4.7 Article

Alginate/κ-carrageenan oral microcapsules loaded with Agaricus bisporus polysaccharides MH751906 for natural killer cells mediated colon cancer immunotherapy

Journal

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 205, Issue -, Pages 385-395

Publisher

ELSEVIER
DOI: 10.1016/j.ijbiomac.2022.02.058

Keywords

Agaricus bisporus; NK cells; Alginate; Kappa-carrageenan; Microcapsules; Cancer immunotherapy

Funding

  1. Academy of Scientific Research & Technology (ASRT), Cairo, Egypt, and Scientists for Next Generation program (SNG)

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This study investigates the use of novel mushroom polysaccharides formulated in Alginate/kappa carrageenan microcapsules to activate gut resident natural killer cells (NK) for immunotherapeutic effect against colon cancer. The microcapsules demonstrate superior stability and controlled release, and when activated by human NK cells, exhibit significant cytotoxic effects on colon cancer cells leading to apoptosis. The molecular mechanism behind this effect involves down regulation of anti-apoptotic genes and up regulation of pro-apoptotic gene expression.
The current study explores the effect of the extracted novel Mushroom polysaccharides and its formulation onto Alginate (Alg.)/kappa carrageenan microcapsules to exert immunotherapeutic effect upon activating gut resident natural killer cells (NK) against colon cancer. The extracted polysaccharides of Agaricus bisporus MH751906 was microcapsulated in Alg/kappa-carrageenan microcapsules as an oral delivery system for colon cancer. The micro capsule is characterized by SEM, FTIR, Raman and TGA; and showed a superior acidic stability, controlled release, and thermal stability at high temperature with higher hydrogel swelling rate in colon-mimicking pH. Upon activation of human NK cells with microcapsules ((NK)-N-A cells), a significant increase in CD16(+)CD56(+) NK cell populations were recorded. These activated NK cells showed 74.09% cytotoxic effects against human colon cancer Caco-2 cells where majority of cancer cell populations arrested at G0/G1 phase leading to apoptosis. The apoptotic molecular mechanism induced by (NK)-N-A cells on Caco-2 treated cells is through down regulations of both BCL2 and TGF surviving genes and up regulation in IkappaB-alpha gene expression. Therefore, this novel polysaccharides-alginate/kappa-carrageenan microcapsules can be used as an oral targeted delivery system for colon cancer immunotherapy.

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