Effects of Doxorubicin Delivery by Nitrogen-Doped Graphene Quantum Dots on Cancer Cell Growth: Experimental Study and Mathematical Modeling

Abstract

With 18 million new cases diagnosed each year worldwide, cancer strongly impacts both science and society. Current models of cancer cell growth and therapeutic efficacy in vitro are time-dependent and often do not consider the Emax value (the maximum reduction in the growth rate), leading to inconsistencies in the obtained IC50 (concentration of the drug at half maximum effect). In this work, we introduce a new dual experimental/modeling approach to model HeLa and MCF-7 cancer cell growth and assess the efficacy of doxorubicin chemotherapeutics, whether alone or delivered by novel nitrogen-doped graphene quantum dots (N-GQDs). These biocompatible/biodegradable nanoparticles were used for the first time in this work for the delivery and fluorescence tracking of doxorubicin, ultimately decreasing its IC50 by over 1.5 and allowing for the use of up to 10 times lower doses of the drug to achieve the same therapeutic effect. Based on the experimental in vitro studies with nanomaterial-delivered chemotherapy, we also developed a method of cancer cell growth modeling that (1) includes an Emax value, which is often not characterized, and (2), most importantly, is measurement time-independent. This will allow for the more consistent assessment of the efficiency of anti-cancer drugs and nanomaterial-delivered formulations, as well as efficacy improvements of nanomaterial delivery.

Complexation Nanoarchitectonics of Carbon Dots with Doxorubicin toward Photodynamic Anti-Cancer Therapy

“…Thus, zeta-potential values confirmed an increase in the charge of the Cdots1:x as the nitrogen-doping levels increased at acid pH, suggesting that the positively charged surface of Cdots/DOX complexes might interact with the negatively charged cell membranes through electrostatic interactions and affect cancer cells in their growth [ 42 , 43 ], and the positive charge of Cdots/DOX complexes depends on the x value in Cdot1:x/DOX as known from the zeta-potential values in Figure 3 Ab. Some works in the literature have reported that although the case of lower IC 50 of DOX than of Cdots/DOX occurred for MGC-803 cells and the inverse case was true for MCF-7 cells, their IC 50 was always larger than that of the present report for HeLa cells (see Table S2 ) [ 7 , 44 , 45 ]. These tendencies may also be reasoned by the strong electrostatic interaction of Cdots/DOX with HeLa cells.…”

ZnO@ZIF-8 Nanoparticles as Nanocarrier of Ciprofloxacin for Antimicrobial Activity

“…The smaller the size of the NPs is, the greater the surface area of these NPs is, and, consequently, the greater the interaction with the cellular components of the bacteria is, so the antimicrobial activity becomes greater and faster [ 4 ]. On the other hand, ZnO NPs have exceptional physicochemical characteristics, such as their luminescent properties, making it possible to use these NPs to monitor the biodistribution of drugs in the body in addition to the presence of hydroxyl terminals on the surface of the NPs, allowing for their conjugation with different molecules [ 5 , 6 ].…”

Graphene family in cancer therapy: recent progress in cancer gene/drug delivery applications

“…DOX is an anticancer medication that works by destroying cell DNA via interfering with topoisomerase-II (TOP2)-mediated DNA repair and creating free radicals that cause cell membrane damage. 156 Functionalized GQDs have been employed by Li 2022 et al 157 as a nanocarrier for colon cancer therapy. GQDs were grafted with PEG and PEI and furnished with DOX and GFP plasmid and formed a star-shaped nanocarrier.…”