Abstract
Objective: A simple pH and redox dual stimuli-responsive diketopyrrolopyrrole (DPP)-Cu2+ complexes gated mesoporous silica nanoparticles (MSN) were prepared for precise drug delivery and controlled drug release.
Method: MSN was prepared by sol-gel method and then laminated. Carboxylic acid (CA)-Pyrrolo[3,4-c] pyrrole-1,4-dione, 2,5-dihydro-3,6-di-2-pyridinyl (PyDPP) was grafted onto the surface of amino-functionalized MSN (MSN-NH2) through a simple amide reaction and then complexed with Cu2+ to form gated molecules after doxorubicin (DOX) loading.
Results: Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Low-angle X-ray diffraction (XRD) showed that MSN with uniform particle size (100 nm) and porous structure was successfully prepared. The prepared MSN, MSN- NH2, and MSN-DPP were fully characterized by Zeta potential, Fourier transforms infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption- desorption. High DOX-loading capacity (18.22%) and encapsulation efficiency (89.16%) were achieved by optimizing the mass ratio of MSN to DOX. Release studies showed that the gated molecules of our designed DPP-Cu2+ complexes had a good blocking effect under physiological conditions (the cumulative release rate of drugs within 24 hours was only 4.18%) and responded well to the pH and redox glutathione (GSH) dual stimuli. In vitro cytotoxicity assay showed that MSN-DPP-Cu2+ had good biocompatibility in both Hep G2 cells and L02 cells (the relative cell viability of both cells within 48 hours was above 97%), and the MSN-DPP-Cu2+@DOX could be triggered for efficient drug release in Hep G2 cells.
Conclusion: The MSN-DPP-Cu2+ described in this research may be a good delivery system for the controlled release of antitumor drugs and can provide a potential possibility for clinical application in the future.
[http://dx.doi.org/10.1111/j.1749-6632.1991.tb27261.x]
[http://dx.doi.org/10.1002/med.20238] [PMID: 21287572]
[http://dx.doi.org/10.1021/acsami.5b08460] [PMID: 26553405]
[http://dx.doi.org/10.1002/adhm.202100639] [PMID: 34165909]
[http://dx.doi.org/10.1016/j.drudis.2021.05.010] [PMID: 34058372]
[http://dx.doi.org/10.1021/acs.accounts.1c00544] [PMID: 34850635]
[http://dx.doi.org/10.1016/j.drudis.2020.03.009] [PMID: 32283193]
[http://dx.doi.org/10.1016/j.msec.2020.111626] [PMID: 33321667]
[http://dx.doi.org/10.1016/j.addr.2021.04.005] [PMID: 33845040]
[http://dx.doi.org/10.1016/j.jconrel.2021.02.016] [PMID: 33609621]
[http://dx.doi.org/10.1016/j.addr.2016.06.018] [PMID: 27426411]
[http://dx.doi.org/10.1016/j.jconrel.2019.08.032] [PMID: 31472191]
[http://dx.doi.org/10.1016/j.drudis.2021.01.030] [PMID: 33549529]
[http://dx.doi.org/10.1080/17425247.2019.1554647] [PMID: 30496697]
[http://dx.doi.org/10.1016/j.cis.2020.102317] [PMID: 33212389]
[http://dx.doi.org/10.2147/IJN.S299448] [PMID: 33688185]
[http://dx.doi.org/10.1039/C9SC06260B] [PMID: 34084342]
[http://dx.doi.org/10.1016/j.colsurfb.2019.03.019] [PMID: 30991215]
[http://dx.doi.org/10.1016/j.colsurfb.2018.11.071] [PMID: 30522009]
[http://dx.doi.org/10.1021/acsami.9b04142] [PMID: 31195793]
[http://dx.doi.org/10.1080/17425247.2019.1598375] [PMID: 30897978]
[http://dx.doi.org/10.1002/adbi.201800020]
[http://dx.doi.org/10.1002/mabi.202000034] [PMID: 32329202]
[http://dx.doi.org/10.1007/s12274-020-2736-6]
[http://dx.doi.org/10.1016/j.ijbiomac.2019.12.265] [PMID: 31911174]
[http://dx.doi.org/10.1016/j.ijbiomac.2018.09.058] [PMID: 30219514]
[http://dx.doi.org/10.1016/j.colsurfb.2019.04.023] [PMID: 31035057]
[http://dx.doi.org/10.1016/j.jcis.2020.09.073] [PMID: 33011414]
[http://dx.doi.org/10.1016/j.actbio.2022.02.033] [PMID: 35235863]
[http://dx.doi.org/10.1016/j.colsurfb.2022.112408] [PMID: 35168105]
[http://dx.doi.org/10.1021/jacs.1c06559] [PMID: 34632780]
[http://dx.doi.org/10.3390/nano12122068]
[http://dx.doi.org/10.1016/j.actbio.2021.10.028] [PMID: 34715367]
[http://dx.doi.org/10.1021/acsami.1c03211] [PMID: 33956444]
[http://dx.doi.org/10.1016/j.actbio.2020.12.045] [PMID: 33359766]
[http://dx.doi.org/10.1016/j.talanta.2021.122893] [PMID: 34736709]
[http://dx.doi.org/10.1007/s00604-021-05095-3] [PMID: 34837525]
[http://dx.doi.org/10.1016/j.jcis.2021.06.142] [PMID: 34225072]
[http://dx.doi.org/10.1021/acsami.1c04953] [PMID: 33913684]
[http://dx.doi.org/10.1016/j.snb.2018.03.026]
[http://dx.doi.org/10.1016/j.snb.2017.01.037]
[http://dx.doi.org/10.1021/acs.analchem.6b04258] [PMID: 28192984]
[http://dx.doi.org/10.1016/j.jlumin.2018.12.046]
[http://dx.doi.org/10.1002/anie.201407537] [PMID: 25370127]
[http://dx.doi.org/10.1039/C7NR07204J] [PMID: 29177329]
[http://dx.doi.org/10.1016/j.apsb.2019.08.003] [PMID: 31867161]
[http://dx.doi.org/10.1021/acs.analchem.7b00989] [PMID: 28376620]
[http://dx.doi.org/10.1021/mp200613y] [PMID: 22738645]
[http://dx.doi.org/10.1016/j.colsurfb.2017.01.010] [PMID: 28088015]
[http://dx.doi.org/10.1007/s10853-018-2363-8]
[http://dx.doi.org/10.1002/adfm.201605985]
[http://dx.doi.org/10.1021/acsami.5b00752] [PMID: 25893819]