Engineering Mitochondriotropic Carbon Dots for Targeting Cancer Cells

Abstract

Aiming to understand and enhance the capacity of carbon dots (CDs) to transport through cell membranes and target subcellular organelles—in particular, mitochondria—a series of nitrogen-doped CDs were prepared by the one-step microwave-assisted pyrolysis of citric acid and ethylenediamine. Following optimization of the reaction conditions for maximum fluorescence, functionalization at various degrees with alkylated triphenylphosphonium functional groups of two different alkyl chain lengths afforded a series of functionalized CDs that exhibited either lysosome or mitochondria subcellular localization. Further functionalization with rhodamine B enabled enhanced fluorescence imaging capabilities in the visible spectrum and allowed the use of low quantities of CDs in relevant experiments. It was thus possible, by the appropriate selection of the alkyl chain length and degree of functionalization, to attain successful mitochondrial targeting, while preserving non-toxicity and biocompatibility. In vitro cell experiments performed on normal as well as cancer cell lines proved their non-cytotoxic character and imaging potential, even at very low concentrations, by fluorescence microscopy. Precise targeting of mitochondria is feasible with carefully designed CDs that, furthermore, are specifically internalized in cells and cell mitochondria of high transmembrane potential and thus exhibit selective uptake in malignant cells compared to normal cells.

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

“…Antiseptic Picloxydine, Octenidine, Miramistin [470], Polyhexamethylene Biguanide [471] Insecticide Parathione [132], Fipronil [472], Dibutyl succinate [203] Former Drugs d-sotalol, cisapride [473], piracetam (status varies among countries) [474], ORG-12962 [199] Toxic xenobiotic Polybrominated-diphenyl-ethers [475], Bisphenol [476], Perfluoroalkyls [477], nitroaromatic explosives (TNT,2A, and 24DA) [478][479][480][481], 1,4-Dioxane [482], Benzo[a]pyrene [483] Nanomaterials Graphene [484][485][486][487], Carbon Dots [488], Phosphorene Oxide Nanosheets [489], Gold Nanoparticles [490][491][492], Titanium Dioxide Nanoparticles [493], Generic Nanoparticles (coarse grained) [494], Fullerene [495][496][497][498], Previous reviews [499] Polymers Poly(ethyleneoxide)-Poly-(propylene oxide) [500], polyethylenimine [501], Poloxamer [502,503], Pluronics [504,505], poly(ethyleneglycol)-desferrioxamine/ gallium [506], PEG functionalized with carbochydrates [507] and peptides…”

Advances in the design and use of carbon dots for analytical and biomedical applications

“…These CDs localized to the mitochondria in MCF-7 cells as revealed by Mito-tracker and had excellent photostability that permitted long-term imaging of mitochondria dynamics [142]. Kaminari et al [143] also designed CDs that selectively localized to the mitochondria. These CDs generated with o-phenylenediamine precursors and conjugated with TPP were capable of tracking mitochondria in MCF-7 cells as shown by MitoTracker.…”

Recent Advances in Carbon Dots for In Vitro/Vivo Fluorescent Bioimaging: A Mini-Review

“…(D) N-CDs internalization in live MDA-MB-231 cells. ( Kaminari et al, 2021 ); (E) (a) Uptake and distribution of WCDs in zebrafish embryos; (b) The distribution of WCDs in zebrafish larvae; (c) Fluorescence microscopy images of uptake of WCDs in zebrafish growth cycle ( Zonglin Liu et al, 2021 ). (F) (a) Confocal images of wild-type zebrafish showing the injection route, heart, blood stream, CNS and observation area (central canal of spinal cord).…”

“…CDs can be a new mitochondrial imaging probe, a series of N-CDs were prepared by Kaminari et al The N-CDs exhibit subcellular mitochondrial localization and compared to known mitochondrial probes, multi-functionalized N-CDs exhibit superior photostability, stable long-term mitochondrial imaging, and cell compatibility with apoptotic labeling potential ( Figure 1D ). Their uptake depends on mitochondrial membrane potential and induces their preferential localization in malignant cells, which is expected to serve as a carrier for mitochondria-targeted delivery of anticancer drugs ( Kaminari et al, 2021 ). Guo et al synthesized fluorescent CDs that could observe cell viability in situ by simple microwave-assisted synthesis.…”