Decagram-Scale Synthesis of Multicolor Carbon Nanodots: Self-Tracking Nanoheaters with Inherent and Selective Anticancer Properties

Abstract

Carbon nanodots (CDs) are a new class of carbon-based nanoparticles endowed with photoluminescence, high specific surface area, and good photothermal conversion, which have spearheaded many breakthroughs in medicine, especially in drug delivery and cancer theranostics. However, the tight control of their structural, optical, and biological properties and the synthesis scale-up have been very difficult so far. Here, we report for the first time an efficient protocol for the one-step synthesis of decagram-scale quantities of N,S-doped CDs with a narrow size distribution, along with a single nanostructure multicolor emission, high near-infrared (NIR) photothermal conversion efficiency, and selective reactive oxygen species (ROS) production in cancer cells. This allows achieving targeted and multimodal cytotoxic effects (i.e., photothermal and oxidative stresses) in cancer cells by applying biocompatible NIR laser sources that can be remotely controlled under the guidance of fluorescence imaging. Hence, our findings open up a range of possibilities for real-world biomedical applications, among which is cancer theranostics. In this work, indocyanine green is used as a bidentate SO x donor which has the ability to tune surface groups and emission bands of CDs obtained by solvothermal decomposition of citric acid and urea in N,N-dimethylformamide. The co-doping implies various surface states providing transitions in the visible region, thus eliciting a tunable multicolor emission from blue to red and excellent photothermal efficiency in the NIR region useful in bioimaging applications and image-guided anticancer phototherapy. The fluorescence self-tracking capability of SO x –CDs reveals that they can enter cancer cells more quickly than healthy cell lines and undergo a different intracellular fate after cell internalization. This could explain why sulfur doping entails pro-oxidative activities by triggering more ROS generation in cancer cells when compared to healthy cell lines. We also find that oxidative stress can be locally enhanced under the effects of a NIR laser at moderate power density (2.5 W cm–2). Overall, these findings suggest that SO x –CDs are endowed with inherent drug-independent cytotoxic effects toward cancer cells, which would be selectively enhanced by external NIR light irradiation and helpful in precision anticancer approaches. Also, this work opens a debate on the role of CD surface engineering in determining nanotoxicity as a function of cell metabolism, thus allowing a rational design of next-generation nanomaterials with targeted anticancer properties.

The Emerging Development of Multicolor Carbon Dots

“…F) Reproduced with permission. [ 104 ] Copyright 2022, American Chemical Society. G) Reproduced with permission.…”

“…The proposed findings identify graphite nitrogen as another key factor that can redshift the CD PL. In 2022, Mauro et al [104] first reported an effective method for the one-step synthesis of decagram-scale quantities of N, S-doped CDs with narrow size distribution, muticolor emission of single nanostructure, high NIR photothermal conversion efficiency, and selective reactive oxygen species production in cancer cells. In the presence of indocyanine green as a bidentate SO x donor, citric acid and urea were solvothermal decomposed.…”

“…Copyright 2017, American Chemical Society. F) Reproduced with permission [104]. Copyright 2022, American Chemical Society.…”

Sequential Drug Delivery in Targeted Cancer Therapy

“…CDs can load aromatic drugs through π–π interactions [ 62 ]. The fluorescence imaging studies showed that CD could enter cancer cells faster than normal cells, and after internalization, the CD could enhance anti-cancer drug nuclear delivery [ 27 , 63 , 64 ]. It is a suitable drug carrier in the drug delivery system.…”

Nanococktail Based on Supramolecular Glyco-Assembly for Eradicating Tumors In Vivo

“…The clinical treatment of cancer still faces numerous problems associated with unsatisfactory treatment effectiveness and damage to healthy tissues. − Phototherapy is noninvasive, exhibits minimal side effects, and is highly selective and has been established as an excellent candidate for cancer treatment. − However, treatment efficacy is often unsatisfactory when phototherapy is used, due to limits imposed by the hypoxic tumor microenvironment (TME), including less O 2 that can decrease photodynamic efficacy and the up-regulated heat shock proteins (HSPs) may cause thermal resistance. − To overcome these obstacles, nanodrug combinations called “nanococktails” comprised of photosensitizers and multiple units for the relief of hypoxia and the down-regulation of HSPs have been fabricated and utilized for cancer therapy. However, their construction remains challenging due to the utility of multiple components, requiring multistep manufacturing and potential systemic toxicity. − …”