# Therapeutic Potential of Polymer-Coated Mesoporous Silica Nanoparticles
## 2 Polymer Coated MSNs for Cancer
A higher DOX release (more than 60%) was observed at pH 5.0 in the presence of glutathione (10 mM) whereas less than 20% drug was released in the absence of stimuli. The biocompatibility of blank nanocarrier was ascertained by MTT assay using HeLa cells (above 90% survivability) while DOX loaded MSNs killed 54% of the cells [38]. Iron oxide core@shell MSNs coated with pH-responsive poly(ethyleneimine) (PEI) and folic acid was fabricated for the effective delivery of erlotinib. The iron oxide core aided in tumor-targeted magnetic resonance imaging, whereas PEI was integrated to support the controlled release of the drug. Folic acid was attached to PEI by a DCC coupling reaction before coating the surface of MSNs. The resulting nanoparticles demonstrated higher toxicity in HeLa cell lines at 62.5 \(\mu\)g mL\({}^{-1}\) concentration of drug compared to free erlotinib [39]. A 30% boost in drug release was observed at pH 5.5 when compared to physiological pH for the PEI-coated MSN, compared to the non-coated MSNs for which the release behaviour under different pH conditions was not pronounced. The authors attributed this to the lower attraction between the silica surface and PEI at a lower pH, through which the silanols become less deprotonated (i.e., loses some negative charge) and any loaded drug molecules can escape through the polymer coating. We note that, in this study, the drug release behaviour was correctly compared between coated and non-coated MSNs. Thereby, especially with regard to DOX release studies, often only the release for the final MSN design is shown, this being a very frequently encountered misconception upon which \"pH-responsive release\" is claimed, even though the observed release differences are solely due to the pH-dependent solubility of DOX. We also note that, given most drug molecules are weak acids or bases, when using pH-sensitive polymer coatings such as polyamines (in essence, any polyacid or polybase) one needs to take into account the pH-induced changes a coating may impart on any loaded agents [40], thus altering their physicochemical properties. Figure 9: Schematic presentation of coated MSNs for synergistic tumor-targeted therapy [37]. \(\beta\)-cyclodextrinntin coating was employed by [PERSON] et al. to control the release of indocyanine green from mesoporous silica coated gold nanorods. Adamantane decorated dual-functional RLA peptide was then attached to modified MSNs via host-guest interaction for membrane penetration and mitochondrial targeting. Later, to impart biocompatibility and stability, a charge-switchable and anti-fouling polymer (2,3-dimethylmaleic anhydride modified chitosan oligosaccharide-b-poly(ethylene glycol)) was coated through electrostatic interaction. It was proposed that at an acidic pH of the tumor microenvironment, an electrostatic interaction between the anti-fouling polymer and RLA peptide weaken, leading the exposer of RLA for enhanced cellular internalization and mitochondrial accumulation. A combined photodynamic and photothermal therapy was demonstrated upon NIR exposure, due to the presence of indocyanine green and gold rods, leading to the excessive generation of killer ROS and subsequently resulting in tumor cell apoptosis in vitro and in vivo [41]. Poly(acrylic acid) (PAA) coated MSNs loaded with arsenic trioxide were prepared by [PERSON] et al. for targeted and pH triggered release in glioma. The MSNs were further encapsulated within liposomes coated with angioprep-2 as a targeting ligand to prepare a hybrid nanocarrier for targeted therapy (Figure 10). The amine functionalized MSNs were reacted with poly(acrylic acid) to achieve surface coating and pH sensitive properties. These 140-nm particles with negative zeta potential (\(-13\) mV) showed improved cellular uptake in HBMEC cells and blood brain barrier (BBB) permeation in an in vitro model, ascribed to the presence of the targeting peptide.