Targeted Delivery of Doxorubicin Using Transferrin-Conjugated Carbon Dots for Cancer Therapy

Abstract

A transferrin receptor (TfR)-targeted nanodrug [green fluorescence emission carbon dot (GCD)−polyethylene glycol (PEG)−transferrin (Tf)@doxorubicin (Dox)] for cancer therapy was developed by functionalizing GCDs with PEG, Tf, and Dox. GCDs were synthesized by the one-step hydrothermal method, followed by conjugating PEG and Tf by covalent bonds and loading Dox by electrostatic interactions. The nanodrug exhibits high stability under neutral conditions and effectively releases Dox at pH of 5.5. GCD−PEG−Tf@Dox can be selectively internalized by TfR-overexpressed tumor cells (MCF-7 and K150) via receptor-mediated endocytosis and further release Dox to the nuclei. As a result, GCD−PEG−Tf@Dox exhibits significant lethality to tumor cells (MCF-7 and K150) but greatly reduced toxicity to normal cells [Chinese hamster ovary cell line (CHO)] compared with free Dox. In vivo studies have confirmed that GCD−PEG−Tf@Dox can effectively inhibit tumor proliferation with negligible side effects.

Synthesis Processes, Photoluminescence Mechanism, and the Toxicity of Amorphous or Polymeric Carbon Dots

“…For example, functionalization can be used to create CDs with targeted cellular affinity and lower overall toxicity. 45 Li et al developed CDs functionalized with PEG and transferrin (Tf) to load doxorubicin (Dox), a widely used chemotherapeutic drug used for various cancers. The role of Tf was to ensure that the CDs were internalized only by cancerous cells.…”

“…(A) GQDs functionalized with ligands that target cancerous cell types can be used for Dox drug delivery and reduce toxicity to noncancerous cells. Figure reprinted with permission from ref . Copyright 2021 American Chemical Society.…”

“…The inherent toxicity of the ligands used for functionalization and how the physiochemical characteristics impact the CD affinity for cells both play a role in final CD toxicity. However, as with the chemical composition, there are certainly exceptions and measures to be taken to reduce toxicity, such as functionalization with multiple ligands and incorporating ligands that target specific cells. , The specific physiochemical characteristics that impact PCD toxicity need to be further investigated to confidently determine what properties are directly correlated with toxicity.…”

Carbon Dot Therapeutic Platforms: Administration, Distribution, Metabolism, Excretion, Toxicity, and Therapeutic Potential

“…However, attachment of toxic ligands (including therapeutics with toxic side effects) to CD supports has, in some cases, shown increased bioavailability and reduced toxicity of these compounds. [168] Despite the overwhelming evidence for CDs possessing high biocompatibility, [11,169,170] deviations to this observation have been documented. Dominant factors which have been shown to bring upon undesirable bodily responses include i) multiple-dosing regimens, ii) activation by extended light irradiation, iii) HD sizes above 6 nm, iv) high positive charge, and v) concentrated localized charge densities.…”

Review of Carbon Dot-Based Drug Conjugates for Cancer Therapy

“…Effect of transferrin-conjugated CDs on cancer cells for cellular imaging and selective killing of cancer cells. Reprinted from ref . Copyright 2021 American Chemical Society…”