A nano phototheranostic approach of toluidine blue conjugated gold silver core shells mediated photodynamic therapy to treat diabetic foot ulcer

Farheen Akhtar,Asad U Khan,Bushra Qazi,Asif Ali,Kafil Akhtar,Prashant Mishra,Senthilguru Kulanthaivel

doi:10.1038/s41598-021-04008-x

Abstract

Diabetic foot infection caused by multidrug-resistant bacteria, is becoming serious problem. Moreover, polymicrobial biofilms contribute significantly to the persistent infections. In the present study, we investigated the effectiveness of novel toluidine blue conjugated chitosan coated gold–silver core–shell nanoparticles (TBO–chit–Au–AgNPs) mediated photodynamic therapy and demonstrate their use as a nontoxic antibacterial therapy to combat diabetic foot ulcer (DFU) caused by multi-drug resistant strains both in monomicrobial and polymicrobial state of infection. In vitro efficacy of TBO–chit–Au–AgNPs mediated photodynamic therapy (PDT) against polymicrobial biofilms was determined using standard plate count method and compared with that of monomicrobial biofilms of each species. Different anti-biofilm assays and microscopic studies were performed to check the efficacy of TBO–chit–Au–AgNPs mediated PDT, displayed significant decrease in the formation of biofilm. Finally, its therapeutic potential was validated in vivo type-2DFU. Cytokines level was found reduced, using nano-phototheranostic approach, indicating infection control. Expression profile of growth factors confirmed both the pathogenesis and healing of DFU. Hence, we conclude that TBO–chit–Au–AgNPs mediated PDT is a promising anti-bacterial therapeutic approach which leads to a synergistic healing of DFU caused by MDR bacterial strains.

Highlights

Diabetic foot infection caused by multidrug-resistant bacteria, is becoming serious problem
It has been reported that up to one-third of people with diabetes may develop foot ulcer during their lifetime and over 50% of these ulcers become infected. This challenge is further aggravated by the emergence of multidrug-resistance (MDR) strains induced diabetic foot infections (DFIs) which leads to increasing morbidity and mortality, and risk of lower extremity amputation (LEA) which causes low quality of life[3,4,5,6]
The result of zeta potential clearly illustrates chit–Au–AgNPs synthesized through stepwise addition of AgNO3 retains their positive zeta potential of +37.6 mV, which shows that the polymeric coating is well-preserved all through the formation of core–shell nanoparticles

Summary

Introduction

Diabetic foot infection caused by multidrug-resistant bacteria, is becoming serious problem. We investigated the effectiveness of novel toluidine blue conjugated chitosan coated gold–silver core–shell nanoparticles (TBO–chit–Au–AgNPs) mediated photodynamic therapy and demonstrate their use as a nontoxic antibacterial therapy to combat diabetic foot ulcer (DFU) caused by multi-drug resistant strains both in monomicrobial and polymicrobial state of infection. PDT combines the action of light on a nontoxic photosensitizer (PS) which causes production of reactive oxygen species being toxic to cellular components This approach is highly effective in killing MDR strains since microorganisms do not acquire resistance toward PDT49.The use of TBO–chit–Au–AgNPs mediated PDT has not been reported yet. We initiated this study to provide a novel approach toward potential applications of nano-phototheranostic complex, as a nontoxic antibacterial agent to combat DFU caused by multi-drug resistant bacterial strains (Fig. 1)

Methods

Results

Discussion

Conclusion