ساخت و مشخصه‌يابي نانوليپوزوم‌هاي بارگذاري شده با رگورافنيب و هدفمند شده با آنتي‌بادي مونوكلونال بواسيزومب و بررسي خواص ضد سرطاني آنها

Synthesis an‎d Characterization of Regorafenib Loaded an‎d Bevacizumab Functionalized Nanoliposomes an‎d eva‎luation of Their Anticancer Activity

زيست فناوري

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer with limited treatment options an‎d poor prognosis. In this study, a multifunctional, targeted, liposomal nanocarrier system with simultaneous therapeutic an‎d imaging (theranostic) capabilities was designed, synthesized, an‎d characterized for TNBC. Stable liposomal nanoparticles loaded with the hydro‎phobic anticancer drug Regorafenib were prepared using the thin-film hydration method (drug-to-lipid weight ratio of 1:20). Fluorescent carbon dots with a quantum yield of 27.3% an‎d size below 10 nm were synthesized via a hydrothermal method using sucrose an‎d mPDA, an‎d were loaded into the liposomes. Active targeting was achieved through covalent conjugation of bevacizumab antibody (anti-VEGF) to the liposome surface using EDC/NHS coupling chemistry an‎d palmitic acid as a lipid anchor. Nanoparticles were characterized by DLS, zeta sizer, FTIR, TEM, an‎d XRD. Results showed that the functionalized nanoliposomes loaded with Regorafenib an‎d carbon dots had a hydrodynamic size of 495 nm, a zeta potential of -44.3 mV, an‎d 100% encapsulation efficiency for Regorafenib (at 0.5 mg/mL). The presence of amide I an‎d II ban‎ds in the FTIR spectra confirmed successful antibody conjugation. The in vitro drug release profile followed first-order kinetics (R²=0.99), reaching 96.4% after 120 hours. MTT assay on human fibroblast cells demonstrated high biocompatibility of all nanoformulations (cell viability ‎>85%). While non-functionalized nanoparticles caused the death of 35.5% of MDA-MB-231 breast cancer cells, antibody-functionalized nanoparticles caused the death of 52.4% of the cancer cells, indicating improved cellular uptake via VEGF receptor-mediated endocytosis. Fluorescence imaging confirmed successful internalization of functionalized nanoparticles into the cytoplasm of cancer cells. This theranostic system, combining anti-angiogenic therapy (bevacizumab), multi-kinase inhibition (Regorafenib), an‎d fluorescence imaging capability (carbon dots), could serve as an effective theranostic platform for targeted an‎d concurrent treatment of triple-negative breast cancer.

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