Carbon nanotubes as delivery systems for chemotherapeutics in 2D and 3D cell models

Download Statistics

Downloads

Downloads per month over past year

Ledezma Gallegos, Fabricio Noel (2021). Carbon nanotubes as delivery systems for chemotherapeutics in 2D and 3D cell models. University of Birmingham. Ph.D.

Preview

LedezmaGallegos2021PhD.pdf
Text - Accepted Version
Available under License All rights reserved.
Download (16MB) | Preview

Abstract

Despite significant advances in recent years, cancer remains a major worldwide health problem. Traditional chemotherapeutics are very potent, yet their administration is accompanied by severe adverse effects due to low specificity, as well as the development of resistance. Therefore, in efforts to improve the success of current therapies, nanomedicine has presented revolutionary approaches in the delivery of anticancer drugs. In this context, carbon nanotubes have emerged as a promising drug delivery system due to their unique structure and physicochemical properties, offering a wide variety of opportunities for biomedical applications. This thesis presents the development of novel anticancer therapeutic modalities through the integration of multi-walled carbon nanotubes (MWNTs) with the first-line antineoplastic agents cisplatin (CDDP) or doxorubicin (DOX).

Thorough physicochemical characterisation of Pluronic-coated MWNTs, carboxyl- MWNTs and amine-MWNTs was performed to measure relevant aspects such as MWNT length, surface functionalisation and charge, concluding that the chemically functionalised MWNT were highly-dispersible and biocompatible. Furthermore, the anticancer activity of MWNTs + DOX and MWNTs + CDDP complexes was assessed on breast carcinoma (MCF7) 2D cells and 3D tumour spheroids, generated with a low-cost and reliable method. While the combination of MWNTs + DOX depicted a comparable efficacy of that observed with free DOX, MWNTs + CDDP complexes displayed a marked enhanced therapeutic efficacy compared to CDDP alone, resulting in higher cytotoxicity in monolayer 2D cultures as well as greater growth inhibition and even disaggregation of the 3D spheroids. Further analysis revealed that carboxylated MWNTs + CDDP complexes increased the intracellular accumulation of CDDP, leading to oxidative imbalance, cell cycle arrest and apoptosis induction. This work highlights the development of a promising therapeutic modality for the treatment of breast cancer that demonstrated to not only efficiently chemo-sensitise cancer cells to CDDP, but also enhance the anti-tumour efficacy in 2D and 3D cellular models.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):