The Study Of Biocompatibility Of Pristine And Functionalized Multi-walled Carbon Nanotubes

Chemotherapy is one of the main means to treat malignant tumors. Though diverse chemotherapeutics have already been developed and applied in clinical practice, no evident improvements in long-term survival rate of patients with malignant tumors have been achieved. The major reason for this failure lies in lack of selectivity of killing effects for malignant cells of these traditional chemotherapeutic drugs used in clinical practice at present. The in vivo distribution of these drugs lacks targeting. Besides aggregating in local lesions of carcinoma, these drugs gather in normal tissues and organs as well. Therefore, they inflict casualties on non-diseased tissues and cells while killing malignant cells, leading to toxic side reactions, low curative effects, and bad tolerance for patients. As further research of tumor pathogenesis advances, treatments for tumors progress in the direction of comprehensiveness, targeting and individuality treatment modalities. It has become urgent to enhance the anti-carcinoma effects and at the same time lower the unwanted side effects of chemotherapeutics for clinical practice of malignant tumors for the time being. The rise and development of nanotechnologies and their applications in medicine, pharmacy and oncology provide promising means and methods for targeting chemotherapy of tumors.The nanobiotechnology coming from integration of nanotechnology into biological technology is standing in the forefront of biological technological fields of international academic communities and has been given the priority of research and development. Moreover, the fruitful results from these studies have been used in medical and pharmaceutical fields. Among these biological branches, applications of nanotechnology in oncology are attracting more and more attention. Nowadays, development of drug delivery systems (DDS) of nanoparticles conjugated drugs based upon nanoscale medicine preparations is one of the important developmental orientations of pharmacology. Drug delivery systems can be loaded with drugs and developers, convey and target them to tumors. At present, numerous domestic and international investigation institutes are dedicating themselves to research and development of novel complex anticancer drugs which are loaded with chemotherapeutics and targeting molecules covalently linked to nanomaterials. These complex anticancer drugs of nanoscales possess excellent properties that are shared exclusively by all nanoscale materials such as ultrasmall diameter, the maximum aspect ratio and specific surface areas, mentioning only a little among them. These special characteristics render these novel complex anticancer drugs highly selective, efficient, less toxic and release controllable. These outstanding features and performances of new compound anticancer drugs surpass their traditional counterparts, greatly enhancing safety and efficiency of these chemotherapeutics. For this reason, the newly developed anticancer drugs are promising treatments in terms of improving survival rates and life qualities of malignancy sufferers, and in the end, open up new prospects for human beings to achieve the ultimate goal of conquering malignant diseases at last.Among the various nanomaterials used in drug delivery systems, carbon nanotubes (CNTs) are one of the most deeply studied. Prior to application of novel complex anti-cancer drugs based on nanotechnologies in clinical practice, the study of toxicity profiles of these carbon materials of nanometer scale has always been hot topics of biological world. There are many disparities in conclusions on toxicity of carbon nanotubes from different laboratories. The main reason for the divergence lies in that different researchers used different carbon nanotubes and method of administration.Here in the current research, we curtained long MWCNTs to short tubes with particular length, designated as MWCNTs, synthesized and functionalized short MWCNTs (about200nm) with branched, biocompatible polyethylene glycol (PEG), designated as PEG-MWCNTs, to render high aqueous solubility and stability in physiological solutions including serum. The synthesized carbon nanotubes are then cocultured with cells to observe their effects on cell growth. They are also injected into circulation of animals via tail vein to evaluate the morphological and functional changes through preparation of histological tissue sections and measurement of biological indices of major organs. The results indicate that pristine (MWCNTs) and PEG-functionalized multi-walled carbon nanotubes (PEG-MWCNTs) through intravenous administration respectively produce a different spectrum of toxicities from that reported following intratracheal instillation exposures.This study includes three parts:1. Synthesis of short MWCNTs and polymer functionalized MWCNTs via physic and chemical processes. Detection and characterization indicate that these synthesized CNTs are curtailed (about200nm) in length. PEG-MWCNTs are soluble and stable in various solutions including normal saline (NS), phosphorate buffer solution(PBS), deoinized water (ddH2O), cell culture medium (DMEM) with or without10%bovine serum albumin(BSA). MWCNTs are soluble in the solutions above except cell culture medium without10%bovine serum albumin.2. In vitro effects of pristine and functionalized multi-walled carbon nanotubes. Trypan blue exclusion assay indicates these two types of carbon nanotubes themselves exert no killing effects on SKBR-3cells. ELISA assays reveal no pro-inflammatory effects of either type of carbon nanotubes on mouse pulmonary microvascular endothelial cells and mouse brain microvascular endothelial cells.3. In vivo effects of pristine and functionalized multi-walled carbon nanotubes. Carbon nanotubes are injected into mice circulation through tail vein. Results demonstrate that neither pristine nor polymer functionalized short multi-walled carbon nanotubes has harmful influences on animal hemogram, coagulation function, heart, liver and kidney functions and they are not pro-inflammatory. Paraffin sections show no morphological changes of heart, liver and kidney or no deposition of black carbon nanotubes in these major organs.In conclusion, current results confirm our predication that curtailed and polyethylene glycol (PEG) modified multi-walled carbon nanotubes both possess plausible biocompatibility, paving the way for synthesizing novel nanocomposites of anti-cancer drugs which utilize these nontoxic carbon nanotubes as potential vehicles and special molecules as targeting moieties for targeting strategy of malignant tumor chemotherapy.