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Encapsulating InsP6 with the natural polysaccharide chitosan (CS) using ionic gelation aims to improve uptake and trigger apoptosis. Encapsulation ratios were optimized and characterized by PAGE and AAS, with SEM and FTIR confirming physicochemical changes. Encapsulated InsP6 showed more efficient delivery into MCF-7 cells than free InsP6 and promoted apoptosis linked to reactive oxygen species (ROS) generation.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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to Facilitate Cellular Delivery and Programmed Cell Death in Human Breast Cancer Cells  \nIlham H. Kadhim 1, Adeolu S. Oluremi 1, Bijay P. Chhetri 2, Anindya Ghosh 2,* and Nawab Ali 1, *  \nCitation: Kadhim, I.H.; Oluremi, A.S.; Chhetri, B.P.; Ghosh, A.; Ali, N. Encapsulation of Inositol Hexakisphosphate with Chitosan via Gelation to Facilitate Cellular Delivery and Programmed Cell Death in Human Breast Cancer Cells.  \nBioengineering 2024, 11, 931 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)bioengineering11090931  \nAcademic Editors: Amol V. Janorkarand Sudip K. Das  \nReceived: 23 August 2024  \nRevised: 8 September 2024  \nAccepted: 11 September 2024  \nPublished: 17 September 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Biology, Donaghey College of Science, Engineering, Technology, and Mathematics, University of Arkansas at Little Rock, 2801 South University Avenue, Little Rock, AR 72204, USA;  \n[ihkadhim@ualr.edu](ihkadhim@ualr.edu) (I.H.K.); [asoluremi@ualr.edu](asoluremi@ualr.edu) (A.S.O.)  \n2 Department of Chemistry, Donaghey College of Science, Engineering, Technology, and Mathematics, University of Arkansas at Little Rock, 2801 South University Avenue, Little Rock, AR 72204, USA; [bpchhetri@ualr.edu](bpchhetri@ualr.edu)  \n* Correspondence: [axghosh@ualr.edu](axghosh@ualr.edu) (A.G.); [nali@ualr.edu](nali@ualr.edu) (N.A.); Tel.: +1-501-247-3248 (N.A.)  \nAbstract: Inositol hexakisphosphate (InsP 6) is the most abundant inositol polyphosphate both in plant and animal cells. Exogenous InsP 6 is known to inhibit cell proliferation and induce apoptosis in cancerous cells. However, cellular entry of exogenous InsP 6 is hindered due to the presence of highly negative charge on this molecule. Therefore, to enhance the cellular delivery of InsP 6 in cancerous cells, InsP6 was encapsulated by chitosan (CS), a natural polysaccharide, via the ionic gelation method. Our hypothesis is that encapsulated InsP 6 will enter the cell more efficiently to trigger its apoptotic effects. The incorporation of InsP 6 into CS was optimized by varying the ratios of the two and confirmed by InsP 6 analysis via polyacrylamide gel electrophoresis (PAGE) and atomic absorption spectrophotometry (AAS) . The complex was further characterized by Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR) for physicochemical changes. The data indicated morphological changes and changes in the spectral properties of the complex upon encapsulation. The encapsulated InsP 6 enters human breast cancer MCF-7 cells more efficiently than free InsP6 and triggers apoptosis via a mechanism involving the production of reactive oxygen species (ROS) . This work has potential for developing cancer therapeutic applications utilizing natural compounds that are likely to overcome the severe toxic effects associated with synthetic chemotherapeutic drugs.  \nKeywords: inositol polyphosphates; chitosan; encapsulation; apoptosis; cytotoxicity; reactive oxygen species; breast cancer  \n1. Introduction  \nInositol polyphosphates (InsPs) are naturally occurring compounds present in both plant and animal cells. They play a major role in the regulation of various cellular processes, including calcium mobilization, vesicular trafficking, cell growth and differentiation, gene expression, and programmed cell death (PCD) [1–5] . Inositol 1,4,5-trisphosphate (InsP 3) is the first water-soluble InsP produced in the cell from the membrane-bound inositol phospholipid, phosphatidylinositol 4,5-bisphosphate (P","cbCaijEnmeUpLlZI","https://ap.wps.com/l/cbCaijEnmeUpLlZI","pdf",4103485,"English","# Abstract\n# Keywords\n# Introduction","[{\"question\":\"Why is InsP6 hard to deliver into cancer cells directly?\",\"answer\":\"Exogenous InsP6 delivery is hindered by the molecule’s highly negative charge, which limits cellular entry.\"},{\"question\":\"How was InsP6 encapsulated in this study?\",\"answer\":\"InsP6 was encapsulated by chitosan using the ionic gelation method, with encapsulation ratios optimized to improve loading and delivery.\"},{\"question\":\"What evidence supports the success of encapsulation and physicochemical changes?\",\"answer\":\"InsP6 incorporation into chitosan was confirmed by InsP6 analysis via PAGE and AAS, and the complex was characterized by SEM and FTIR to detect morphological and spectral property changes.\"}]","Encapsulation of Inositol Hexakisphosphate with Chitosan via Gelation to Facilitate Cellular Delivery and Programmed Cell Death in Human Breast Cancer Cells | PDF",1790004291]