Hyaluronate Functionalized Multi-Wall Carbon Nanotubes Filled with Carboplatin as a Novel Drug Nanocarrier against Murine Lung Cancer Cells

Abstract

Carbon nanotubes (CNTs) have emerged in recent years as a potential option for drug delivery, due to their high functionalization capacity. Biocompatibility and selectivity using tissue-specific biomolecules can optimize the specificity, pharmacokinetics and stability of the drug. In this study, we design, develop and characterize a drug nanovector (oxCNTs-HA-CPT) conjugating oxidated multi-wall carbon nanotubes (oxCNTs) with hyaluronate (HA) and carboplatin (CPT) as a treatment in a lung cancer model in vitro. Subsequently, we exposed TC–1 and NIH/3T3 cell lines to the nanovectors and measured cell uptake, cell viability, and oxidative stress induction. The characterization of oxCNTs-HA-CPT reveals that on their surface, they have HA. On the other hand, oxCNTs-HA-CPT were endocytosed in greater proportion by tumor cells than by fibroblasts, and likewise, the cytotoxic effect was significantly higher in tumor cells. These results show the therapeutic potential that nanovectors possess; however, future studies should be carried out to determine the death pathways involved, as well as their effect on in vivo models.

Hyaluronate Functionalized Multi-Wall Carbon Nanotubes Loaded with Carboplatin Enhance Cytotoxicity on Human Cancer Cell Lines

“…Our previous study [29] showed that oxCNTs-HA-CPT have an excellent and specific antitumor effect in vitro, and the cytotoxic effect of the as-prepared nanovectors was demonstrated significantly higher in murine tumor cells TC-1 [29]. The application of such nanovector in an in vivo tumor model serves to know its effects in a broader sense.…”

“…Considering that drug delivery to cells is safer and more effective than conventional therapies [35], several studies have shown that CNTs are excellent carriers because CNTs can penetrate directly into cells and deliver the drug intact and unmetabolized during transport [36]. In the present study, a nanovector prepared from MWCNTs (outside diameter, 30-80 nm) was oxidized and functionalized with HA and filled with CPT, following a previous methodology [29].…”

“…The commercial-grade carbon nanotubes (cCNTs) were purchased from Nanostructured & Amorphous Materials, Inc. (NanoAmor ® , Houston, TX, USA, Stock # 1245YJF, CAS # 99685-96-8). For the synthesis and characterization of the nanovector, the previously described methodology was used [29]. Briefly, oxidation of the cCNTs was performed using 50 mg of cCNTs, which were reacted with H 2 SO 4 and HNO 3 (3:1) in an ultrasound bath for 1 h and subsequently under magnetic stirring for 24 h. Oxidized CNTs (oxCNTs) were obtained, which were washed with distilled water until their pH was neutralized.…”

“…Micrographs of the nanotubes were obtained at 20,000×. Chemical characterization of the as-prepared nanovectors was recently reported in another study [29].…”

“…CPT-loaded PEGylated-modified MWCNTs, however, turned out to be ineffective on the viability of MDA-MB-231 (human breast cancer) cells [28]. Previously, in our research team, we described a new antineoplastic therapeutic strategy using a nanovector fabricated with MWCNTs and functionalized with HA to be loaded with CPT [29]. Such MWCNTs-HA-CPT nanovector showed selective cytotoxic activity against TC-1 murine lung cancer tumor cells.…”