Chitosan and Its Derivative-Based Nanoparticles in Gastrointestinal Cancers: Molecular Mechanisms of Action and Promising Anticancer Strategies

Table 2

Anticancer activities of CS and its derivatives and molecular mechanisms of action in GI cancers.

GI cancer type	CS/its derivative	Biological features	Molecular/cellular mechanisms of action	Outcome	References
Esophageal cancer	CSNPs (e.g., CSP-Cr-NCs, TMC-IRN-SLNs)	Nanocarriers with high bioavailability, solubility, stability, sensitivity, and specificity both hydrophilic and hydrophobic	Modulate the metastatic phenotype of cancer-associated fibroblast cells by using various cellular and molecular markers, increasing ROS production in tumor cells, inducing apoptosis	Inhibition of cell growth and proliferation, antimetastatic effect	[79, 82, 83]
Gastric cancer	CMC	High viscosity, large hydrodynamic volume, low toxicity, and biocompatibility	Inhibit the proliferation, tube formation, and migration of gastric tumor cells by upregulating and downregulating various factors	Antiproliferative and antimetastatic effect	[93, 94]
	CSNPs (e.g., HTCCMNPs, HTCCMNPs)	Nanocarriers with high bioavailability, solubility, stability, sensitivity, and specificity both hydrophilic and hydrophobic	Inducing cell cycle arrest at the G2/M phase, promoting apoptosis and autophagy, decreasing generation of ROS, inhibiting cancer cell proliferation, and suppressing their invasion change in the expression level of various factors	Cell senescence, inhibition of cell growth and proliferation, antimetastatic effect	[95–101]
Hepatocellular carcinoma	CMC	High viscosity, large hydrodynamic volume, low toxicity, and biocompatibility	Antitumor, antiproliferative, decreased generation of ROS, inhibit metastasis through the upregulation of metastasis-related proteins	Antiproliferative and antimetastatic effect	[102, 103]
	CSNPs	Nanocarriers with heightened bioavailability, sensitivity, and specificity while decreasing pharmacological toxicity	Disrupt cellular membranes and induce apoptosis	Inhibition of tumor growth and proliferation	[104, 105]
Colorectal cancer	CSNPs (e.g., CS-TPP/IL-12, LMWC/COS)	Nanocarriers with high bioavailability, solubility, stability, sensitivity, and specificity both hydrophilic and hydrophobic	Inducing apoptosis, attenuating the toxicity of IL-12, inhibiting tumor metastasis by inducing NK cells and T-cell infiltration, inhibiting NO and iNOS	Cell death and antiproliferative and antimetastatic effect	[106, 107]
Pancreatic cancer	CSNPs (e.g., MiaPaCa-2, DEMC)	Nanocarriers with high bioavailability, solubility, stability, sensitivity, and specificity both hydrophilic and hydrophobic	Altering intracellular signaling pathways, antiproliferative, antiapoptotic, anti-invasive, and antimigratory properties	Antiproliferative and antimetastatic effect	[108–117]

CSNPs, CS nanoparticles; CMC, carboxymethyl CS; CSNPs, colloidal superstructures of nanoparticles; CSP-Cr-NCs, CS-sodium alginate-polyethylene glycol-crocin nanocomposites; HTCCMNPs, N-((2-hydroxy-3-trimethylammonium) propyl) CS chloride (HTCC)/alginate-encapsulated Fe₃O₄ magnetic nanoparticles; HTCCMNPs, high-temperature carbonized cellulose magnetic nanoparticles; MiaPaCa-2, metformin encapsulated in O-carboxymethyl CS (OCMCS) NPs on pancreatic cancer cells; DEMC, N,N-diethyl N-methyl CS; DDS, drug delivery system; ROS, reactive oxygen species.