Very happy to share our recent study in collaboration with researchers from the Indira Gandhi National Tribal University, Lalpur, Amarkantak, Madhya Pradesh, India. The paper explores the development of functionalized carbon nanotubes in cancer treatment. The primary objective was to create a targeted drug delivery system for doxorubicin (Dox), a widely used anti-cancer drug, specifically aimed at breast cancer cells. A combination of computational modeling and experimental validation was used to achieve this goal. Molecular dynamics simulations were utilized to predict the interactions between the drug and the functionalized multi-walled carbon nanotubes (MWCNTs), estimate the drug loading capacity, and study the pH-dependent release mechanisms. These predictions were then validated through various in vitro experiments, including drug loading capacity tests, pH-sensitive release studies, cytotoxicity assays, and cellular uptake studies.
The key findings of the study highlighted the enhanced drug loading capacity of the functionalized MWCNTs compared to their pristine counterparts, attributed to improved interactions such as π-π stacking and hydrogen bonding. The nanocarriers also demonstrated controlled release of doxorubicin at the acidic pH typical of tumor environments while minimizing release at physiological pH, ensuring targeted delivery. Additionally, the modified MWCNTs showed good dispersion in aqueous solutions and superior anti-cancer efficacy in vitro. The sugar-tethered nanotubes exhibited improved uptake by cancer cells, indicating effective targeting via lectin receptors. Overall, this research presents a promising approach for targeted cancer therapy, combining computational and experimental methods to develop a low-cost, non-toxic nanocarrier system with enhanced drug loading, controlled release, and targeted delivery capabilities.
In silico-guided discovery and in vitro validation of novel sugar-tethered lysinated carbon nanotubes for targeted drug delivery of doxorubicin
Chanchal Kiran Thakur, Fábio G. Martins, Chandrabose Karthikeyan, Subhasmita Bal, Chanakya Nat Kundu, N.S. Hari Narayana Moorthy, Sérgio F. Sousa
Journal of Molecular Modeling (2024) | DOI: 10.1007/s00894-024-06061-5
Abstract:
Multiwalled carbon nanotubes (MWCNTs) functionalized with lysine via 1,3-dipolar cycloaddition and conjugated to galactose or mannose are potential nanocarriers that can effectively bind to the lectin receptor in MDA-MB-231 or MCF-7 breast cancer cells. In this work, a method based on molecular dynamics (MD) simulation was used to predict the interaction of these functionalized MWCNTs with doxorubicin and obtain structural evidence that allows a better understanding of the drug loading and release process. The MD simulations showed that while doxorubicin only interacted with pristine MWCNTs through π-π stacking interactions, functionalized MWCNTs were also able to establish hydrogen bonds, suggesting that the functionalized groups improve doxorubicin loading. Moreover, the elevated adsorption levels observed for functionalized nanotubes further support this enhancement in loading efficiency. MD simulations also shed light on the intratumoral pH-specific release of doxorubicin from functionalized MWCNTs, which is induced by protonation of the daunosamine moiety. The simulations show that this change in protonation leads to a lower absorption of doxorubicin to the MWCNTs. The MD studies were then experimentally validated, where functionalized MWCNTs showed improved dispersion in aqueous medium compared to pristine MWCNTs and, in agreement with the computational predictions, increased drug loading capacity. Doxorubicin-loaded functionalized MWCNTs demonstrated specific release of doxorubicin in tumor microenvironment (pH = 5.0) with negligible release in the physiological pH (pH = 7.4). Furthermore, doxorubicin-free MWNCT nanoformulations exhibited insignificant cytotoxicity. The experimental studies yielded nearly identical results to the MD studies, underlining the usefulness of the method. Our functionalized MWCNTs represent promising non-toxic nanoplatforms with enhanced aqueous dispersibility and the potential for conjugation with ligands for targeted delivery of anti-cancer drugs to breast cancer cells.
