Increased Toxicity of Doxorubicin Encapsulated into pH-Responsive Poly(β-Amino Ester)-Functionalized MCM-41 Silica Nanoparticles

Abstract

Background: The encapsulation of anti-cancer drugs in stimulus-sensitive release systems may provide advantages such as enhanced drug toxicity in tumour tissue cells due to increased intracellular drug release. Encapsulation may also improve release in targeted tissue due to the response to a stimulus such as pH, which is lower in the tumour tissue microenvironment. Here, we evaluated the in vitro toxicity of the Drug Doxorubicin (DOX) loaded into a release system based on poly(β-amino ester)- modified MCM-41 silica nanoparticles. Methods: The MCM-41-DOX-PbAE release system was obtained by loading DOX into MCM-41 nanoparticles amino-functionalized with 3-aminopropyltriethoxysilane (APTES) and then coated with a pH-responsive poly(β-amino ester) (PbAE). The physicochemical characteristics of the release system were evaluated through TEM, FTIR and TGA. Cytotoxicity assays were performed on the MCM-41- DOX-PbAE system to determine their effects on the inhibition of human MCF-7 breast cancer cell proliferation after 48 h of exposure through crystal violet assay; the investigated systems included MCF-7 cells with MCM-41, PbAE, and MCM-41-PbAE alone. Additionally, the release of DOX and the change in pH in vitro were determined. Results: The physicochemical characteristics of the synthesized MCM-41-PbAE system were confirmed, including the nanoparticle size, spherical morphology, mesoporous ordered structure, and presence of PbAE on the surface of the MCM-41 nanoparticles. Likewise, we demonstrated that the release of DOX from the MCM-41-DOX-PbAE system promoted an important reduction in MCF-7 cell viability (~ 70%) compared to the values obtained with MCM-41, PbAE, and MCM-41-PbAE, as well as a reduction in the viability under treatment with just DOX (~ 50%). Conclusions: The results suggest that all the components of the release system are biocompatible and that the encapsulation of DOX in MCM-41-PbAE could allow better intracellular release, which would probably increase the availability and toxic effect of DOX.