Zorba, Basak IsilBoyacioglu, OezgeCaglayan, TugbaRecber, TubaNemutlu, EmirhanEroglu, IpekKorkusuz, Petek2024-07-052024-07-05202400898-21041532-239410.1080/08982104.2023.22620252-s2.0-85173733893https://doi.org/10.1080/08982104.2023.2262025https://hdl.handle.net/20.500.14411/2165KORKUSUZ, PETEK/0000-0002-7553-3915; Boyacioglu, Ozge/0000-0001-5240-8209; Recber, Tuba/0000-0001-8257-7628Curable approaches for primary osteosarcoma are inadequate and urge investigation of novel therapeutic formulations. Cannabinoid ligands exert antiproliferative and apoptotic effect on osteosarcoma cells via cannabinoid 2 (CB2) or transient receptor potential vanilloid type (TRPV1) receptors. In this study, we confirmed CB2 receptor expression in MG63 and Saos-2 osteosarcoma cells by qRT-PCR and flow cytometry (FCM), then reported the reduction effect of synthetic specific CB2 receptor agonist CB65 on the proliferation of osteosarcoma cells by WST-1 (water-soluble tetrazolium-1) and RTCA (real-time impedance-based proliferation). CB65 revealed an IC50 (inhibitory concentration) for MG63 and Saos-2 cells as 1.11 x 10(-11) and 4.95 x 10(-11) M, respectively. The specific antiproliferative effect of CB65 on osteosarcoma cells was inhibited by CB2 antagonist AM630. CB65 induced late apoptosis of MG63 and Saos-2 cells at 24 and 48 h, respectively by FCM when applied submaximal concentration. A novel CB65 liposomal system was generated by a thin film hydration method with optimal particle size (141.7 +/- 0.6 nm), polydispersity index (0.451 +/- 0.026), and zeta potential (-10.9 +/- 0.3 mV) values. The encapsulation efficiency (EE%) of the CB65-loaded liposomal formulation was 51.12%. The CB65 and CB65-loaded liposomal formulation releasing IC50 of CB65 reduced proliferation by RTCA and invasion by scratch assay and induced late apoptosis of MG63 and Saos-2 cells, by FCM. Our results demonstrate the CB2 receptor-mediated antiproliferative and apoptotic effect of a new liposomal CB65 delivery system on osteosarcoma cells that can be used as a targeted and intelligent tool for bone tumors to ameliorate pediatric bone cancers following in vivo validation.eninfo:eu-repo/semantics/closedAccessOsteosarcomacannabinoidCB65liposomeapoptosisArticleQ2342274287WOS:00108150710000137740901