Publication:
Cetuximab-Ag2S quantum dots for fluorescence imaging and highly effective combination of ALA-based photodynamic/chemo-therapy of colorectal cancer cells

dc.contributor.coauthorMohammad Hadi, Layla
dc.contributor.coauthorYaghini, Elnaz
dc.contributor.coauthorLoizidou, Marilena
dc.contributor.coauthorMacRobert, Alexander J.
dc.contributor.departmentDepartment of Chemistry
dc.contributor.departmentDepartment of Physics
dc.contributor.departmentGraduate School of Sciences and Engineering
dc.contributor.departmentKUYTAM (Koç University Surface Science and Technology Center)
dc.contributor.kuauthorAcar, Havva Funda Yağcı
dc.contributor.kuauthorBayır, Ali
dc.contributor.kuauthorDemirci, Gözde
dc.contributor.kuauthorHashemkhani, Mahshid
dc.contributor.kuauthorMuti, Abdullah
dc.contributor.kuauthorSennaroğlu, Alphan
dc.contributor.schoolcollegeinstituteCollege of Sciences
dc.contributor.schoolcollegeinstituteGRADUATE SCHOOL OF SCIENCES AND ENGINEERING
dc.contributor.schoolcollegeinstituteResearch Center
dc.date.accessioned2024-11-09T11:50:20Z
dc.date.issued2021
dc.description.abstractColorectal cancer (CRC) has a poor prognosis and urgently needs better therapeutic approaches. 5-Aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) based photodynamic therapy (PDT) is already used in the clinic for several cancers but not yet well investigated for CRC. Currently, systemic administration of ALA offers a limited degree of tumour selectivity, except for intracranial tumours, limiting its wider use in the clinic. The combination of effective ALA-PDT and chemotherapy may provide a promising alternative approach for CRC treatment. Herein, theranostic Ag2S quantum dots (AS-2MPA) optically trackable in near-infrared (NIR), conjugated with endothelial growth factor receptor (EGFR) targeting Cetuximab (Cet) and loaded with ALA for PDT monotherapy or ALA/5-fluorouracil (5FU) for the combination therapy are proposed for enhanced treatment of EGFR(+) CRC. AS-2MPA-Cet exhibited excellent targeting of the high EGFR expressing cells and showed a strong intracellular signal for NIR optical detection in a comparative study performed on SW480, HCT116, and HT29 cells, which exhibit high, medium and low EGFR expression, respectively. Targeting provided enhanced uptake of the ALA loaded nanoparticles by strong EGFR expressing cells and formation of higher levels of PpIX. Cells also differ in their efficiency to convert ALA to PpIX, and SW480 was the best, followed by HT29, while HCT116 was determined as unsuitable for ALA-PDT. The therapeutic efficacy was evaluated in 2D cell cultures and 3D spheroids of SW480 and HT29 cells using AS-2MPA with either electrostatically loaded, hydrazone or amide linked ALA to achieve different levels of pH or enzyme sensitive release. Most effective phototoxicity was observed in SW480 cells using AS-2MPA-ALA-electrostatic-Cet due to enhanced uptake of the particles, fast ALA release and effective ALA-to-PpIX conversion. Targeted delivery reduced the effective ALA concentration significantly which was further reduced with codelivery of 5FU. Delivery of ALA via covalent linkages was also effective for PDT, but required a longer incubation time for the release of ALA in therapeutic doses. Phototoxicity was correlated with high levels of reactive oxygen species (ROS) and apoptotic/necrotic cell death. Hence, both AS-2MPA-ALA-Cet based PDT and AS-2MPA-ALA-Cet-5FU based chemo/PDT combination therapy coupled with strong NIR tracking of the nanoparticles demonstrate an exceptional therapeutic effect on CRC cells and excellent potential for synergistic multistage tumour targeting therapy.
dc.description.fulltextYES
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue35
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuTÜBİTAK
dc.description.sponsorshipNewton-Katip Çelebi Fund
dc.description.sponsorshipBritish Council
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TÜBİTAK)
dc.description.versionPublisher version
dc.description.volume13
dc.identifier.doi10.1039/d1nr03507j
dc.identifier.eissn2040-3372
dc.identifier.embargoNO
dc.identifier.filenameinventorynoIR03187
dc.identifier.issn2040-3364
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85115617479
dc.identifier.urihttps://doi.org/10.1039/d1nr03507j
dc.identifier.wos691694200001
dc.keywordsAminolevulinic Acid
dc.keywordsPhotodynamic therapy
dc.keywordsActinic keratosis
dc.language.isoeng
dc.publisherRoyal Society of Chemistry (RSC)
dc.relation.grantno216Z131
dc.relation.grantno334995
dc.relation.ispartofNanoscale
dc.relation.urihttp://cdm21054.contentdm.oclc.org/cdm/ref/collection/IR/id/9949
dc.subjectChemistry
dc.subjectNanoscience and nanotechnology
dc.subjectMaterials science
dc.subjectPhysics
dc.subjectScience and technology
dc.titleCetuximab-Ag2S quantum dots for fluorescence imaging and highly effective combination of ALA-based photodynamic/chemo-therapy of colorectal cancer cells
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorAcar, Havva Funda Yağcı
local.contributor.kuauthorBayır, Ali
local.contributor.kuauthorHashemkhani, Mahshid
local.contributor.kuauthorDemirci, Gözde
local.contributor.kuauthorMuti, Abdullah
local.contributor.kuauthorSennaroğlu, Alphan
local.publication.orgunit1College of Sciences
local.publication.orgunit1GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
local.publication.orgunit1Research Center
local.publication.orgunit2KUYTAM (Koç University Surface Science and Technology Center)
local.publication.orgunit2Department of Chemistry
local.publication.orgunit2Department of Physics
local.publication.orgunit2Graduate School of Sciences and Engineering
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