Title:Increased Toxicity of Doxorubicin Encapsulated into pH-Responsive Poly(β-Amino Ester)-Functionalized MCM-41 Silica Nanoparticles
VOLUME: 17 ISSUE: 9
Author(s):Alejandro Ávila-Ortega, Leydi Maribel Carrillo-Cocom*, Christofer Enmanuel Olán-Noverola, Geovanny I. Nic-Can, Alfredo Rafael Vilchis-Nestor and William Alejandro Talavera-Pech
Affiliation:Facultad de Ingeniería Quimica, Universidad Autonoma de Yucatan, Merida, Yucatan, Facultad de Ingeniería Quimica, Universidad Autonoma de Yucatan, Merida, Yucatan, Facultad de Ingeniería Quimica, Universidad Autonoma de Yucatan, Merida, Yucatan, CONACYT-Facultad de Ingenieria Quimica, Universidad Autonoma de Yucatan, Merida, Yucatan, Centro Conjunto de Investigacion en Quimica Sustentable, Universidad Autonoma del Estado de Mexico-Universidad Nacional Autonoma de Mexico, Toluca, Centro de Investigacion en Corrosion, Universidad Autonoma de Campeche, Campeche
Keywords:Cancer cells, cytotoxicity, doxorubicin, drug delivery, mesoporous silica nanoparticles, pH-sensitive.
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%).
Conclusion: 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.