Carbon nanotube lipid drug approach for targeted delivery of a chemotherapy drug in a human breast cancer xenograft animal model

• Published in: Biomaterials Vol. 34; no. 38; pp. 10109 - 10119
• Main Authors: Shao, Wei, Paul, Arghya, Zhao, Bin, Lee, Crystal, Rodes, Laetitia, Prakash, Satya
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.12.2013
• Subjects: Advanced Basic Science; animal models; Animals; Antineoplastic Agents, Phytogenic; blood; Breast cancer; breast neoplasms; Breast Neoplasms - drug therapy; carbon nanotubes; Cell Cycle - drug effects; Cell Line, Tumor; cytotoxicity; Dentistry; drug carriers; Drug Delivery Systems - methods; drug therapy; drugs; Fatty Alcohols - administration & dosage; Fatty Alcohols - therapeutic use; Female; folic acid; Humans; hydrophobic bonding; Mice; Mice, Inbred BALB C; Mice, Nude; Nanomedicine; Nanomedicine - methods; Nanotubes, Carbon - chemistry; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - therapeutic use; Single-walled carbon nanotubes; Targeted drug delivery; Xenograft Model Antitumor Assays; Targeted drug delivery; Breast cancer; Single-walled carbon nanotubes; Nanomedicine; Paclitaxel
• ISSN: 0142-9612; 1878-5905; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.09.007

Carbon nanotube (CNT) possesses excellent properties as a drug carrier. To overcome the challenge of drug functionalization with CNT, we have developed a lipid-drug approach for efficient drug loading onto CNT, in which a long chain lipid molecule is conjugated to the drug molecule so that the lipid-drug can be loaded directly onto CNT through binding of the lipid ‘tail’ in the drug molecule to CNT surfaces via hydrophobic interactions. In a proof-of-concept study, drug paclitaxel (PTX) was conjugated with a non-toxic lipid molecule docosanol for functionalization with CNT. Folic acid was also conjugated to CNT for targeted drug delivery. High level of drug loading onto SWNT could be achieved by lipid-drug approach. Conjugation of FA to SWNT-lipid-PTX led to an increase in cell penetration capacity, and the targeted SWNT-lipid-PTX showed much improved drug efficacy in vitro in comparison to free drug Taxol and non-targeted SWNT-lipid-PTX at 48 h (78.5% vs. 31.6% and 59.1% in cytotoxicity respectively, p < 0.01). In vivo analysis using a human breast cancer xenograft mice model also confirmed the improved drug efficacy. The targeted SWNT-lipid-PTX was found non-toxic as evaluated by biochemical analysis using blood samples, and by histological analysis of major organs.