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It is well known that shell-structured materials can be used for delivering drugs directly into objective-cells of the human body organs.

In these systems, the clinically active molecule is placed inside the shell, that are mainly constituted by organic materials such as polymeric shells, liposomes, microspheres or micelles, and a molecule capable to couple with surface molecules of the target cell is placed on the shell surface. A really efficient drug delivery system can count on very few combinations of active molecules, shell materials and targeting molecules able to ensure targeting efficiency, chemical stability and clinical effect. If single-wall carbon nanohorns (SWNHs) are used as shell material, because of their chemical and mechanical stability, the huge surface areas, the great number of horn interstices, an active molecules can be easily inserted their inner hollows, and their walls can be modified to achieve the desired targeting effect. In such manner, a drug delivery system can be precisely “tailored” and “programmed” to hit particular cells into the objective organ.

cisplatin

(a) and (b) HRTEM images of SWNH (scale bars of 10 and 2 nm, respectively). (a) and (b) HRTEM images of SWNH (scale bars of 10 and 2 nm, respectively). (c) Z-Contrast image of SWNH aggregate (10 nm). (d, e) HRTEM images of SWNH (10 and 2 nm) in which black spots are cisplatin clusters. (f) Z-Contrast image of SWNH in which bright spots are cisplatin clusters (10 nm). From: “Carbon Nanohorns as Anticancer Drug Carriers” - Mol. Pharm. , 2005, 2 (6), pp 475–480

    

Moreover, SWNHs with their stable spherical aggregate of 80−100 nm diameter, matches the ideal conditions for enhanced permeability and retention (EPR) effect: for example, SWCNH can permeate the tumor tissues by vessel circulation and stop there in consequence of poor lymphatic drainage.

The tiny diameters of SWNHs (2−5 nm) are ideal for the incorporation and the slow release of biologically active materials, that is a key requirement in drug delivery to reduce the losses  before the reaching of the target. In addition, extended studies in-vivo and in-vitro demonstrated as SWNHs alone do not exhibit cytotoxicity, making them potentially applicable to drug delivery systems.

Recent experiments  and patent show that anticancer agent, like cisplatin or others, can be incorporated into and released from SWNHs. The release rate was low, and the released active drug maintained its anti-cancer effects in vitro.

A recent study showed that kinds of carbon nanomaterials such as carbon nanotubes were useful for bone formation. In particular, the effect of SWCNHs on bone regeneration and their possible application for guided bone regeneration was evaluated. In this study cranial defects were created in rats and covered by a membrane with SWCNHs. At two weeks, bone formation under the membrane with CNHs shown great progresses, suggesting that macrophages induced by CNHs play a key role in this kind of bone regeneration.

Other possibilities in medical applications of SWCNH are demonstrated by authors that use the nanohorns to drive a thermo-activable molecule into tumoral cells or viruses, and acts as a destroyer when irradiated by light. Gadolinium oxides are used to decorate the SWCNH that, when perfused in living tissues, can reveal their distribution by means of Nuclear Magnetic Resonance Imaging (NMRI).

 

The high surface areas of carbon nanohorns allow the incorporation of molecular entities, such as polyamidoamine dendrimers. New hybrid systems of carbon nanohorns that hold polyamidoamine dendrimers are recently reported and one of these derivatives has been employed as an agent for gene delivery. The system is able to release interfering genetic material diminishing the levels of a house-keeping protein and a protein directly involved in prostate cancer development. Importantly, this hybrid material is also far less toxic than the corresponding free dendrimer. These results tend to conclude that these nanomaterials can be exploited as useful non-viral agents for gene therapy.

References & Examples

Assembly of single-walled carbon nanohorn supported liposome particles - (2011) Bioconjugate Chemistry, 22 (6), pp. 1012-1016.

Carbon nanohorns accelerate bone regeneration in rat calvarial bone defect - (2011) 2011 Nanotechnology 22 065102

Single-walled carbon nanohorns and their applications - (2010) Nanoscale, 2 (12), pp. 2538-2549.

Biodistribution and ultrastructural localization of single-walled carbon nanohorns determined in vivo with embedded Gd2O3 labels - (2009) ACS Nano, 3 (6), pp. 1399-1406.

Enhancement of in vivo anticancer effects of cisplatin by incorporation inside single-wall carbon nanohorns - (2008) ACS Nano, 2 (10), pp. 2057-2064.

Fabrication of ZnPc/protein nanohorns for double photodynamic and hyperthermic cancer phototherapy - (2008) Proceedings of the National Academy of Sciences of the United States of America, 105 (39), pp. 14773-14778.

Opportunities and challenges of carbon-based nanomaterials for cancer therapy - (2008) Expert Opinion on Drug Delivery, 5 (3), pp. 331-342.

Photoinduced antiviral carbon nanohorns - (2008) Nanotechnology, 19 (7), art. no. 075106.

Recent advances in inorganic nanoparticle-based drug delivery systems - (2008) Mini-Reviews in Medicinal Chemistry, 8 (2), pp. 175-183.

Dispersion of cisplatin-loaded carbon nanohorns with a conjugate comprised of an artificial peptide aptamer and polyethylene glycol - (2007) Molecular Pharmaceutics, 4 (5), pp. 723-729

Functionalization of carbon nanomaterials by evolutionary molecular engineering: Potential application in drug delivery systems - (2006) Journal of Drug Targeting, 14 (7), pp. 512-518.

Solubilization of single-wall carbon nanohorns using a PEG-doxorubicin conjugate - (2006) Molecular Pharmaceutics, 3 (4), pp. 407-414.

Preparing a magnetically responsive single-wall carbon nanohorn colloid by anchoring magnetite nanoparticles - (2006) Journal of Physical Chemistry B, 110 (14), pp. 7165-7170.

Carbon nanohorns as a novel drug carrier - (2006) Nippon rinsho. Japanese journal of clinical medicine., 64 (2), pp. 239-246.

Carbon nanohorns as anticancer drug carriers - (2005) Molecular Pharmaceutics, 2 (6), pp. 475-480.

Patent US2006193919 -  Complex of drug-carbon nanohorn and a process for producing the complex

Patent WO2011154894  -  Solutions of carbon nanohorns, method for making same and uses thereof

Carbon nanohorns functionalized with polyamidoamine dendrimers as efficient biocarrier materials for gene therapy - (2012) Carbon - in press

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