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

BACKGROUND The encapsulation of anti-cancer drugs in stimulus-sensitive release systems may provide ad- vantages 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 mi- croenvironment. 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 func- tionalized 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 as- says were performed to 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 na- noparticle size, spherical morphology, mesoporous ordered structure, and presence of PbAE on the MCM-41 nanoparticles surface. 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 compared to 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.