We have been able to create a toolbox based on MSNs with many available tools to adapt this nanoplatform to the individual needs of every patient and disease. Thus, and considering that the General Objective of the VERDI project was Developing a versatile polyvalent system that could be adapted to situations of clinical relevance, we have been able to go a step further in comparison with the previous period, producing the versatile polyvalent system and exploring it as a potential treatment to three different diseases.
Concerning INFECTION treatment, the great versatility of MSNs has allowed us to advance in developing different nanosystems to treat bacterial infection able to overcome the limitations of current treatments. To this aim, five approaches have been addressed, mainly focused in achieving: (i) Deep knowledge on antibiotic released doses from MSNs and their impact on Gram+ and Gram- bacterial biofilms, a pivotal study for future custom-made therapies; (ii) Targeted therapy (to bacterial wall and/or biofilm); (iii) Furtive antibacterial nanosystems able to evade the immune system defence mechanisms; (iv) Combined antimicrobial therapies for improved and/or synergistic antibacterial and/or antibiofilm effects, such as the combination of different antibiotics with different but complementary activity, or antibiotics and antimicrobial metal ions, into a single mesoporous silica carrier; (v) Stimuli-response antibiotic delivery therapies through near infrared light and magnetic external stimulus.
Concerning CANCER treatment, significant achievements were made in developing advanced MSNs-based nanosystems for bone cancer therapy. Different approaches have been conducted, focused on achieving: i) Selectivity towards tumor vascular endothelium or tumor cell membrane of solid tumors, by decorating drug-loaded MSNs with active targeting elements; ii) Zero premature chemotherapeutic cargo release until the target is reached, by developing stimuli-responsive nanosystems that release the drug within the tumor cell once exposed to certain stimuli (pH, redox conditions, magnetic field, light, etc); iii) Deep penetration into dense tumoral masses by using non-pathogenic bacteria as carriers of drug-loaded MSNs, or either anchoring proteolytic enzymes on the MSNs surface to digest the collagen-rich and dense extracellular matrix.
Concerning OSTEOPOROSIS, we have been able to co-deliver two therapeutic agents – SOST siRNA and osteostatin – inside cells using MSNs as nanocarriers. The employed siRNA was selected to silence SOST, which is responsible for the expression of sclerostin, overexpression of which reduces osteoblast formation and differentiation. Thus, silencing SOST with a specific siRNA in osteocytes could represent an effective alternative treatment approach. Additionally, the network of cavities from MSNs allowed loading an osteogenic peptide, osteostatin – a parathyroid hormone–related peptide that has been observed to stimulate osteoblastic cell growth and differentiation. Thanks to the VERDI project, the developed platform was evaluated both in vitro and in vivo, observing that the combination of SOST siRNA with the osteogenic peptide in ovariectomized mice resulted in a synergy – not only knocking down the selected gene, but also increasing the expression of early markers of osteogenic differentiation, and improving the bone microarchitecture.
