Covalently Combining Carbon Nanotubes with Anticancer Agent: Preparation and Antitumor Activity

Abstract

A multiwalled carbon nanotube (MWNT)-based drug delivery system was developed by covalently combining carbon nanotubes with the antitumor agent 10-hydroxycamptothecin (HCPT) using hydrophilic diaminotriethylene glycol as the spacer between nanotube and drug moieties. The surface functionalizations of the nanotube were carried out by enrichment of carboxylic groups with optimized oxidization treatment, followed by covalently linking hydrophilic diaminotriethylene glycol via amidation reaction, and then HCPT was chemically attached to carbon nanotubes through a cleavable ester linkage. It is demonstrated that the obtained MWNT-HCPT conjugates are superior in antitumor activity both in vitro and in vivo to clinical HCPT formulation. In vivo single photon emission computed tomography (SPECT) imaging and ex vivo gamma scintillation counting analyses reveal that MWNT-HCPT conjugates have relatively long blood circulation and high drug accumulation in the tumor site. These properties together with the enhanced cell uptake and multivalent presentation of HCPT on a single nanotube benefit substantially the antitumor effects and would boost significantly the applications of carbon nanotubes in the biomedicine field.

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

“…Although carbon nanotubes are completely insoluble in all solvents, creating toxicity problems, limiting their length and diameter diminish this toxicity, and chemical modifications to their structure transform them in water-soluble carriers, increasing their biocompatibility and decreasing their toxicity [292][293][294]. Different anticancer drugs can be included in their inner cavity [295,296] or in their surface [297] with a high payload due to their ultrahigh surface area. These novel carriers have the ability of cross the plasma membrane and enter into the cancerous cells (by endocytosis or penetration like a needle), having no influence the type of functionalization of the nanotubes or the type of cancer cells [298,299].…”

“…There are no FDA approvals or clinical trials in process up to date using carbon nanotubes, although the encouraging preclinical results in vitro and in vivo in cancer treatment via passive targeting show that this structures are promising nanocarriers for cancer treatment [18,126,296,297,300,[307][308][309][310][311][312][313][314][315][316]. Active tumor targeting has been rarely reported in vivo [300,317,318], usually without drug loading [301,303,319].…”

Carbon Nanotubes: a viable drug delivery platform for the treatment of cancer

“…Drug vectorization by covalent bond is achieved using spacer agents as ethylenediamine, cisteamine, diaminotriethylene glycol, etc to link the drug directly to the NTC (Wu et al, 2009, Bhirde et al, 2009, Samori 2010, or the drug can be link to functionalizing agent by esterification (Chen et al, 2012, Marega et al, 2011.…”

Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells

“…16 Since the noncovalent interaction is not as robust as covalent linkage, the early release of the drug before reaching the pharmacologic tissues should be inevitable. Small drug molecules have been covalently conjugated to f-CNTs through amide bonds, 12 disulfide bonds, 17 ester bonds, 18,19 and carbamate bonds 20 for in-vitro and in-vivo delivery. To improve the cellular uptake of tumor cells, drug molecules were linked to the same nanotubes together with tumor-targeting molecules that could specifically recognize cancer-specific receptors on the cell surface and induce receptor-mediated endocytosis.…”