Folic Acid-conjugated Bovine Serum Albumin-coated Selenium-ZIF-8 Core/shell Nanoparticles for Dual Target-specific Drug Delivery in Breast Cancer

Overview

Journal Drug Deliv Transl Res

Publisher Springer

Specialty Pharmacology

Date 2024 Sep 24

PMID 39317912

Authors

Arghavan Adibifar

Maryam Salimi

Neda Rostamkhani

Zahra Karami

Abdol-Hakim Agh-Atabay

Kobra Rostamizadeh

Affiliations

Soon will be listed here.

Abstract

Methotrexate (MTX), a frequently used chemotherapeutic agent, has limited water solubility, leading to rapid clearance even in local injections. In the present study, we developed folic acid-conjugated BSA-stabilized selenium-ZIF-8 core/shell nanoparticles for targeted delivery of MTX to combat breast cancer. FT-IR, XRD, SEM, TEM, and elemental mapping analysis confirmed the successful formation of FA-BSA@MTX@Se@ZIF-8. The developed nano-DDS had a mean diameter, polydispersity index, and zeta potential of 254.8 nm, 0.17, and - 16.5 mV, respectively. The release behavior of MTX from the nanocarriers was pH-dependent, where the cumulative release percentage at pH 5.4 was higher than at pH 7.4. BSA significantly improved the blood compatibility of nanoparticles so that after modifying their surface with BSA, the percentage of hemolysis decreased from 12.67 to 5.12%. The loading of methotrexate in BSA@Se@ZIF-8 nanoparticles reduced its IC on 4T1 cells from 40.29 µg/mL to 16.54 µg/mL, and by conjugating folic acid on the surface, this value even decreased to 12.27 µg/mL. In vivo evaluation of the inhibitory effect in tumor-bearing mice showed that FA-BSA@MTX@Se@ZIF-8 caused a 2.8-fold reduction in tumor volume compared to the free MTX, which is due to the anticancer effect of selenium nanoparticles, the pH sensitivity of ZIF-8, and the presence of folic acid on the surface as a targeting agent. More importantly, histological studies and animal body weight monitoring confirmed that developed nano-DDS does not have significant organ toxicity. Taking together, the incorporation of chemotherapeutics in folic acid-conjugated BSA-stabilized selenium-ZIF-8 nanoparticles may hold a significant impact in the field of future tumor management.

References

Jolivet J, Cowan K, Curt G, Clendeninn N, Chabner B . The pharmacology and clinical use of methotrexate. N Engl J Med. 1983; 309(18):1094-104. DOI: 10.1056/NEJM198311033091805. View

Yang V, Gouveia M, Santos J, Koksch B, Amorim I, Gartner F . Breast cancer: insights in disease and influence of drug methotrexate. RSC Med Chem. 2021; 11(6):646-664. PMC: 7578709. DOI: 10.1039/d0md00051e. View

Sramek M, Neradil J, Sterba J, Veselska R . Non-DHFR-mediated effects of methotrexate in osteosarcoma cell lines: epigenetic alterations and enhanced cell differentiation. Cancer Cell Int. 2016; 16:14. PMC: 4770555. DOI: 10.1186/s12935-016-0289-2. View

Fotoohi A, Albertioni F . Mechanisms of antifolate resistance and methotrexate efficacy in leukemia cells. Leuk Lymphoma. 2008; 49(3):410-26. DOI: 10.1080/10428190701824569. View

Schweitzer B, Dicker A, Bertino J . Dihydrofolate reductase as a therapeutic target. FASEB J. 1990; 4(8):2441-52. DOI: 10.1096/fasebj.4.8.2185970. View

Bedoui Y, Guillot X, Selambarom J, Guiraud P, Giry C, Jaffar-Bandjee M . Methotrexate an Old Drug with New Tricks. Int J Mol Sci. 2019; 20(20). PMC: 6834162. DOI: 10.3390/ijms20205023. View

Chen L, Zhang T, Sun S, Ren W, Wu A, Xu H . Ultrasound-Mediated Cavitation Enhances EGFR-Targeting PLGA-PEG Nano-Micelle Delivery for Triple-Negative Breast Cancer Treatment. Cancers (Basel). 2021; 13(14). PMC: 8304156. DOI: 10.3390/cancers13143383. View

Xue C, Hu S, Gao Z, Wang L, Luo M, Yu X . Programmably tiling rigidified DNA brick on gold nanoparticle as multi-functional shell for cancer-targeted delivery of siRNAs. Nat Commun. 2021; 12(1):2928. PMC: 8131747. DOI: 10.1038/s41467-021-23250-5. View

Yadav A, Radharani N, Gorain M, Bulbule A, Shetti D, Roy G . RGD functionalized chitosan nanoparticle mediated targeted delivery of raloxifene selectively suppresses angiogenesis and tumor growth in breast cancer. Nanoscale. 2020; 12(19):10664-10684. DOI: 10.1039/c9nr10673a. View

10.

