Immunomodulatory zymosan/ι-carrageenan/ agarose hydrogel for targeting M2 to M1 macrophages (antitumoral)

  • RSC Adv. 2024 Apr 11;14(17):11694-11705. doi: 10.1039/d3ra06978h.
Geetha Venkatachalam  1 Jayant Giri  2 Saurav Mallik  3 Gandarvakottai Senthilkumar Arumugam  1 Manavalan Arulmani  4 Vimal Kumar Dewangan  5 Mukesh Doble  4 Zhongming Zhao  6
Affiliations
  • 1. Bioengineering and Drug Design Lab, Department of Biotechnology, Indian Institute of Technology Madras 600036 Chennai Tamilnadu India.
  • 2. Department of Mechanical Engineering, Yeshwantrao Chavan College of Engineering Nagpur India.
  • 3. Department of Pharmacology and Toxicology, University of Arizona Tucson AZ USA.
  • 4. Department of Cariology, Saveetha Dental College, SIMATS 600077 Chennai Tamilnadu India [email protected] [email protected].
  • 5. Department of Metallurgical and Materials Engineering, Indian Institute of Technology Madras 600036 Chennai India.
  • 6. McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston Houston TX USA [email protected].
Abstract

Several studies have been performed on the immunomodulatory effects of yeast β-(1,3) glucan, but there is no proper evaluation of the thermal and immunomodulating properties of zymosan (ZM). Thermogravimetry analysis indicated a 54% weight loss of ZM at 270 °C. Circular dichroism showed absorption peaks in the region of 250 to 400 nm, suggesting a helical coil β-sheet configuration. XRD showed a broad peak at 2θ of 20.38°, indicating the crystalline nature, and the size was found to be 23 nm. ZM is biocompatible and showed no toxicity against L929 and RAW 264.7 cell lines (cell viability > 90%). Immunomodulatory studies with PCR showed upregulation of M1 genes in human differentiated THP-1 macrophage cell lines, which were responsible for antitumor properties. The uptake of ZM particles inside the differentiated THP-1 macrophages and Raw 264.7 cells was confirmed (Video clip). ZM particle uptake via Dectin-1 was identified by competitive receptor blocking. Seaweed derived carrageenan/ZM/Agarose hydrogel was successfully prepared (@5 : 5 wt%) and was seen to support the growth of L929 cells (1 × 105 cells per mL) and have a higher swelling (≈250-280%). This study indicates that ZM-based hydrogel could be a potential drug carrier (Rifampicin and Levofloxacin) for targeting tumour-associated macrophages (M2).

Products