Abstract
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.
Highlights
The implementation of nanotechnology in medicine for diagnostics and therapeutics to manage biological systems on the molecular scale have led to the establishment of the interdisciplinary field of nanomedicine [1]
In both cases the exposed amino groups on the surface was sufficient for successful coating of PDA, which is clearly observable in the transmission electron microscopy (TEM) images (Figure 1)
To enhance the dispersability in the complex biological environment and cellular uptake ability, both PDA-modified Mesoporous silica nanoparticles (MSNs) were further coated with an in-house produced polyethylene glycol (PEG)-polyethylene imine (PEI) copolymer (COP) [18] for cellular studies
Summary
The implementation of nanotechnology in medicine for diagnostics and therapeutics to manage biological systems on the molecular scale have led to the establishment of the interdisciplinary field of nanomedicine [1]. Mesoporous silica nanoparticles (MSNs) have been frequently used in cancer nanomedicine as drug delivery systems, imaging probes and theranostic agents due to their superior physicochemical characteristics [5,6,7] Their mesoporous structure, high surface area, tunable pore diameter and pore volumes, flexible and selective surface modification, and enhanced loading of multiple drug cargoes have boosted the development of MSN-based nanocarrier systems [8,9,10]. We found that the PDA coating improved both the drug loading capacity and drug release properties for hydrophilic drug cargo in terms of providing a sustained and acid-triggered release [15] In this follow-up study, to evaluate the shape effect we applied the same functionalization regime for rod-shaped MSNs [16] and compared the performance of these as drug carrier systems in vitro on cancer cell cultures (MDA-MB-231 and ML-1) to the earlier constructed spherical MSN@PDA particles. We evaluated spherical and rod-shaped MSNs modified with PDA as drug carriers compared to free hydrophobic and hydrophilic drugs, and examined how the difference in MSN morphology influences the performance of this promising drug delivery system
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