Sharifi M, Cho W, Ansariesfahani A, Tarharoudi R, Malekisarvar H, Sari S . An Updated Review on EPR-Based Solid Tumor Targeting Nanocarriers for Cancer Treatment. Cancers (Basel). 2022; 14(12). PMC: 9220781. DOI: 10.3390/cancers14122868. View

11.

Tan C, Wu J, Wen Z . Doxorubicin-Loaded MnO@Zeolitic Imidazolate Framework-8 Nanoparticles as a Chemophotothermal System for Lung Cancer Therapy. ACS Omega. 2021; 6(20):12977-12983. PMC: 8158835. DOI: 10.1021/acsomega.0c05922. View

12.

Pan Q, Chen T, Nie C, Yi J, Liu C, Hu Y . In Situ Synthesis of Ultrathin ZIF-8 Film-Coated MSNs for Codelivering Bcl 2 siRNA and Doxorubicin to Enhance Chemotherapeutic Efficacy in Drug-Resistant Cancer Cells. ACS Appl Mater Interfaces. 2018; 10(39):33070-33077. DOI: 10.1021/acsami.8b13393. View

13.

Zheng H, Zhang Y, Liu L, Wan W, Guo P, Nystrom A . One-pot Synthesis of Metal-Organic Frameworks with Encapsulated Target Molecules and Their Applications for Controlled Drug Delivery. J Am Chem Soc. 2015; 138(3):962-8. DOI: 10.1021/jacs.5b11720. View

14.

Sriraman S, Salzano G, Sarisozen C, Torchilin V . Anti-cancer activity of doxorubicin-loaded liposomes co-modified with transferrin and folic acid. Eur J Pharm Biopharm. 2016; 105:40-9. PMC: 4931959. DOI: 10.1016/j.ejpb.2016.05.023. View

15.

Kayani Z, Bordbar A, Firuzi O . Novel folic acid-conjugated doxorubicin loaded β-lactoglobulin nanoparticles induce apoptosis in breast cancer cells. Biomed Pharmacother. 2018; 107:945-956. DOI: 10.1016/j.biopha.2018.08.047. View

16.

Tong L, Chen W, Wu J, Li H . Folic acid-coupled nano-paclitaxel liposome reverses drug resistance in SKOV3/TAX ovarian cancer cells. Anticancer Drugs. 2013; 25(3):244-54. DOI: 10.1097/CAD.0000000000000047. View

17.

Lee R, Low P . Delivery of liposomes into cultured KB cells via folate receptor-mediated endocytosis. J Biol Chem. 1994; 269(5):3198-204. View

18.

Qin Y, Peng H, He X, Li W, Zhang Y . pH-Responsive Polymer-Stabilized ZIF-8 Nanocomposites for Fluorescence and Magnetic Resonance Dual-Modal Imaging-Guided Chemo-/Photodynamic Combinational Cancer Therapy. ACS Appl Mater Interfaces. 2019; 11(37):34268-34281. DOI: 10.1021/acsami.9b12641. View

19.

Hashemi-Moghaddam H, Kazemi-Bagsangani S, Jamili M, Zavareh S . Evaluation of magnetic nanoparticles coated by 5-fluorouracil imprinted polymer for controlled drug delivery in mouse breast cancer model. Int J Pharm. 2015; 497(1-2):228-38. DOI: 10.1016/j.ijpharm.2015.11.040. View

20.

Tong X, Wang Z, Sun X, Song J, Jacobson O, Niu G . Size Dependent Kinetics of Gold Nanorods in EPR Mediated Tumor Delivery. Theranostics. 2016; 6(12):2039-2051. PMC: 5039679. DOI: 10.7150/thno.17098. View