Synthesis of a theranostic platform based on fibrous silica nanoparticles for the enhanced treatment of triple-negative breast cancer promoted by a combination of chemotherapeutic agents
A new series of theranostic silica materials based on fibrous silica particles acting as nanocarriers of two different cytotoxic agents, namely, chlorambucil and an organotin metallodrug have been prepared and structurally characterized. Besides the combined therapeutic activity, these platforms have been decorated with a targeting molecule (folic acid, to selectively target triple negative breast cancer) and a molecular imaging agent (Alexa Fluor 647, to enable their tracking both in vitro and in vivo). The in vitro behaviour of the multifunctional silica systems showed a synergistic activity of the two chemotherapeutic agents in the form of an enhanced cytotoxicity against MDA-MB-231 cells (triple negative breast cancer) as well as by a higher cell migration inhibition. Subsequently, the in vivo applicability of the siliceous nanotheranostics was successfully assessed by observing with in vivo optical imaging techniques a selective tumour accumulation (targeting ability), a marked inhibition of tumour growth paired to a marked antiangiogenic ability after 13 days of systemic administration, thus, confirming the enhanced theranostic activity. The systemic nanotoxicity was also evaluated by analyzing specific biochemical markers. The results showed a positive effect in form of reduced cytotoxicity when both chemotherapeutics are administered in combination thanks to the fibrous silica nanoparticles. Overall, our results confirm the promising applicability of these novel silica-based nanoplatforms as advanced drug-delivery systems for the synergistic theranosis of triple negative breast cancer.
We would like to thank the funding of the Ministerio de Ciencia e Innovación of Spain (former Ministerio de Ciencia Innovación y Universidades of Spain) and FEDER, Una manera de hacer Europa for the grant number RTI2018-094322-B-I00. We would also like to thank Comunidad de Madrid for the predoctoral grant PEJD-2017-PRE/BMD-3512 (I.M.-P.). M.M, Y.L.M., and M.F. are grateful to the Comunidad Autónoma de Madrid and FEDER for the I + D collaborative Programme in Biomedicine NIETO-CM (Project reference B2017-BMD3731). M.F. and K.O.P. thank the Comunidad Autónoma de Madrid for research project No. 2017-T1/BIO-4992 (“Atracción de Talento” Action) cofunded by Universidad Complutense de Madrid. M.F is grateful to Instituto de Salud Carlos III (ISCIII) for project No DTS20/00109 (AES-ISCIII). M.M., M.F. and L.L.C would also like to thank Comunidad de Madrid for the predoctoral grant IND2020/BIO-17523. M.F. and K.O.P. acknowledge the support of Microscopy & Dynamic Imaging Unit of CNIC, Madrid, Spain. The Unit is part of the ReDiB-ICTS and has the support of FEDER, “Una manera de hacer Europa.” The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033)
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