Magneto-Fluorescent Mesoporous Nanocarriers for the Dual-Delivery of Ofloxacin and Doxorubicin to Tackle Opportunistic Bacterial Infections in Colorectal Cancer

Abstract

Funding Information: This work was funded by the Associate Laboratory for Green Chemistry—LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020) as well as the Scientific Society PROTEOMASS (Portugal) for funding support (General Funding Grant 2021). G.M thanks to FCT/MEC (Portugal) for his doctoral grant PD/BD/142865/2018. E.O thanks FCT/MEC (Portugal) for the individual contract, CEECIND/00648/2017. This work was also funded by FCT—Foundation for Science and Technology, I.P., through projects UIDB/04077/2020, UIDP/04077/2020, OrMagNa—PTDC/NAN-MAT/28785/2017, BioISI—UID/Multi/04046/2019, UIDB/04046/2020 and UIDP/04046/2020 Centre grants (BioISI) and NECL infrastructure. Publisher Copyright: © 2022 by the authors.Cancer-related opportunistic bacterial infections are one major barrier for successful clinical therapies, often correlated to the production of genotoxic factors and higher cancer incidence. Although dual anticancer and antimicrobial therapies are a growing therapeutic fashion, they still fall short when it comes to specific delivery and local action in in vivo systems. Nanoparticles are seen as potential therapeutic vectors, be it by means of their intrinsic antibacterial properties and effective delivery capacity, or by means of their repeatedly reported modulation and maneuverability. Herein we report on the production of a biocompatible, antimicrobial magneto-fluorescent nanosystem (NANO3) for the delivery of a dual doxorubicin–ofloxacin formulation against cancer-related bacterial infections. The drug delivery capacity, rendered by its mesoporous silica matrix, is confirmed by the high loading capacity and stimuli-driven release of both drugs, with preference for tumor-like acidic media. The pH-dependent emission of its surface fluorescent SiQDs, provides an insight into NANO3 surface behavior and pore availability, with the SiQDs working as pore gates. Hyperthermia induces heat generation to febrile temperatures, doubling drug release. NANO3-loaded systems demonstrate significant antimicrobial activity, specifically after the application of hyperthermia conditions. NANO3 structure and antimicrobial properties confirm their potential use in a future dual anticancer and antimicrobial therapeutical vector, due to their drug loading capacity and their surface availability for further modification with bioactive, targeting species.publishersversionpublishe