# Therapeutic Potential of Polymer-Coated Mesoporous Silica Nanoparticles
## 2 Polymer Coated MSNs for Cancer
The PEI-PEG coated MSN led to the pH dependent sustained release of TNF-\(\alpha\), reduced its systemic toxicity, and demonstrated the efficient regression of 3D melanoma spheroids in a time and dose-dependent manner [33]. PEG coated MSNs were also utilized for chemo-photodynamic therapy using chlorin-e6 as a photosensitizer. As such, (3-aminopropyl) triethyoxysilane (APTES) conjugated with chlorine-e6 was employed to prepare MSNs and DOX was loaded into the pores. PEG was later conjugated onto MSNs surface via oxygen sensitive bis(alkylthio)alkene linker to control the drug release by light irradiation. On irradiation of red light (660 nm), chlorin-e6 generates killer ROS, which along with initiating cell apoptosis, also cleaved the oxygen sensitive linker leading to PEG de-shielding and allowing the accelerated release of DOX for chemotherapy. The superior anticancer effect of MSNs was further demonstrated in vivo, in which a significant anticancer effect was observed in mice treated with modified MSNs when irradiated with a red light. In addition, the photodynamically triggered endosomal escape of the carrier by light irradiation owing to the presence of chlorin-e6 was successfully confirmed in vitro [34]. A triple responsive drug delivery system was fabricated by applying a thermo-responsive polymer poly(N-isopropylacrylamide) (PNIPAAm) coating to MSN via disulfide linkage. In addition to the temperature and redox responsiveness, iron oxide nanoparticles were incorporated inside MSNs to make them triple responsive (i.e., magnetic field). DOX was encapsulated as an anticancer agent and its release was controlled via a magnetic field, temperature, and the presence of a reductive environment (Figure 8) [35]. Dual responsive MSNs were also utilized to co-deliver evodiamine and berberine (herbal anticancer drugs) by [PERSON] et al. Poly(NIPAM-co-MA) was used as a dual sensitive polymer to seal the pores, which imparted pH and thermo-responsive drug release characteristics. MSNs were further coated with DSPE-PEG\({}_{2000}\)-modified lipid bilayer to enhance the biocompatibility of the nanoparticles. An accelerated release of drugs was observed at pH 5.0 and at high temperature (41 \({}^{\circ}\)C). The dual drug loaded nanoparticles having a 1:6 ratio of evodiamine:berberine led to an increase in apoptosis rate and was found to be almost similar to taxol to inhibit tumor growth in vivo, but with fewer side effects [36]. Synergistic cancer starvation and chemotherapy was attempted by [PERSON] et al. using a poly (L-lysine) and hyaluronic acid (HA) coated MSN for the co-delivery of glucose oxidase and paclitaxel (PTX) (Figure 9). Poly (L-lysine) was attached to the MSN surface via a pH-sensitive benzoic-imine bond to  
Figure 8: Schematic representation of a triple responsive release mechanism of drug from PNIPAAm coated magnetic MSNs. Reproduced with permission from reference [35]. prevent drug leakage and to facilitate endosomal escape. An additional coating of HA was performed to avoid the toxic effect of poly (L-lysine) due to the presence of amine groups, consequently increasing biocompatibility and simultaneously HA is acting as a targeting ligand. It was observed that the surface coating of HA enhanced the cellular uptake of nanoparticles via CD44 receptor-dependent mechanism in HepG2 cells. A significant reduction in tumor growth was observed in vivo with modified MSNs compared to PTX alone. It was suggested that the glucose oxidase elevated the toxic H2O2 level by oxidizing intratumoral glucose (which block the energy supply to tumor cells) and thus demonstrated remarkable anticancer activity along with PTX [37]. Sodium alginate coated MSNs was developed for dual responsive controlled release of DOX. Sodium alginate was attached to MSNs via disulphide linkage to add reduction sensitive property, whereas alginate itself exhibit pH responsive characteristics.