pH-Sensitive doxorubicin delivery using zinc oxide nanoparticles as a rectified theranostic platform: in vitro anti-proliferative, apoptotic, cell cycle arrest and in vivo radio-distribution studies.

التفاصيل البيبلوغرافية
العنوان:	pH-Sensitive doxorubicin delivery using zinc oxide nanoparticles as a rectified theranostic platform: in vitro anti-proliferative, apoptotic, cell cycle arrest and in vivo radio-distribution studies.
المؤلفون:	Swidan MM; Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, PO13759, Cairo, Egypt. dr_swidan@yahoo.com., Marzook F; Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, PO13759, Cairo, Egypt. dr_swidan@yahoo.com., Sakr TM; Radioactive Isotopes and Generator Department, Hot Labs Center, Egyptian Atomic Energy Authority, PO13759, Cairo, Egypt.
المصدر:	Journal of materials chemistry. B [J Mater Chem B] 2024 Jun 27; Vol. 12 (25), pp. 6257-6274. Date of Electronic Publication: 2024 Jun 27.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101598493 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-7518 (Electronic) Linking ISSN: 2050750X NLM ISO Abbreviation: J Mater Chem B Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Cambridge : Royal Society of Chemistry
مواضيع طبية MeSH:	Doxorubicin/pharmacology , Doxorubicin/chemistry , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Theranostic Nanomedicine* , Cell Cycle Checkpoints*/drug effects, Humans ; Animals ; Mice ; Hydrogen-Ion Concentration ; MCF-7 Cells ; Nanoparticles/chemistry ; Tissue Distribution ; Antibiotics, Antineoplastic/pharmacology ; Antibiotics, Antineoplastic/chemistry ; Dextrans/chemistry ; Drug Carriers/chemistry ; Technetium/chemistry ; Particle Size
مستخلص:	Despite enormous advancements in its management, cancer is the world's primary cause of mortality. Therefore, tremendous strides were made to produce intelligent theranostics with mitigated side effects and improved specificity and efficiency. Thus, we developed a pH-sensitive theranostic platform composed of dextran immobilized zinc oxide nanoparticles, loaded with doxorubicin and radiolabeled with the technetium-99m radionuclide ( ^99m Tc-labelled DOX-loaded ZnO@dextran). The platform measured 11.5 nm in diameter with -12 mV zeta potential, 88% DOX loading efficiency and 98.5% radiolabeling efficiency. It showed DOX release in a pH-responsive manner, releasing 93.1% cumulatively at pH 5 but just 7% at pH 7.4. It showed improved intracellular uptake, which resulted in a high growth suppressive effect against MCF-7 cancer cells as compared to the free DOX. It boasted a 4 times lower IC 50 than DOX, indicating its significant anti-proliferative potential (0.14 and 0.55 μg ml ^-1 , respectively). The in vitro biological evaluation revealed that its molecular mode of anti-proliferative action included downregulating Cdk-2, which provoked G1/S cell cycle arrest, and upregulating both the intracellular ROS level and caspase-3, which induced apoptosis and necrosis. The in vivo experiments in Ehrlich-ascites carcinoma bearing mice demonstrated that DOX-loaded ZnO@dextran showed a considerable 4-fold increase in anti-tumor efficacy compared to DOX. Moreover, by utilizing the diagnostic radionuclide ( ^99m Tc), the radiolabeled platform ( ^99m Tc-labelled DOX-loaded ZnO@dextran) was in vivo monitored in tumor-bearing mice, revealing high tumor accumulation (14% ID g ^-1 at 1 h p.i.) and reduced uptake in non-target organs with a 17.5 T/NT ratio at 1 h p.i. Hence, ^99m Tc-labelled DOX-loaded ZnO@dextran could be recommended as a rectified tumor-targeted theranostic platform.
المشرفين على المادة:	80168379AG (Doxorubicin) SOI2LOH54Z (Zinc Oxide) 0 (Antibiotics, Antineoplastic) 0 (Dextrans) 0 (Drug Carriers) 7440-26-8 (Technetium)
تواريخ الأحداث:	Date Created: 20240607 Date Completed: 20240627 Latest Revision: 20240627
رمز التحديث:	20240627
DOI:	10.1039/d4tb00615a
PMID:	38845545
قاعدة البيانات:	MEDLINE

الوصف
تدمد:	2050-7518
DOI:	10.1039/d4tb00615a