Preparation And Property Of Polyelectrolyte Assembled Microcapsules/Microspheres For PH Sensing And Targeting

Compared with layer-by-layer (LbL) assembly technology, polyamine-salt aggregates (PSA) method to fabricate microcapsules shows great advantages. The easy fabrication process, tremendous flexibility in building materials and tunable size make the PSA capsules good candidates for biomedical applications. The intracellular location of the vectors is very important for the drug delivery efficiency. Capsules with pH sensing property can provide real-time measurement of localized pH to visualize the trafficking of microcapsules.In this paper, SiO2 nanoparticles were deposited on the poly(allylamine hydrochloride)/multivalent anionic salt aggregates (PAH-Cit) followed by silicic acid treatment, the generated microcapsules are stable in a wide pH range (3.0-8.0). pH sensitive dye and pH insensitive dye were simultaneously labeled on the capsules, which enabled the ratiometric pH sensing. Due to the rough and positively charged surface, the microcapsules could be internalized by several kinds of cells naturally. Real-time measurement of intracellular pH in several living cells showed that the capsules were all located in acidic organelles after being taken up.Then N-(3-Dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC) /succinimide (NHS) was used to chemically crosslink the PSA aggregates. Poly-L-lysine (PLL) and hyaluronic acid (HA) were alternatively assembled on the crosslinked aggregates surface to generate stable microspheres. Flow cytometry (FCM) results showed that HA modified microspheres can target HeLa cells as the percentage of uptook number in HeLa cells was nearly twice as much as in NIH 3T3 cells. Confocal laser scanning microscope was further used to monitor the localized pH. The results showed that microspheres were successfully ingested into HeLa cells and localized in acidic environment. But only very few microspheres adhered on the surface of NIH 3T3 cells and almost no spheres were internalized into cells.