metallofullerene nanoparticles circumvent tumor resistance to cisplatin by reactivating endocytosis

Lü

Meng

Wang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

235

160

View full text Add to dashboard Cite

show abstract

“…46 Prato reactions have been carried out on La@C 82 to yield mono-and bis-adducts, with electron paramagnetic resonance measurements showing slight modification of the electronic structure upon monoaddition, and significant modification upon bisaddition. 56 Bingel cyclopropanation was used by Bolskar et al 57 to isolate a derivative of the otherwise insoluble Gd@C 60 . This is of value as the Gd@C 60 fraction of the arc discharge soot is more abundant than Gd@C 82 but could never be isolated due to its insolubility.…”

Section: Endohedral Metallofullerenesmentioning

confidence: 99%

Water-soluble fullerenes for medical applications

Rašović

2017

Materials Science and Technology

119

View full text Add to dashboard Cite

Research on fullerenes occupies a unique position in the scientific arena. Synthesis and characterisation of this nanomaterial blur the line between materials science and chemistry; careful tuning of the processing methods gives birth to a whole family of molecules and their functionalised derivatives, whose unusual properties at this nanoscopic scale can be exploited in cutting-edge technological applications. This review focuses on the functionalisation of fullerenes for use in medical applications. The first half gives an introduction to the fullerenes themselves and how their fundamental properties lead to a very rich chemistry, enabling both exohedral (external) and endohedral (internal) functionalisations of the cage. Emphasis is placed on the need for safe and reproducible synthesis routes if fullerenes are ever going to make it to the pharmaceutical market. In line with this, a selection of exohedral functionalisation protocols receives particular attention. Coverage of endohedral fullerene synthesis routes is limited to the endohedral metallofullerenes. In the second half, myriad applications of fullerenes in biomedical contexts are introduced and certain synthesis routes are critically evaluated. Discussion of the need to water solubilise the hydrophobic fullerene cages precedes an overview of fullerene-based diagnostic and therapeutic technologies. A final moment is spent on toxicity studies of fullerenes. The concluding remarks emphasise the positive effects of incorporating fullerenes into biomedical technologies, while looking at how these are perceived by the general public. A case is made for fullerenes being the optimal choice as standard bearers in the advance of nanomaterials into the medical field. This is the winning review of the 2016 Materials Literature Review Prize of the Institute of Materials, Minerals and Mining, run by the Editorial Board of MST. Sponsorship of the prize by TWI Ltd is gratefully acknowledged.

show abstract

“…[57][58][59][60][61] A holmium-encapsulated water-soluble metallofullerene derivative was adopted as a tracer to investigate its in vivo biological behaviors and distribution. Studies using Gd@C 82 (OH) x mainly focused on application as a new generation of MRI contrast agents that were both highly efficient and low in toxicity.…”

Section: Ros-scavenging Property Of Fullerenesmentioning

confidence: 99%

Therapeutic applications of low-toxicity spherical nanocarbon materials

Wang

et al. 2014

NPG Asia Mater

View full text Add to dashboard Cite

Nanocarbon materials have received considerable attention due to their unique structure and properties, which make them promising candidate materials for use in biomedical applications. In this review, we discuss the therapeutic applications of spherical nanocarbon materials, including fullerene nanoparticles, carbon nanohorn aggregates, nanodiamonds and porous carbon nanospheres, and their toxicology in biological systems. We put special emphasis on the antitumor effects of these multifunctional nanoparticles, which operate via novel mechanisms in a highly efficient manner. The low toxicities of these spherical nanocarbon materials as well as the possible effects of shape on toxicity are discussed.

show abstract

First Soluble M@C₆₀ Derivatives Provide Enhanced Access to Metallofullerenes and Permit in Vivo Evaluation of Gd@C₆₀[C(COOH)₂]₁₀ as a MRI Contrast Agent

Cited by 405 publications

References 56 publications

Metallofullerene nanoparticles circumvent tumor resistance to cisplatin by reactivating endocytosis

Metallofullerene nanoparticles circumvent tumor resistance to cisplatin by reactivating endocytosis

Water-soluble fullerenes for medical applications

Therapeutic applications of low-toxicity spherical nanocarbon materials

Contact Info

Product

Resources

About