Effect of different sizes of chitosan on the NLRP3 inflammasome.
On the contrary, chitosan of molecular weight lesser than 29.2 kDa acts in a pro-inflammatory manner by increasing phosphorylation of JNK of the MAPK pathway, enhancing NF-κB activation and iNOS expression causing an increase in the levels of NO, and increasing the production of TNF-α and IL-6 by binding to CR3, TLR4 and CD14 on macrophages. All these factors combined increase the activation of the NLRP3 inflammasome
[79][22]. In a study on Hep2 and RD cell lines, chitosan showed cytotoxicity against these cell lines, and had a better IC than chitin and irradiated chitin
[64][7].
Studies on chitosan often only characterise MW or DDA in high detail and leave out the other and fail to fully characterise the features of chitosan. This can lead to ambiguity in results. Studies have found that DDA does not make a difference in the immunoreactive properties of chitosan
[76][19]. It is also suggested that endotoxin presence can interfere with the properties of chitosan. Another factor to consider is that as the DDA of chitosan approaches 100% its solubility increases that can play a role in being more bioavailable and affecting its properties during delivery
[80][23].
Further treatment of the chitosan polymer can lead to the formation of chitosan nanoparticles and chitosan scaffolds. Although the role of DDA in the effect of chitosan polymer affecting the immune system has contradictory and ambiguous results, there are studies investigating the properties of the scaffolds and the nanoparticle showing a correlation between DDA and the properties of the material.
2.3. Effect of Chitooligosaccharides
Chitooligosaccharides (COS) are degraded products of chitosan by enzymatic or chemical methods. Chitosan, like its precursor is still insoluble and not easily absorbed into the body. However, COS is soluble and easily absorbed by the gastrointestinal tract, after which it affects the target cells. This implies that COS can be utilised for a myriad of applications by retaining the bioactive properties of chitosan
[84][24].
As explored previously, the antitumoral effect of COS is attributed to recruitment of T-cells and immunoregulation.
We propose tTh
at alongside this, theere is an inflammation/inflammasome-dependent manner by which COS and variations of COS are able to affect cancer
[5][4]. It is likely that a combination of the two of these factors leads to the potent anti-cancer properties that these molecules possess.
This hypothesis can be further supported by studies conducted on the types of cancers described previously. A study conducted by Shen et al. showed that the use of COS with 23.99 kDa molecular weight, markedly reduced the proliferation of HepG2 cells by inhibiting the NF-κB
[85,86][25][26]. Studies were conducted on colorectal cancer cells showing that utilisation of COS between 1 and 3 kDa reduced pro-inflammatory cytokine production by the inhibition of MM2 and iNOS, which led to a preventative effect
[84][24].