CD44 Targeting of Cisplatin-Loaded Hyaluronic Acid-Modified Mesoporous Silica Nanoparticles for Lung Adenocarcinoma: Synthesis, Characterization, In Vitro and In Vivo Evaluation

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dc.contributor.authorGuler, Cem
dc.contributor.authorGelen, S. Sacide
dc.contributor.authorSanci, Ebru
dc.contributor.authorBuhur, Aylin
dc.contributor.authorTikir, H. Ece
dc.contributor.authorNalbantsoy, Ayse
dc.contributor.authorGuner, Adem
dc.date.accessioned2026-04-25T14:20:29Z
dc.date.available2026-04-25T14:20:29Z
dc.date.issued2026
dc.departmentSinop Üniversitesi
dc.description.abstractBackground/Objectives: Cisplatin (CDDP) is widely used in the treatment of non-small cell lung cancer (NSCLC); however, its clinical efficacy is limited by severe systemic toxicity. Hyaluronic acid (HA) modification enables the targeting of CD44-overexpressing cancer cells, enhances biocompatibility, provides controlled drug release, and prolongs systemic circulation. This study aimed to develop high-molecular-weight hyaluronic acid-modified, cisplatin-loaded mesoporous silica nanoparticles (HA-MSN-CDDP) to selectively target CD44-overexpressing lung adenocarcinoma cells. Methods: HA-MSN-CDDP nanoparticles were synthesized via the sol-gel method and characterized by FTIR, DLS, SEM, and TEM methods. Antitumor efficacy was evaluated using both in vitro and in vivo xenograft lung cancer models in mice. Results: HA modification enabled controlled and sustained release of cisplatin from the HA-MSN-CDDP drug delivery system. Through HA-mediated receptor-dependent endocytosis, the nanoparticles exhibited enhanced cellular uptake and selective cytotoxicity toward CD44-positive cells. HA-MSN-CDDP significantly reduced the cytotoxic, genotoxic, and oxidative stress effects of free cisplatin on healthy cells while markedly enhancing apoptosis in A549-Luc-C8 cells. The system showed excellent hemocompatibility, supporting its potential for intravenous use. In vivo, HA-MSN-CDDP effectively suppressed tumor growth, mitigated lipid peroxidation, and preserved antioxidant enzyme activities (SOD and CAT) in major organs. Histological analyses confirmed reduced cisplatin-induced nephrotoxicity. Conclusions: HA-MSN-CDDP demonstrates strong potential as a targeted chemotherapeutic platform for NSCLC, combining high antitumor efficacy with reduced systemic toxicity.
dc.description.sponsorshipEge University Scientific Research Projects [FM-NAP-2023-28473]; TUBITAK 2211C National PhD Scholarship Programs; 100/2000 CoHE PhD Scholarship Program
dc.description.sponsorshipThis study is based on the PhD thesis of Dr. Cem Guler, who was supported by TUBITAK 2211C National PhD Scholarship Programs (Priority area: Biotechnological Drug Technologies) and 100/2000 CoHE PhD Scholarship Program (Priority area: Molecular Pharmacology and Drug Research). This study was funded by Ege University Scientific Research Projects (FM-ONAP-2023-28473).
dc.identifier.doi10.3390/pharmaceutics18020171
dc.identifier.issn1999-4923
dc.identifier.issue2
dc.identifier.orcid0000-0002-7483-0184
dc.identifier.pmid41754914
dc.identifier.scopus2-s2.0-105031298736
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.3390/pharmaceutics18020171
dc.identifier.urihttps://hdl.handle.net/11486/8607
dc.identifier.volume18
dc.identifier.wosWOS:001700153800001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMdpi
dc.relation.ispartofPharmaceutics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20260420
dc.subjectcisplatin
dc.subjectmesoporous silica nanoparticles
dc.subjecthyaluronic acid
dc.subjectCD44
dc.subjectdrug delivery system
dc.subjectactive targeting
dc.subjectlung cancer
dc.titleCD44 Targeting of Cisplatin-Loaded Hyaluronic Acid-Modified Mesoporous Silica Nanoparticles for Lung Adenocarcinoma: Synthesis, Characterization, In Vitro and In Vivo Evaluation
dc.typeArticle

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