TY - JOUR

T1 - Cooperative Functionalities in Porous Nanoparticles for Seeking Extracellular DNA and Targeting Pathogenic Biofilms via Photodynamic Therapy

AU - Bronner, Hannah

AU - Brunswig, Fabian

AU - Pluta, Denis

AU - Krysiak, Yaşar

AU - Bigall, Nadja

AU - Plettenburg, Oliver

AU - Polarz, Sebastian

N1 - Funding Information: Part of this work was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) with the grant agreement BI 1708/4-1 and under Germany’s excellence strategy within the cluster of excellence PhoenixD (EXC 2122, project ID 390833453).

PY - 2023/3/22

Y1 - 2023/3/22

N2 - Many pathogenic bacteria are getting more and more resistant against antibiotic treatment and even become up to 1.000× times more resilient in the form of a mature biofilm. Thus, one is currently prospecting for alternative methods for treating microbial infections, and photodynamic therapy is a highly promising approach by creating so-called reactive oxygen species (ROS) produced by a photosensitizer (PS) upon irradiation with light. Unfortunately, the unspecific activity of ROS is also problematic as they are harmful to healthy tissue as well. Notably, one knows that uncontrolled existence of ROS in the body plays a major role in the development of cancer. These arguments create need for advanced theranostic materials which are capable of autonomous targeting and detecting the existence of a biofilm, followed by specific activation to combat the infection. The focus of this contribution is on mesoporous organosilica colloids functionalized by orthogonal and localized click-chemistry methods. The external zone of the particles is modified by a dye of the Hoechst family. The particles readily enter a mature biofilm where adduct formation with extracellular DNA and a resulting change in the fluorescence signal occurs, but they cannot cross cellular membranes such as in healthy tissue. A different dye suitable for photochemical ROS generation, Acridine Orange, is covalently linked to the surfaces of the internal mesopores. The spectral overlap between the emission of Hoechst with the absorption band of Acridine Orange facilitates energy transfer by Förster resonance with up to 88% efficiency. The theranostic properties of the materials including viability studies were investigated in vitro on mature biofilms formed by Pseudomonas fluorescens and prove the high efficacy.

AB - Many pathogenic bacteria are getting more and more resistant against antibiotic treatment and even become up to 1.000× times more resilient in the form of a mature biofilm. Thus, one is currently prospecting for alternative methods for treating microbial infections, and photodynamic therapy is a highly promising approach by creating so-called reactive oxygen species (ROS) produced by a photosensitizer (PS) upon irradiation with light. Unfortunately, the unspecific activity of ROS is also problematic as they are harmful to healthy tissue as well. Notably, one knows that uncontrolled existence of ROS in the body plays a major role in the development of cancer. These arguments create need for advanced theranostic materials which are capable of autonomous targeting and detecting the existence of a biofilm, followed by specific activation to combat the infection. The focus of this contribution is on mesoporous organosilica colloids functionalized by orthogonal and localized click-chemistry methods. The external zone of the particles is modified by a dye of the Hoechst family. The particles readily enter a mature biofilm where adduct formation with extracellular DNA and a resulting change in the fluorescence signal occurs, but they cannot cross cellular membranes such as in healthy tissue. A different dye suitable for photochemical ROS generation, Acridine Orange, is covalently linked to the surfaces of the internal mesopores. The spectral overlap between the emission of Hoechst with the absorption band of Acridine Orange facilitates energy transfer by Förster resonance with up to 88% efficiency. The theranostic properties of the materials including viability studies were investigated in vitro on mature biofilms formed by Pseudomonas fluorescens and prove the high efficacy.

KW - antibacterial photodynamic therapy

KW - biofilm disruption

KW - click chemistry

KW - DNA-binding properties

KW - Förster resonance energy transfer (FRET)

KW - multifunctional materials

KW - porous organosilica nanoparticles

UR - http://www.scopus.com/inward/record.url?scp=85149724821&partnerID=8YFLogxK

U2 - 10.1021/acsami.3c00210

DO - 10.1021/acsami.3c00210

M3 - Article

AN - SCOPUS:85149724821

VL - 15

JO - ACS Applied Materials and Interfaces

JF - ACS Applied Materials and Interfaces

SN - 1944-8244

IS - 11

ER -