Doxorubicin-Functionalized Silica Nanoparticles Incorporated into a Thermoreversible Hydrogel and Intraperitoneally Administered Result in High Prostate Antitumor Activity and Reduced Cardiotoxicity of Doxorubicin

• Published in: ACS biomaterials science & engineering Vol. 2; no. 7; pp. 1190 - 1199
• Main Authors: Silveira, Camila P, Apolinário, Letícia M, Fávaro, Wagner J, Paula, Amauri J, Durán, Nelson
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 11-07-2016
• Subjects: mesoporous silica nanoparticles; prostate cancer; cardiotoxicity; hydrogel; poloxamer; doxorubicin; drug delivery; Pluronic F-127
• ISSN: 2373-9878; 2373-9878
• DOI: 10.1021/acsbiomaterials.6b00241

Described here is an anticancer material based on colloidal mesoporous silica nanoparticles (MSNs) functionalized with doxorubicin (DOX), and incorporated into Pluronic F127 hydrogels for prolonged release, with a potential therapeutic application for prostate cancer treatment. The MSNs have spherical morphology, size of about 60 nm, surface area of 970 cm2 g–1 and average pore width of 2.0 nm. A high colloidal stability for the MSNs in the physiological medium used for in vivo administration (NaCl 0.9% w/v) could be attained in the presence of PF127 (from 5 to 18 wt %), where depletion repulsion forces prevent MSN agglomeration. By conjugating DOX, MSN and PF127 (18 wt %) in NaCl 0.9%, the hybrid system has a gelation temperature of 21 °C, which allowed its in vivo administration in the liquid form and further in situ gelation, generating a drug depot system inside the animals after peritoneal injection. The systems were tested in rats with chemically induced prostate cancer and, after this treatment, histopathological analyses confirmed (i) a reduction in the frequency of aggressive tumors; (ii) that the antitumor effect was dependent on MSN concentration; and most importantly (iii) the reduction of DOX intrinsic cardiotoxicity, indicating that the MSNs play a cardioprotective effect.