The Cytotoxicity And Targeted Drug Delivery Property Of Single Walled Carbon Nanotubes

Single walled carbon nanotubes (SWNTs) are emerging as one of the mostpromising drug carriers for cancer chemotherapy due to their possible advantagesover the clinically available spherical nanoparticles, including remarkable cellmembrane penetrability, high drug-carrying capacities, pH-dependent therapeuticunloading and easy modification. However, the toxicity data of SWNTs are ofteninconsistent and even conflicting for lacking of a standard test measure. Therefore, itis still necessary to establish a standard measure and systematically assess the toxicityof SWNTs for the biomedical applications. It is important to investigate therelationship between the toxicity of SWNTs and their surface properties, which has animportant guiding role for the SWNTs’ applications. In addition, preparation andevaluation of SWNTs based drug delivery systems is also a hotspot.The paper systematically assessed the toxicity of SWNTs by available commontest kits and tried to establish a toxicity test standard of SWNTs. We also prepared aseries of biomolecules functionalized SWNTs and investigate the relationshipbetween the toxicity of functionalized SWNTs and their surface properties. Based onthe above results, a brand new targeted anti-cancer drug delivery system involvedfolic acid (FA) terminated polyethylene glycol (PEG) wrapping on SWNTs wasdesigned and prepared. The details are as follows：(1) We investigated the cytotoxicity of raw SWNTs, purified SWNTs and cutSWNTs by some common test kits such as MTT, WST-1and CKK. It was found thatWST-1is an appropriate test method for detecting the cytotoxicity of SWNTs whileMTT assay gave incorrect results. Further more, Reactive oxygen species (ROS) andLactate dehydrogenase (LDH) assay revealed that purification and cut were necessaryproceed for SWNTs before they were used for drug delivery. (2) Biomolecules include amylose (AMY), alginate sodium (ALG), polyethyleneglycol (PEG) and chitosan (CHI) were employed for noncovalently wrapping aroundthe cut SWNTs to prepare four types of modified SWNTs. Only ether bond andhydroxyl group appeared on the molecular chains of AMY and PEG while CHI andALG have amino and carboxyl groups, respectively. The ether bonds and hydroxylgroups benefit the biocompatibility of SWNTs while amino and carboxyl groupstend to cause ROS and cytotoxicity. The positively charged CHI/SWNTs tend toabsorb on negatively charged cell membranes, leading to obviously cytotoxicity athigh concentration. Although ALG/SWNTs cause high ROS release in mitochondria,ALG/SWNTs showed lower toxicity because they are difficult to enter cells.(3) A brand new targeted anti-cancer drug delivery system involved folic acid(FA) terminated PEG wrapping on SWNTs and then loading anti-cancer doxorubicin(DOX). The new drug delivery system(DDS) are cheap and easy preparation as wellas high drug-carrying capacities, pH-dependent unloading and prolonged circulationtime. The drug system (DOX/PEG-FA/SWNTs) exhibit excellent stability underneutral pH conditions such as serum, but efficiently releases DOX at reduced pHtypical of the tumour environment and intracellular lysosomes and endosomes.DOX/PEG-FA/SWNTs is more selective and effective than the free drug andnon-targeting DOX/PEG/SWNTs to kill tumour cells. The low temperature andFR-blocked and endocytosis-inhibition results further suggest thatDOX/PEG-FA/SWNTs tend to attach onto HeLa cells by FA targeting and enter thelysosomes or endosomes by clathrin-mediated endocytosis. The DOX can be releasedand migrates into the nucleus to inhibit transcription and induce cell death.