Comparison of Polydopamine-Coated Mesoporous Silica Nanorods and Spheres for the Delivery of Hydrophilic and Hydrophobic Anticancer Drugs.

Mesoporous silica nanoparticles (MSNs) have been widely studied as drug delivery systems in nanomedicine. Surface coating of MSNs have enabled them to perform efficiently in terms of bioavailability, biocompatibility, therapeutic efficacy and targeting capability. Recent studies have suggested the use of polydopamine (PDA) as a facilitative coating for MSNs that provides sustained and pH-responsive drug release, owing to the adhesive "molecular-glue" function of PDA. This further endows these hybrid MSN@PDA particles with the ability to carry large amounts of hydrophilic drugs. In this study, we expand the feasibility of this platform in terms of exploring its ability to also deliver hydrophobic drugs, as well as investigate the effect of particle shape on intracellular delivery of both a hydrophilic and hydrophobic anticancer drug. MSN@PDA loaded with doxorubicin (hydrophilic) and fingolimod (hydrophobic) was studied via a systematic in vitro approach (cellular internalization, intracellular drug distribution and cytotoxicity). To promote the cellular uptake of the MSN@PDA particles, they were further coated with a polyethylene imine (PEI)-polyethylene glycol (PEG) copolymer. Drug-loaded, copolymer-coated MSN@PDA showed effective cellular uptake, intracellular release and an amplified cytotoxic effect with both doxorubicin and fingolimod. Additionally, rods exhibited delayed intracellular drug release and superior intracellular uptake compared to spheres. Hence, the study provides an example of how the choice and design of drug delivery systems can be tuned by the need for performance, and confirms the PDA coating of MSNs as a useful drug delivery platform beyond hydrophilic drugs.

Hybrid mesoporous nanorods with deeply grooved lateral faces toward cytosolic drug delivery.

Nanocarriers with high local curvatures hold a great potential of inducing effective penetration of intracellular barriers and cytosolic delivery of membrane-impermeable drugs. However, the fine control of the sharp edges and their morphological effects inside cells remains largely unexplored. Herein, a nanocarrier system of hybrid mesoporous nanorods with six-arm star-shaped end faces and groove-patterned lateral faces was developed to maximize surface regions with high local curvatures for enhancing membrane destabilization. Specifically, twisted (right-handed) nanorods (TNR, diameter ∼120, aspect ratio 4-5) with a hexagon cross-section from a templated synthesis were modified by amino groups to promote surface coating of a wet-adhesive polymer, i.e. polydopamine (PDA). An edge-preferential deposition of PDA by local curvature effects led to the protective etching of silica, and in turn, the formation of nanorods with varying groove depths at different volumes of the aqueous coating solution. Finally, branched polyethylene imine (PEI) was grafted on the exterior surface of the nanorods for enhancing the dispersity and cellular uptake rate. As verified by elaborate in vitro investigations, the configuration of nanorods with the sharpest edges/deepest grooves can be rotated to a lying-down/upright mode in order to minimize/maximize the membrane tension during the interaction with membranes, which consequently resulted in highly efficient lysosomal escape despite the relatively lower uptake degree. The successful delivery of vorinostat (SAHA, a FDA-approved histone deacetylase inhibitor) and inhibition of cancer cells demonstrated the attractive ability of the nanocarriers in drug delivery.