Sustained in Vitro Delivery of Metformin-Loaded Mesoporous Silica Nanoparticles for Delayed Senescence and Stemness Preservation of Adipose-Derived Stem Cells Publisher



Dadashpour M^{1, 2} ; Mahmoudi H³ ; Rahimi Z⁴ ; Janghorbanian Poodeh R⁵ ; Mousazadeh H⁶ ; Firouziamandi A⁷ ; Yazdani Y⁸ ; Nezami Asl A⁹ ; Akbarzadeh A^{10, 11}
Source: Journal of Drug Delivery Science and Technology Published:2023

Abstract

Background: The goal of the present work was to assess the effectiveness of metformin-loaded, amine-modified mesoporous silica nanoparticles (MET@MSNs-NH2) on human adipose-derived stem cells' (hADSCs') sustained in vitro proliferation without causing cellular senescence or aging. Methods: MET loading and characterization of the MET@MSNs-NH2 was conducted through FE-SEM, TEM, BET, and FTIR. Enhanced metabolic activity, as well as the hADSCs proliferation on MET@MSNs-NH2 after 21 days of cell culture, were assessed by colorimetric MTT technique and PicoGreen dsDNA assay, respectively. Also, the analyses of stem cell aging, cell migration, cell multidirectional differentiation capacity were successfully evaluated. Results: The findings of MTT assay and PicoGreen method also shown an enhanced rate of metabolic activity and duplication of hADSCs that were seeded on the MET@MSNs-NH2 after 14 and 21 days of cell culture in comparison with the other groups. Besides, the human telomerase reverse transcriptase (hTERT) and telomerase expression was meaningfully raised in hADSCs cultured on MET@MSNs-NH2 in comparison with the control group. Moreover, MET@MSNs-NH2 could be protected ADSCs cell activities by minimizing cell aging, improving cell migration, and differentiation possible during the long-term proliferation of ADSCs. Conclusions: Our finding confirmed that MET@MSNs-NH2 is capable of controlled release of MET and serves as a novel platform for the prohibition of cellular senescence of ADSCs, supporting a useful approach to simplify ADSC-based therapy. © 2023 Elsevier B.V.