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

Abstract

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.

Development of New Targeted Nanotherapy Combined with Magneto-Fluorescent Nanoparticles against Colorectal Cancer

“…As demonstrated in a previous work of our group [ 34 ], the synthesis of NANO3-SH resulted in well-defined spherical, single core–shell particles with an average diameter of 60 nm and a shell porous matrix with pores of ca. 2.5–3.0 nm.…”

“…The empty porous matrix of NANO3 was used to load both a model anticancer and an antibiotic, in single and dual formulations, to exploit existent synergetic effects between them such as improved therapeutic activity and release parameters, as previously demonstrated by our group [ 34 ]. The loading of both drugs was performed in an intermediate step of NANO3-SH synthesis, via electrostatic interactions with non-templated NANO2-COOH, before pores capping with SiQDs and thiolated species.…”

“…CTX-SH and AZM-SH disulphide bridges with NANO3-SH systems are mostly broken in such conditions, with NANO3@drug–SH systems being representative of the release interface during its therapeutic action, either inside or outside CRC cells. The simulation of cancer microenvironment and its role in drug delivery from NANO3@drug–SH nanosystems was achieved by studying drug release in both physiological (pH 7.4) and acidic (pH 5.0) conditions ( Figure 5 a,b) for 72 h. When compared with the results obtained in previous studies [ 34 ] for non-thiolated NANO3 systems, under the same conditions, one concludes that although the final functionalization with thiol moieties does not change the release tendencies for different pHs, it changes the total released quantities of drugs. This effect is particularly significant for total released OFLO from both NANO3@O-SH and NANO3@DO-SH, which see, respectively, a 10-fold and 3-fold reduction when compared to their non-thiolated counterparts.…”

“…NANO3 nanoparticles previously synthesized in [ 34 ] were obtained using EDC/NHS cross-linkage of NANO2-COOH with the NH 2 groups of the synthesized SiQDs, in a SiQD excess to avoid inter-NANO3 cross-linkage. The same strategy was used to thiolate NANO3 surface NH 2 groups with thioglycolic acid (TGA), producing NANO3-SH (see Scheme 2 ).…”

“…Considering this, herein we report the synthesis of a novel AZM-derivative containing a sulfhydryl anchoring moiety, and its subsequent biofunctionalization on superparamagnetic, fluorescent iron oxide-cored mesoporous silica nanoparticles (NANO3-SH). This system was successfully evaluated as a potential anticancer tool against CRC cell lines [ 34 ]. The development of a dual anti-EGFR/anti-hCA IX (CTX+AZM) targeting nanoprobe is also reported, and its performance as a precision therapeutic tool against CRC is compared with that of each individual NANO3-anchored antigen.…”