Multifunctional Nanoplatforms for Targeted Multidrug-Resistant-Bacteria Theranostic Applications

Abstract

The emergence of multidrug-resistant-bacteria (MDRB) infection poses a major burden to modern healthcare. Early detection in the bloodstream and a new strategy development for MDRB infection treatment without antibiotics are clinically significant to save millions of lives every year. To tackle the MDRB challenge, the current manuscript reports the design of "multifunctional nanoplatforms" consisting of a magnetic core-plasmonic shell nanoparticle, a methylene blue-bound aptamer, and an MDRB Salmonella DT104 specific antibody. The reported "multifunctional nanoplatform" is capable of targeted separation from a blood sample and sensing and multimodal therapeutic killing of MDRB. Experimental data using an MDRB-infected whole-blood sample show that nanoplatforms can be used for selective magnetic separation and fluorescence imaging. In vitro light-triggered photodestruction of MDRB, using combined photodynamic and photothermal treatment, shows that the multimodal treatment regime can enhance MDRB killing significantly. We discussed the possible mechanisms on combined synergistic therapy for killing MDRB. The "multifunctional nanoplatform" reported in this manuscript has great potential for the imaging and combined therapy of MDRB in clinical settings.

Multifunctional Au nanoclusters for targeted bioimaging and enhanced photodynamic inactivation of Staphylococcus aureus

“…[29][30][31] The main challenge in treating MRD pathogens comes from the continual emergence of new MRD strains with a parallel significant decline in new market-available antibiotics. 31,32 This situation clearly points to the urgent need to develop new, nonantibiotic strategies for curing MRD infections. Another challenge is associated with the sensitive, early detection of MRD pathogens, as the standard culturing methods are timeconsuming, tedious, and impractical for real-time applications.…”

“…Another challenge is associated with the sensitive, early detection of MRD pathogens, as the standard culturing methods are timeconsuming, tedious, and impractical for real-time applications. 32 Both challenges can be resolved with the use of multifunctional theranostic nanocomposites that combine therapeutic, diagnostic, and sensing modalities in a single nanostructure. [33][34][35][36][37] In this regard, protein-or glutathione-organs of the reticuloendothelial system are the primary targets of accumulating Au nanoparticles with sizes ranging from 5 to 100 nm.…”

“…It should also be emphasized that targeting at acidic pH<5−6 cannot be used for in vivo applications, e.g., for the early detection of pathogenic bacteria in the bloodstream. 32 Thus, to the best of our knowledge, there have been no reports on the application of multifunctional fluorescent Au NCs to selective detection and PD inactivation of pathogenic bacteria. Here, we describe Au-BSA NCs functionalized with targeting molecules (human antistaphylococcal immunoglobulin, antiSAIgG) and the PD dye Photosens TM (PS) 53 for selective detection and effective PD inactivation of both MSSA and MRSA.…”

Gold nanoparticle labeling based ICP-MS detection/measurement of bacteria, and their quantitative photothermal destruction

“…45–48 In addition, plasmatic gold nanotechnology has the potential to be a solution for treating multi-drug resistant bacteria (MDRB) infection and cancer, with high biocompatibility. 49 Various methods have been applied to attach antibodies to gold nanoparticles whereby selective binding with bacteria occurs through a specific antibody-antigen interaction. These methods include: 1) Linking the antibody to GNPOP directly, which takes advantage of the predominant glycosylation of the fragment crystallizable region of the antibody; 2) Linking the antibody to GNPOP by Cysteamine, which is known as the "glutaraldehyde spacer method"; 3) Linking the antibody to GNPOP by electrostatic interaction; and 4) Linking the antibody to GNPOP by Carboxy-PEG12-Thiol (PEG-SH).…”

Magnetically Encoded Luminescent Composite Nanoparticles through Layer‐by‐Layer Self‐Assembly

“…QDs are of particular interest due to their excellent photostability, high quantum yield, narrow emission peaks, and size-dependent tunable emission wavelength. [11][12][13] As the magnetic component, iron oxide magnetic nanoparticles (MNPs), especially magnetite (Fe 3 O 4 ), and maghemite (Fe 2 O 3 ), have been most often used to fabricate FMMNPs [14][15][16] because of their room-temperature superparamagnetism, chemical stability, and biocompatibility. [17,18] To date, several methods have been developed to design FMMNPs based on QDs and iron oxide MNPs.…”