Thermo- and pH-responsive targeted lipid-coated mesoporous nano silica platform for dual delivery of paclitaxel and gemcitabine to overcome HER2-positive breast cancer.

In the current study, a new monoclonal antibody conjugated dual stimuli lipid-coated mesoporous silica nanoparticles (L-MSNs) platform was developed and investigated for specific co-delivery of the paclitaxel (PTX) and gemcitabine (Gem) to cancer cells and preventing their side effects during the treatment process. First, MSNs were synthesized and then coated with as-prepared pH-, and thermo-sensitive niosomes to produce L-MSNs. For this aim, Dipalmitoylphosphatidylcholine (DPPC) was used to create thermo-sensitivity, and 1, 2-Distearoyl-sn-glycerol-3-phosphoethanolamine -Citraconic Anhydride-Polyethylene Glycol (DSPE-CA-PEG) polymers were prepared and incorporated to the lipid layer for creation of pH-sensitivity. In the next step, trastuzumab as a monoclonal antibody (mAb) was conjugated to the maleimide groups of the 1, 2-Distearoyl-sn-glycerol-3-phosphoethanolamine DSPE-polyethylene glycol (PEG)-maleimide agents in the lipid bilayer via a disulfide bond. Dynamic light scattering (DLS) and zeta potential measurements, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), and scanning electron microscopy (SEM) analyses were utilized to characterize the synthesized particles before and after surface modification. The encapsulation efficiency (EE%) and loading efficiency (LE%) of the particles were also evaluated. Additionally, the drug release study and MTT assay were done to evaluate the bioactivity potential of the fabricated platforms. The results of DLS and zeta potential measurements revealed an average size of 200 nm and a neutral zeta potential of about -1 mV for mAb-L-MSNs. Also, the FTIR spectra confirmed the formation of mAb-L-MSNs. Moreover, SEM analysis showed spherical-shaped MSNs with amorphous structure confirmed by XRD analysis, and BET test revealed ∼ 820 m

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.