Designing Mesoporous Silica Nanoparticles to Overcome Biological Barriers by Incorporating Targeting and Endosomal Escape

Abstract

The several biological barriers that nanoparticles might encounter when administered to a patient constitute the major bottleneck of nanoparticle-mediated tumor drug delivery, preventing their successful translation into the clinic and reducing their therapeutic profile. In this work, mesoporous silica nanoparticles have been employed as a platform to engineer a versatile nanomedicine able to address such barriers, achieving (a) excessive premature drug release control, (b) accumulation in tumor tissues, (c) selective internalization in tumoral cells, and (d) endosomal escape. The nanoparticles have been decorated with a self-immolative redox-responsive linker to prevent excessive premature release, to which a versatile and polyvalent peptide that is able to recognize tumoral cells and induce the delivery of the nanoparticles to the cytoplasm via endosomal escape has been grafted. The excellent biological performance of the carrier has been demonstrated using 2D and 3D in vitro cell cultures and a tumor-bearing chicken embryo model, demonstrating in all cases high biocompatibility and cytotoxic effect, efficient endosomal escape and tumor penetration, and accumulation in tumors grown on the chorioallantoic membrane of chicken embryos.

siRNA delivery using intelligent chitosan-capped mesoporous silica nanoparticles for overcoming multidrug resistance in malignant carcinoma cells

“…1000 m 2 /g), high pore volumes (ca. 1 cm 3 /g), biocompatibility, and facile surface modification 18 , 19 . The fabrication of MSNs is cost-effective and straightforward.…”

Redox-Responsive Mesoporous Silica Nanoparticles for Cancer Treatment: Recent Updates

“…Tumors present high requirements of vitamins, which leads to the overexpression of their receptors on tumoral cells. In this sense, our group recently reported targeted redox-responsive MSNs [ 35 ]. We incorporated a redox-responsive gatekeeper based on self-immolative chemistry and further functionalize it with a peptidic molecule containing biotin (vitamin B7) for cellular targeting and histidine for inducing endosomal escape ( Figure 5 ).…”

“…( D ) The calcein assay demonstrated that only the group bearing the peptidic molecule was able to escape the endosomes. Adapted with permission from [ 35 ]. Copyright ACS, 2021.…”

Recent Advances of Nanotechnology-Facilitated Bacteria-Based Drug and Gene Delivery Systems for Cancer Treatment

“…Effective gene delivery needs to overcome several barriers, including in terms of protection against endogenous nuclease degradation, cellular uptake elevation, and endosomal avoidance [ 80 , 81 ]. However, conventional gene delivery nanoplatforms, such as mesoporous silica nanoparticles, are unable to transfer nucleic acid into host cells due to the failure of endosomal escape [ 82 ]. In this case, bacteria exhibit excellent gene delivery capabilities.…”