Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures

Abstract

Intracellular drug delivery by mesoporous silica nanoparticles (MSNs) carrying hydrophilic and hydrophobic fluorophores as model drug cargo is demonstrated on 2D cellular and 3D tumor organoid level. Two different MSN designs, chosen on the basis of the characteristics of the loaded cargo, were used: MSNs with a surface-grown poly(ethylene imine), PEI, coating only for hydrophobic cargo and MSNs with lipid bilayers covalently coupled to the PEI layer as a diffusion barrier for hydrophilic cargo. First, the effect of hydrophobicity corresponding to loading degree (hydrophobic cargo) as well as surface charge (hydrophilic cargo) on intracellular drug release was studied on the cellular level. All incorporated agents were able to release to varying degrees from the endosomes into the cytoplasm in a loading degree (hydrophobic) or surface charge (hydrophilic) dependent manner as detected by live cell imaging. When administered to organotypic 3D tumor models, the hydrophilic versus hydrophobic cargo-carrying MSNs showed remarkable differences in labeling efficiency, which in this case also corresponds to drug delivery efficacy in 3D. The obtained results could thus indicate design aspects to be taken into account for the development of efficacious intracellular drug delivery systems, especially in the translation from standard 2D culture to more biologically relevant organotypic 3D cultures.

Directing cellular responses in a nanocomposite 3D matrix for tissue regeneration with nanoparticle-mediated drug delivery

“…Similarly, PEI modified nanoparticles had strong colocalization with the TRITC channel and a smaller spread of intracellular release. Our previous reports have pinpointed the presence of MSN-PEIs in endosomes at 72 h after incubation supporting the necessity of the longer timeframe for intracellular release [ 77 ] and the release rate can be further promoted by utilizing ACA or SUC modification for more efficient cargo delivery in a shorter period in this case.…”

Encapsulation and Controlled Release of Resveratrol Within Functionalized Mesoporous Silica Nanoparticles for Prostate Cancer Therapy

“…Therefore, silica nanoparticles have been recently used in a human trial for patients with melanoma and have shown strong implications in cancer diagnosis (Phillips et al, 2014). An interesting feature of MSNs is that it can encapsulate both hydrophilic and hydrophobic molecules with similar loading efficiency owing to extensively available pores (Slowing et al, 2008; Desai et al, 2018; Xu et al, 2018). Majority of chemotherapeutics and nutraceuticals with anticancer potential are hydrophobic in nature and as is the case of MSNs have been frequently used to demonstrate delivery of such substances.…”

Nanobiofunctionalized chitosan nanocomposite hydrogel as a highly biocompatible cancer drug carrier

“…[ 42 ] However, an increased hydrophobicity of the overall drug carrier system, with a higher amount of hydrophobic drug in the carrier, would lead to a decreased or delayed release of drugs as a result of irreversible drug carrier interaction. [ 43 ]…”