| Telomerase activity has been found in ~85-90% of all human tumors but not in adjacent normal cells. This makes telomerase a target not only for cancer diagnosis but also for the development of novel gene therapeutic agents. Antisense oligodeoxynucleotides (ASODNs) designed to hybridize with target mRNA sequences down regulate the expression of the corresponding translated proteins. Although ASODNs have emerged as an exciting and promising strategy in the field of cancer therapy in recent years, their development in viable therapeutic systems has faced challenges due to their susceptibility to enzyme degradation and poor intracellular uptake. Therefore, suitable drug delivery systems are needed to develop for effectively improving cellular uptake and stability of ASODNs.Carbon nanotubes (CNTs), with unique structural, electronic and mechanical properties, have been rapidly exploring in the biological and medical applications, especially the use of functionalization CNTs as carriers of fluorescent dyes, bioactive molecules and drugs. In the life science, fluorescence imaging is an important technology. However, the mostly used organic fluorescent dyes suffer from several limitations including photobleaching, narrow excitation spectra, broad emission spectra, etc. Semiconductor quantum dots (QDs) offer advantages over conventional organic dye molecules. These unique optical properties of semiconductor quantum dots (QDs) make them appealing as fluoresecent probes for biological labeling and long-term tracking of biological processes.This paper is focused on the research of functionalized multiwalled carbon nanotubes and its nanobiotechnology applications.1. Preparation of functionalized multiwalled carbon nanotubes and evaluation of its biocompatibilityThe combined treatment of strong acids and sonication is known to reduce the CNTs length and generate anionic groups (mainly carboxylate) along the sidewalls and ends of the nanotubes. Four types of cationic polyelectrolytes, Polyethylenimine (PEI), Poly(diallyldimethylammonium) chloride (PDDA), Poly(amidoamine) (PAMAM) dendrimers and Chitosan were used to modify oxidized MWNTs to obtain functionalized MWNTs (f-MWNTs), respectively. The biological properties of oxidized MWNTs and f-MWNTs were analyzed by flow cytometry, the cationic polymers modified MWNTs clearly reduced the toxic effects compared with the oxidized MWNTs. Especially, nearly all the cells were observed to survive upon treatment with PEI functionalized MWNTs, showing a minimum level of cell death similar to the untreated cells. These results indicate that PEI-MWNTs exhibit little toxicity to HeLa cells. 2. Multiwalled carbon nanotubes decorated with multi-color quantum dots for intracellular fluorescent labelingWe present a novel multi-color fluorescent intracellular nanoprobe prepared by electrostatically assembling differently sized CdTe quantum dots to polyethylenimine (PEI) functionalized multiwalled carbon nanotubes (MWNTs). The MWNTs-PEI-CdTe nanoassemblies exhibited high water-solubility, intensive visible light emisions, efficient intracellular transporting, strong intracellular tracking and high delivery efficiency.3. Intracellular delivery of quantum dots tagged antisense oligodeoxynucleotides by functionalized multiwalled carbon nanotubesWe have prepared a novel double functionalization of carbon nanotube delivery scheme containing therapeutic gene and QDs labeling, CdTe tagged ASODNs-PEI-MWNTs, via electrostatically layer-by-layer assembling. With this novel functionalization, we have demonstrated efficient intracellular transporting, strong cell nucleus localization and high delivery efficiency of ASODNs by the PEI-MWNTs carriers. Furthermore, the ASODNs bound to PEI-MWNTs show their effective anticancer activity. Therefore, these functionalized MWNTs could hold great promising for biological delivery applications and gene therapy. |
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