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Author: Boyacioglu, OzgeScopus Q: Q1

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    Citation - WoS: 5
    Citation - Scopus: 6
    Clinic-Oriented Injectable Smart Material for the Treatment of Diabetic Wounds: Coordinating the Release of Gm-Csf and Vegf
    (Elsevier, 2024) Kinali, Hurmet; Kalaycioglu, Gokce Dicle; Boyacioglu, Ozge; Korkusuz, Petek; Aydogan, Nihal; Vargel, Ibrahim
    Chronic wounds are often caused by diabetes and present a challenging clinical problem due to vascular problems leading to ischemia. This inhibits proper wound healing by delaying inflammatory responses and angiogenesis. To address this problem, we have developed injectable particle-loaded hydrogels which sequentially release Granulocyte-macrophage- colony-stimulating-factor (GM-CSF) and Vascular endothelial growth factor (VEGF) encapsulated in polycaprolactone-lecithin-geleol mono-diglyceride hybrid particles. GM-CSF promotes inflammation, while VEGF facilitates angiogenesis. The hybrid particles (200 -1000 nm) designed within the scope of the study can encapsulate the model proteins Bovine Serum Albumin 65 +/- 5 % and Lysozyme 77 +/- 10 % and can release stably for 21 days. In vivo tests and histological findings revealed that in the hydrogels containing GM-CSF/VEGF-loaded hybrid particles, wound depth decreased, inflammation phase increased, and fibrotic scar tissue decreased, while mature granulation tissue was formed on day 10. These findings confirm that the hybrid particles first initiate the inflammation phase by delivering GM-CSF, followed by VEGF, increasing the number of vascularization and thus increasing the healing rate of wounds. We emphasize the importance of multi-component and sequential release in wound healing and propose a unifying therapeutic strategy to sequentially deliver ligands targeting wound healing stages, which is very important in the treatment of the diabetic wounds.
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    ACPA Prevents Lung Fibroblast-to Transformation by Reprogramming the Tumor Microenvironment through NSCLC-Derived Exosomes
    (Nature Portfolio, 2025) Boyacioglu, Ozge; Kalali, Berfin Deniz; Recber, Tuba; Gelen-Gungor, Dilek; Nemutlu, Emirhan; Eroglu, Ipek; Korkusuz, Petek; Kilic, Nedret
    Non-small cell lung cancer (NSCLC) accounts for most lung cancer cases. Current treatments often cause systemic side effects or lead to drug resistance, prompting the development of new therapies targeting tumors and related cells simultaneously. Cancer-associated fibroblasts (CAFs) are crucial stromal cells within the tumor microenvironment (TME), making them potential targets for therapy. Previously, we found that the CB1 receptor agonist ACPA has anti-tumor effects on NSCLC, inhibiting pathways such as Akt/PI3K, JNK, glycolysis, the citric acid cycle, and the urea cycle both in vitro and in vivo. We hypothesize that ACPA could enhance therapy by inhibiting the transformation of lung fibroblasts into CAFs via exosomes. Control and ACPA-treated NSCLC cell exosomes exhibited similar size, PDI, ZP, and high expression of CD9, CD63, and CD81. ACPA-treated exosomes showed reduced levels of miR-21 and miR-23. These exosomes decreased fibroblast viability within 12 h by disrupting pentose phosphate, lipid, and amino acid metabolism, and by lowering PDPN, alpha-SMA, and FAP expressions. This research highlights ACPA as a promising chemotherapeutic agent, capable of improving NSCLC treatment and reprogramming the TME with more targeted therapies.
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    Article
    Citation - WoS: 3
    Citation - Scopus: 4
    A Novel Injectable Nanotherapeutic Platform Increasing the Bioavailability and Anti-Tumor Efficacy of Arachidonylcyclopropylamide on an Ectopic Non-Small Cell Lung Cancer Xenograft Model: A Randomized Controlled Trial
    (Elsevier, 2025) Boyacioglu, Ozge; Varan, Cem; Bilensoy, Erem; Aykut, Zaliha Gamze; Recber, Tuba; Nemutlu, Emirhan; Korkusuz, Petek
    Rapid progressing non-small cell lung adenocarcinoma (NSCLC) decreases treatment success. Cannabinoids emerge as drug candidates for NSCLC due to their anti-tumoral capabilities. We previously reported the controlled release of Arachidonylcyclopropylamide (ACPA) selectively targeting cannabinoid 1 (CB1) receptor in NSCLC cells in vitro. Hydrophobic polymers like polycaprolactone (PCL) offer prolonged circulation time and slower drug clearance which is suitable for hydrophobic molecules like ACPA. Thus, the extended circulation time with enhanced bioavailability and half-life of nanoparticular ACPA is crucial for its therapeutic performance in the tumor area. We assumed that a novel high technology-controlled release system increasing the bioavailability of ACPA compared to free ACPA could be transferred to the clinic when validated in vivo. Plasma profile of ACPA and ACPA-loaded PCL-based nanomedicine by LC-MS/MS and complete blood count (CBC) was assessed in wild-type Balb/c mice. Tumor growth in nanomedicine-applied NSCLC-induced athymic nude mice was assessed using bioluminescence imaging (BLI) and caliper measurements, histomorphometry,immunohistochemistry, TUNEL assay, and Western blot on days 7-21. Injectable NanoACPA increased its systemic exposure to tissues 5.5 times and maximum plasma concentration 6 times higher than free ACPA by substantially improving bioavailability. The potent effect of NanoACPA lasted for at least two days on ectopic NSCLC model through Akt/PI3K, Ras/MEK/Erk, and JNK pathways that diminished Ki-67 proliferative and promoted TUNEL apoptotic cell scores on days 7-21. The output reveals that NanoACPA platform could be a chemotherapeutic for NSCLC in the clinic following scale-up GLP/GMP-based phase trials, owing to therapeutic efficacy at a safe low dose window.