Scaling-up of carbon dots hydrothermal synthesis from sugars in a continuous flow microreactor system for biomedical application as <i>in vitro</i> antimicrobial drug nanocarrier
Creators: name: Supajaruwong, Siriboon
name: Porahong, Sirawich
name: Wibowo, Agung
name: Yu, Yu-Sheng
name: Khan, Mohd Jahir
name: Pongchaikul, Pisut
name: Posoknistakul, Pattaraporn
name: Laosiripojana, Navadol
name: Wu, Kevin C.-W.
name: Sakdaronnarong, Chularat
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Space Science
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Marine Biology
subject: Infectious Diseases
subject: FOS: Health sciences

description: Carbon dots (CDs) are a new class of nanomaterials exhibiting high biocompatibility, water solubility, functionality, and tunable fluorescence (FL) property. Due to the limitations of batch hydrothermal synthesis in terms of low CDs yield and long synthesis duration, this work aimed to increase its production capacity through a continuous flow reactor system. The influence of temperature and time was first studied in a batch reactor for glucose, xylose, sucrose and table sugar precursors. CDs synthesized from sucrose precursor exhibited the highest quantum yield (QY) (175.48%) and the average diameter less than 10 nm (~6.8 ± 1.1 nm) when synthesized at 220°C for 9 h. For a flow reactor system, the best condition for CDs production from sucrose was 1 mL min<sup>−1</sup> flow rate at 280°C, and 0.2 MPa pressure yielding 53.03% QY and ~ 6.5 ± 0.6 nm average diameter (6.6 mg min<sup>−1</sup> of CDs productivity). CDs were successfully used as ciprofloxacin (CP) nanocarrier for antimicrobial activity study. The cytotoxicity study showed that no effect of CDs on viability of L-929 fibroblast cells was detected until 1000 µg mL<sup>−1</sup> CDs concentration. This finding demonstrates that CDs synthesized via a flow reactor system have a high zeta potential and suitable surface properties for nano-theranostic applications. In this work, we focused on a scaled-up production of CDs from various sugar monomers from a batch hydrothermal synthesis to a continuous flow microreactor system. From the result, the novelties of the work are as follows: Successful CDs’ production with high capacity of 6.6 mg CDs min<sup>−1</sup> was achieved from sucrose in a continuous system at the reaction time of only 4.4 min at moderate temperature (280–350°C) and pressure (&lt;2 MPa).The developed process was greatly superior than the process in a batch reactor which provided only 0.19 mg CDs min<sup>−1</sup> when the reaction time was 9 or 12 h.The produced CDs were subsequently used as <i>in vitro</i> antimicrobial drug nanocarrier due to its high zeta potential indicating its high stability in aqueous solution, thus led to enhanced CP loading capacity.The pH-controlled released of CP from CP@CDs conjugates worked efficiently toward gram-positive and gram-negative bacterial strains, namely, <i>Staphylococcus aureus, Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>.<i>In vitro</i> cytotoxicity against mammalian fibroblast cells (L-929 cells) was also carried on. The findings demonstrated that CDs potentially serve as a new type of nanocarrier with good functionality, FL properties and markedly high biocompatibility for further nanomedicine and nanotherapeutic.Their utilization is potentially combined with photonic property such as bioimaging for rapid <i>in vivo</i> monitoring of targeted intracellular drug-release toward specific cells, sensitive neurodegeneration detection as well as photo-responsive anti-inflammatory wound healing application. Successful CDs’ production with high capacity of 6.6 mg CDs min<sup>−1</sup> was achieved from sucrose in a continuous system at the reaction time of only 4.4 min at moderate temperature (280–350°C) and pressure (&lt;2 MPa). The developed process was greatly superior than the process in a batch reactor which provided only 0.19 mg CDs min<sup>−1</sup> when the reaction time was 9 or 12 h. The produced CDs were subsequently used as <i>in vitro</i> antimicrobial drug nanocarrier due to its high zeta potential indicating its high stability in aqueous solution, thus led to enhanced CP loading capacity. The pH-controlled released of CP from CP@CDs conjugates worked efficiently toward gram-positive and gram-negative bacterial strains, namely, <i>Staphylococcus aureus, Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>. <i>In vitro</i> cytotoxicity against mammalian fibroblast cells (L-929 cells) was also carried on. The findings demonstrated that CDs potentially serve as a new type of nanocarrier with good functionality, FL properties and markedly high biocompatibility for further nanomedicine and nanotherapeutic. Their utilization is potentially combined with photonic property such as bioimaging for rapid <i>in vivo</i> monitoring of targeted intracellular drug-release toward specific cells, sensitive neurodegeneration detection as well as photo-responsive anti-inflammatory wound healing application.