Fig. 5
Development of a dual delivery carrier for OX plus IND using lipid-bilayer coated mesoporous silica nanoparticles (OX/IND-MSNP). a Schematic to show the structure of OX-laden MSNP, in which the drug is trapped by a lipid bilayer (LB) that contains the IND-PL. This leads to stable entrapment of OX in the pores, with IND-PL trapped in the bilayer. The coating procedure provides uniform and instantaneous sealing of the particle pores. The development of an optimized lipid coating mixture (75% IND-PL, 20% cholesterol, and 5% DSPE-PEG2K), is described in Supplementary Fig. 8a. The CryoEM picture shows a spherical MSNP core and its coated lipid bilayer. CryoEM imaging of ~100 particles demonstrated that the average particle size of the MSNP core was ~70 nm, while that of the LB-coated particles was ~83 nm (including a 6.5 nm thick lipid bilayer). CryoEM images for the control OX/LB-MSNP particles demonstrated a particle size of ~82 nm (Supplementary Fig. 8d). Low-magnification cryoEM images are provided in Supplementary Fig. 8c, d. b IVIS optical imaging to study the biodistribution of IV OX/IND-MSNP in orthotopic-implanted KPC tumors in mice (n = 6) at the indicated time points. Dylight 680-labeled DMPE was used for NIR imaging. Ex vivo imaging was performed for tumor, heart, liver, spleen, kidneys, and lung tissue collected from the animals 24 and 48 h post injection. c A separate experiment evaluated the PK profile of OX/IND-MSNP in orthotopic tumor-bearing mice (n = 6), receiving single IV injection to deliver the equivalent 5 mg/kg OX and 50 mg/kg IND. Free OX served as a control. Plasma was collected after 0.083, 2, 8, 24 and 48 h, and used for the analysis of IND, IND-PL, and silicon (Si) content, as described in the methods section. d The tumors and major organs were collected after 48 h for analysis of the tissue content of OX, IND, and Si. The results are expressed as mean ± SEM. # p < 0.001, (ANOVA).
