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Engineered (Nh2)-Mil-125(Ti)/Copolymer@Mnfe2o4 Nanocomposite for Synergistic Eradication of Cancer Cells Via Dox/Pcrispr Delivery Publisher



Safarkhani M1, 2 ; Ojaghi A2 ; Nezhad SM3 ; Daneshgar H2 ; Paivasantos AC4, 5 ; Radmanesh F6, 7 ; Bagherzadeh M2 ; Zare EN3 ; Rabiee N8, 9 ; Makvandi P10, 11
Authors
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Authors Affiliations
  1. 1. Department of Biological Sciences and Bioengineering, NanoBio High-Tech Materials Research Center, Inha University, Incheon, 402-751, South Korea
  2. 2. Department of Chemistry, Sharif University of Technology, Tehran, Iran
  3. 3. School of Chemistry, Damghan University, Damghan, 36716-45667, Iran
  4. 4. Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, 3000-548, Portugal
  5. 5. REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, 3000-548, Portugal
  6. 6. Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  8. 8. School of Engineering, Macquarie University, Sydney, 2109, NSW, Australia
  9. 9. Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, 6150, WA, Australia
  10. 10. The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Zhejiang, Quzhou, 324000, China
  11. 11. Centre of Research Impact and Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Punjab, Rajpura, 140401, India

Source: Advanced Composites and Hybrid Materials Published:2024


Abstract

The present study proposed an innovative nanocomposite aimed at enhancing gene and drug delivery for cancer treatment. The nanocomposite was composed of amine-functionalized metal–organic frameworks, (NH2)-MIL-125(Ti), conjugated to poly(aniline-co-para-phenylenediamine), and coated on manganese ferrite nanoparticles that were utilized to co-deliver the chemotherapy drug doxorubicin (DOX) and plasmid CRISPR (pCRISPR) to cancer cells. The investigation focused on whether surface modification with amine groups could improve cellular uptake and transfection efficiency. In addition, the study also utilized an engineered cell-imprinted substrate to mimic the cellular environment and enhance the delivery and expression of edited genes. The results demonstrated the proposed nanocarriers successfully co-delivered DOX and pCRISPR, indicating their potential for combination cancer therapy. Specific highlights include (1) reliable platform for multi-drug delivery based on the (NH2)-MIL-125(Ti)/poly(aniline-co-para-phenylenediamine)/MnFe2O4 nanocomposite structure; (2) hemocompatibility analysis revealed less than 1% hemolysis, pointing to biosafety; (3) amine surface modification enhanced cellular uptake up to 38.3% in A549 cells, improving transfection; (4) the cell-imprinted substrate enhanced therapeutic efficacy by promoting delivery and expression in a physiologically relevant microenvironment. Overall, this study makes significant contributions to gene delivery and expression for cancer therapy. The engineered nanocomposite, amine surface modification, and cell-mimetic substrate employ innovative strategies to augment the efficacy of combination gene and drug therapy against cancer. Graphical Abstract: [Figure not available: see fulltext.]. © 2024, The Author(s).
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