In vivo magnetic enrichment, photoacoustic diagnosis, and photothermal purging of infected blood using multifunctional gold and magnetic nanoparticles.
Bacterial infections are a primary cause of morbidity and mortality worldwide. Bacteremia is a particular concern owing to the possibility of septic shock and the development of metastatic infections. Treatment of bacteremia is increasingly compromised by the emergence of antibiotic resistant strains, creating an urgent need for alternative therapy. Here, we introduce a method for in vivo photoacoustic (PA) detection and photothermal (PT) eradication of Staphylococcus aureus in tissue and blood. We show that this method could be applicable for label-free diagnosis and treatment of in the bloodstream using intrinsic near-infrared absorption of endogenous carotenoids with nonlinear PA and PT contrast enhancement. To improve sensitivity and specificity for detection of circulating bacteria cells (CBCs), two-color gold and multilayer magnetic nanoparticles with giant amplifications of PA and PT contrasts were functionalized with an antibody cocktail for molecular targeting of S. aureus surface-associated markers such as protein A and lipoprotein. With a murine model, the utility of this approach was demonstrated for ultrasensitive detection of CBCs with threshold sensitivity as low as 0.5 CBCs/mL, in vivo magnetic enrichment of CBCs, PT eradication of CBCs, and real-time monitoring of therapeutic efficacy by CBC counting. Our PA-PT nano-theranostic platform, which integrates in vivo multiplex targeting, magnetic enrichment, signal amplification, multicolor recognition, and feedback control, could be used as a biological tool to gain insights on dissemination pathways of CBCs, infection progression by bacteria re-seeding, and sepsis development and treatment, and could potentially be feasible in humans, especially using bypass schematic.
Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Ekaterina I
EI
Galanzha
Evgeny
E
Shashkov
Mustafa
M
Sarimollaoglu
Karen E
KE
Beenken
Alexei G
AG
Basnakian
Mark E
ME
Shirtliff
Jin-Woo
JW
Kim
Mark S
MS
Smeltzer
Vladimir P
VP
Zharov
D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D016470:Bacteremia / Q000175:diagnosis* / Q000382:microbiology / Q000628:therapy*; D002338:Carotenoids / Q000737:chemistry* / Q000378:metabolism; D003116:Color; D000529:Complementary Therapies; D006046:Gold / Q000737:chemistry; D006358:Hot Temperature; D006801:Humans; D007834:Lasers; D008027:Light; D008074:Lipoproteins / Q000737:chemistry / Q000276:immunology; D058185:Magnetite Nanoparticles / Q000008:administration & dosage*; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging; D061088:Photoacoustic Techniques; D055668:Photochemical Processes; D051381:Rats; D013203:Staphylococcal Infections / Q000175:diagnosis* / Q000382:microbiology / Q000628:therapy*; D013205:Staphylococcal Protein A / Q000737:chemistry / Q000276:immunology; D013211:Staphylococcus aureus / Q000254:growth & development / Q000528:radiation effects
D000906:Antibodies; D008074:Lipoproteins; D058185:Magnetite Nanoparticles; D013205:Staphylococcal Protein A; D002338:Carotenoids; D006046:Gold