Abstract
To improve the properties of mesoporous silica nanoparticles (MSNs), the surface of MSNs was functionally modified with a pH-sensitive polymer. Using polyethylene glycol 2000-distearoyl phosphatidylethanolamine (PEG2000-DSPE) as a modifier and doxorubicin (DOX) as a model drug, the pH-sensitive mesoporous silica composite nanocarriers were formed. When the MSNs were modified with PEG2000-DSPE at (m(PEG2000-DSPE):m(MSNs) = 1:5), DOX loaded in PEG2000-DSPE-MSNs (DOX-PEG-DSPE-MSNs) possessed good physicochemical properties including the highest drug loading (loading efficiency of (76.58 ± 0.75)% and loading capacity of (9.34 ± 0.03)%), the lowest average particle size ((298 ± 2) nm) and uniform size distribution (PDI of (0.14 ± 0.01)), colloid stability (zeta potential of (− 16.5 ± 0.3) mV), large specific surface area ((512 ± 4) m2g−1) and high pore capacity ((0.29 ± 0.02) cm3g−1). A lipid bilayer formed by PEG-DSPE2000 and phospholipid coated the MSN surface, acting as the “gatekeeper” for blocking the nanopores of MSNs, preventing the leakage and burst release of DOX absorbed in the mesoporous channel. Due to the hydrolysis of the amino group of PEG-DSPE in an acidic media, the “gatekeeper” broken, leading to destabilization and destruction of the lipid bilayer, exhibiting the pH-responsive release of DOX, which was fitted with a bi-phase exponential kinetic release model. PEG-DSPE-MSNs exhibited low cytotoxicity to LO2 cells and improved the biocompatibility of MSNs. PEG-DSPE-MSNs delivered DOX to tumor cells effectively due to pH-sensitive and sustained release, contributing to the significant inhibition of Hepg-2 cells. The results confirm the benefits of surface functionalization of MSNs with PEG-DSPE, and the potential application of tumor-targeted drugs.
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Funding
This work was supported by the National Natural Science Foundation of China (No. 22078198), the Natural Science Foundation of Guangdong Province, China (NO. 2021A1515010687), and the Basic Research Project of Shenzhen city, China (NO. JCYJ20170818093429961).
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Jinglu Zhou: methodology; experiment on preparation and characterization; writing—original draft. Zhen Wen: supervision; funding acquisition; writing—review and editing. Shilun Yan: experiment on drug release. Hui Guo: data processing. Chuyue Zhou: experiment on BET; cytotoxicity and inhibition of tumor cells; writing—revision.
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Zhou, J., Wen, Z., Yan, S. et al. Preparation and release properties of pH-sensitive mesoporous silica composite nanocarriers. J Nanopart Res 24, 45 (2022). https://doi.org/10.1007/s11051-022-05433-3
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DOI: https://doi.org/10.1007/s11051-022-05433-3