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Hyaluronic Acid Layered Chimeric Nanoparticles: TargetingnMAPK-PI3K Signaling Hub in Colon Cancer Cells 透明质酸层状嵌合纳米颗粒：靶向结肠癌细胞nMAPK-PI3K信号中枢

Figshare Pub Date : 2017-11-14 DOI: 10.1021/acsomega.7b01315.s001

Sandeep Palvai (1542823), Meenu Mahesh Kuman (4590376), Poulomi Sengupta (4590373), Sudipta Basu (1542820)

{"title":"Hyaluronic Acid Layered Chimeric Nanoparticles: TargetingnMAPK-PI3K Signaling Hub in Colon Cancer Cells","authors":"Sandeep Palvai (1542823), Meenu Mahesh Kuman (4590376), Poulomi Sengupta (4590373), Sudipta Basu (1542820)","doi":"10.1021/acsomega.7b01315.s001","DOIUrl":"https://doi.org/10.1021/acsomega.7b01315.s001","url":null,"abstract":"Colon cancer has emerged as one of the most devastating diseases in thenwhole world. Mitogen-activated protein kinase (MAPK)-phosphatidylinsitol-3-kinasen(PI3K) signaling hub has gained lots of attention due to its deregulationnin colon cancer cells. However, selective targeting of oncogenic MAPK-PI3Knhub in colon cancer has remained highly challenging, hence it hasnmostly been unexplored. To address this, we have engineered a hyaluronicnacid layered lipid-based chimeric nanoparticle (HA-CNP) consistingnof AZD6244 (MAPK inhibitor), PI103 (PI3K inhibitor), and cisplatinn(DNA impairing drug) ratiometrically in a single particle. Electronnmicroscopy (field emission scanning electron microscopy and atomicnforce microscopy) and dynamic light scattering were utilized to characterizenthe size, shape, morphology, and surface charge of the HA-CNPs. Fluorescentnconfocal laser scanning microscopy and flow cytometry analysis confirmednthat HA-CNPs were taken up by HCT-116 colon cancer cells by mergingnof clathrin and CD44 receptor-mediated endocytosis along with macropinocytosisnto home into acidic organelles (lysosomes) within 1 h. A gel electrophoresisnstudy evidently established that HA-CNPs simultaneously inhibitednMAPK-PI3K signaling hub with DNA damage in HCT-116 cells. These HA-CNPsnstalled the cell cycle into G0/G1 phase, leading to induction of apoptosisn(early and late) in colon cancer cells. Finally, these HA-CNPs exertednremarkable cytotoxicity in HCT-116 colon cancer cells at 24 h comparednto that of the free triple drug cocktail as well as HA-coated dualndrug-loaded nanoparticles without showing any cell death in healthynL929 fibroblast cells. These HA-coated CNPs have potential to be translatedninto clinics as a novel platform to perturb various oncogenic signalingnhubs concomitantly toward next-generation targeted colon cancer therapy.","PeriodicalId":521646,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147883181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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