The application of carbon nanotubes in target drug delivery systems for cancer therapies

Abstract

Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.

Figure 1

The formation of SWCNT and its physical and chemical treatment for use as drug carriers. (A) The schematic illustration of the structure formation of SWCNTs with the two ends closed. (B) The schematic illustration of the strategy for the preparation of the CNT-based drug delivery systems.

Figure 2

The modification of CNTs. Schematic illustration of modification of CNTs with various molecules. 1, Dhar et al. [70]; 2, Jia et al. [13]; 3, Georgakilas et al. 2002 [16]; 4, Peng et al. 1998; 5, Liu et al. [91]; 6, Gu et al. 2008; 7, Son et al. 2008; 8, Klingeler et al. 2009.

Figure 3

The absorption of SWCNTs through intestinal columnar epithelial cells [10]. (A) SWCNTs (arrows) found in the intestinal mucous membrane. (B) Magnification of the cell indicated by the left arrow in (A). Ve, transportion vehicles; Vi, villus of the columnar cells. (C) Magnification of the Ve, which has membrane with double lipid layers (arrow).

Figure 4

SWCNTs enter the neurons in brain through axoplasmic transportation [10]. (A) SWCNTs in the lysosomes of a neuron (arrows); (B) the magnification of the two lysosomes containing SWCNTs; (C) there are no SWCNTs in glial cells; (D) a bundle of SWCNTs parallel to the neurite in the section along the longitudinal axis of the neurite; (E) the SWCNTs are dot-like in the section vertical to the longitudinal axis of the neurite.

Figure 5

The schematic illustration of the mechanisms of SWCNT to induce cell damage. Based on the studies of Yang et al. [10]. SWCNTs interact with the mitochondria electron transmission chains (ETC) (by binding to ETC?) after they enter into mitochondria (1); The interaction of SWCNTs with ETC blocks the transmission of electrons, which results in the increase of the leaking of free electrons from ETC (2); The leaked free electrons form free radicals H₂O₂ or reactive oxygen species (ROS) (3); The free radicals or ROS attack the membrane system of mitochondria through peroxidation (4); Then the free radicals or ROS diffuse through the damaged mitochondrial membrane to lysosomes to destroy the membrane of the lysosomes (5); The injured lysosomes release digestive enzymes, leading to the damage or death of the whole cells. On the other hand, the blocking of ETC makes mitochondria incapable of producing ATP (7), which results in the depletion of energy for the living activities of the cells, also leading to the damage or death of the whole cells (8).

Figure 6

The schematic illustration of the strategies. For the studies on the best use of CNTs as drug carriers. The best treatment effects are in the center of the strategies that are the ultimate purpose of our studies, which can be achieved by the studies of three effects: the weighing between treatment effects and the side or toxic effects, the pharmacological mechanism that makes it possible to use the advantages to outmost and the toxicological mechanism that makes people capable of decreasing or avoiding the side or toxic effects.