Construction And Antitumor Activity Study Of A Mesoporous Silica-Based Targeted Drug Delivery System

The design and development of different strategies based on mesoporous silica nanomaterials?MSNs?for tumor therapy have become a vital part of Drug Delivery Systems?DDS?.Single chemotherapy has greatly limited the therapeutic effect of drug-resistant tumors,but synergistic treatment with photothermal therapy?PTT?and photodynamic therapy?PDT?could not only improve anticancer activity,but also reduce the side effects of chemotherapy drugs.We have respectively coupled the active targeting ligand molecules,such as folic acid and triphenylphosphonium,to mesoporous silica to achieve targeted transport of nanocarriers,wherein folate-modified mesoporous silica nanoparticles could recognize folate receptor in breast cancer cells,and deliver more chemotherapy drugs and other guest molecules to tumor sites.This paper was mainly carried out from two aspects.The first one was that NIR stimulus-responsive core–shell type nanoparticles delivered doxorubicin?DOX?and photosensitizer indocyanine green?ICG?based on photothermal conversion for enhanced antitumor efficacy through chemo-photothermal therapy.The other one was that the magnetic mesoporous silica nanocarriers step-by-step targeted to transport DOX and catalase inhibitor?AT?to the tumor sites,producing highly toxic reactive oxygen species?ROS?and synergistic chemotherapy to improve anticancer efficacy under the iron ion-mediated Fenton reaction.Although this type of photodynamic therapy did not involve photosensitizers,the producing reactive oxygen species depended on fewer conditions under biochemical reactions and the therapeutic effect was significant.A novel core–shell type nanoparticle?CSNP?was designed here to target co-delivery of DOX and ICG to tumor sites by the aid of NIR induced photothermal conversion effect for the purpose of synergistic chemo-photothermal cancer therapy.The electrostatically self-assembled CSNPs were prepared by amino-functionalized mesoporous silica nanoparticles as the positive inner core and folate modified lecithin as the negative outer shell.The obtained MSNs by sol–gel process showed well-dispersed nanospheres with uniform size of 43 nm,however they possessed large pore size to guarantee a high drug loading capacity.In addition,specific concentration?40?g/mL?ICG-loaded CSNPs indicated a desired photothermal conversion efficiency achieving an appropriate temperature up to 45°C.In vitro cell assay,the prepared CSNPs showed outstanding inhibitory efficiency?2.07%cell viability in 24 h?on MCF-7 cells.Iron oxide core-shell mesoporous silica nanoparticles?Fe3O4@MSN?were prepared via the hydrolysis of tetraethyl orthosilicate on the surface of the Fe3O4 nanoparticles,and further conjugated with folate and mitochondrial targeting triphenylphosphonium to form magnetic mesoporous silica nanocarriers?Fe3O4@MSN-TPP/PEG-FA?.Reactive oxygen species promoting synergistic combined chemotherapy platform was designed by Fe3O4@MSN-TPP/PEG-FA encapsulating DOX and AT for cancer therapy.DOX could stimulate activation of nicotinamide adenine dinucleotide phosphate oxidases,which reacted oxygen into superoxide radical that could be further triggered to produce hydrogen peroxide?H2O2?by the superoxide dismutase enzyme.AT,as a catalase inhibitor,was employed to inhibit the catalase activity to save the production of H2O2.Further,H2O2 was catalyzed with the help of Fe²⁺/Fe³⁺released from Fe₃O₄@MSN to form highly toxic free hydroxyl radicals by Fenton reactions,which could induce the cell death by synergistic DOX therapy.In vitro assay,the prepared DOX/AT-loaded Fe3O4@MSN-TPP/PEG-FA showed remarkable inhibition efficiency?3.23%cell viability?on MGC-803 cells.