# Therapeutic Potential of Polymer-Coated Mesoporous Silica Nanoparticles
## 2 Polymer Coated MSNs for Cancer
These \(\sim\)300 nm particles loaded with DOX (427 mg/g) demonstrated accelerated drug release in response to low pH and exposure of NIR laser (808 nm). A superior antitumor efficacy with high safety was observed in vivo for these nanoparticles in combination with laser exposure compared to free DOX and other tested monotherapies [26]. Figure 4: Pictorial presentation of pH/HIFU dual-responsive release characteristic of DOX loaded MSN–PDA. Reproduced with permission from reference [20]. Figure 5: Schematic illustration of the progress in constructing polydopamine-coated MSN particles for drug loading and release. Adapted with permission from [25], copyright (2015) American Chemical Society. Figure 6: Graphical representation of the preparation of dual sensitive MSNs for pH/NIR-responsive chemo-photothermal therapy [26]. Alpha-tocopherolly polyethylene glycol 1000 succinate (TPGS) functionalized polydopamine-coated MSNs were also investigated for the treatment of multidrug-resistant lung cancer. An additional coating of TPGS is supposed to suppress P-glycoprotein (P-gp) meditated resistance in cancer cells. The TPGS conjugated MSNs enhanced cellular uptake in drug resistant A549 cells, thus suggesting the possibility of drug resistance reversal [27]. A polyelectrolyte complex approach was utilized by [PERSON] et al. to prepare polymer coated MSNs for the controlled delivery of curcumin. Curcumin loaded amine terminated MSNs were coated using the \"layer-by-layer\" technique by depositing oppositely charged polyelectrolytes. Further, \(\kappa\)-carrageenanan and chitosan were used as polyelectrolyte polymers due to the presence of opposite charges. Four alternating layers of coating were deposited around the particles, starting with carrageenanan followed by chitosan. The loss of anti-neoplastic activity of the drug was not observed after polymer coating, but the coating aided the sustained release of curcumin over a 24-h period [28]. Chitosan coated MSNs modified with dual targeting ligands, i.e., folic acid and hyaluronic acid, for the active targeting of DOX to tumor cells was developed by [PERSON] et al. for effective cancer therapy [29]. Chitosan coated MSNs were also employed to sustain the release of gallic acid [30]. A pH-sensitive MSN coated with poly(L-histidine) (PLH) and poly(ethylene glycol) (PEG) were synthesized by [PERSON] et al. for tumor specific release of sarafenib [31]. PLH exhibit solubility alteration based on the surrounding pH and thus, the coating provided an \"on-off\" mechanism of drug release (Figure 7). The PLH was grafted through a Michael addition reaction from thiol functionalized MSNs followed by the grafting of PEG as a hydrophilic coating. Coated MSNs with a size of 160 nm and with 20-nm thick coating were capable to trigger the release of drugs in lysosomes after the uptake of nanoparticles, due to the low lysosomal pH as evidenced by confocal microscopy in HepG2 cells. Further, nanoparticles showed negligible haemolysis activity and no visible tissue toxicity along with good anti-proliferative and tumour growth regression in vivo [31]. In another example, PEGylated lipid bilayer coated MSNs were utilized for the co-delivery of paclitaxel and curcumin. A film hydration method was used for MSN coating with 1:1.1 MSN/lipid ratio, which provided a 13-15 nm uniform coating of the surface. An in vitro drug release assay demonstrated  
Figure 7: Schematic presentation of pH responsive drug release with the aid of poly(L-histidine) (PLH) coated MSNs. Reproduced with permission from reference [31]. the sustained release of drugs with improved aqueous solubility, which persistently promoted the cytotoxic effect against breast cancer cells (7364 cells) [32]. A \"dendritic\" structured mesoporous silica nanoparticle with large pores, coated with a PEI-PEG copolymer was also explored for the controlled delivery of highly toxic tumour necrosis factor-alpha (TNF-\(\alpha\)).