Nano MOF Entrapping Hydrophobic Photosensitizer for Dual-Stimuli-Responsive Unprecedented Therapeutic Action against Drug-Resistant Bacteria

authored by: Damayanti Bagchi, Anindita Bhattacharya, Tanushree Dutta, Sudip Nag, Dirk Wulferding, Peter Lemmens, Samir Kumar Pal
Abstract: Multidrug resistance (MDR) of bacteria is a major threat to public health globally and its unprecedented increase calls for immediate alternative medical strategies. Antimicrobial photodynamic therapy (aPDT) offers alternative modalities to combat the growing MDR typically by means of targeted cellular internalization of a photosensitizer (PS) capable of producing photoinduced reactive oxygen species (ROS). However, aPDT is severely limited by the self-aggregation behavior and hydrophobicity of PS molecules, which significantly curbs its viability for clinical application. The present study reports the use of modified nanoscale metal-organic frameworks (NMOFs) encapsulating a hydrophobic PS drug squaraine (SQ) to enhance aPDT efficacy against drug-resistant planktonic bacteria and its biofilm for the first time. Zeolitic imidazolate framework (ZIF-8) NMOF nanocrystals are attached postsynthetically with SQ (designated as ZIF8-SQ) and the resultant drug-doped NMOF is characterized by TEM, FESEM, PXRD, Raman spectroscopy, UV-vis spectroscopy, and steady-state and time-resolved fluorescence techniques. The microporous structures of ZIF-8 behave as molecular cages ceasing the self-aggregation of hydrophobic SQ. In addition, the formulated ZIF8-SQ produces cytotoxic ROS under red-light irradiation (650 nm) in a pH sensitive way primarily due to molecular level interaction and charge separation between ZIF-8 and SQ depicting a dual-stimuli-responsive nature. Most notably, ZIF8-SQ provides unparalleled aPDT action against methicillin-resistant Staphylococcus aureus (MRSA) and leads to complete loss of adherence of structurally robust bacterial biofilms. Finally, the nontoxic nature of the nanoconjugate toward human cells holds great promise for effective treatment of MRSA and other detrimental antibiotic-resistant microbes in clinical models.
External Organisation(s): S N Bose National Centre for Basic Science
St. Xavier's College, Kolkata
University of Calcutta
Technische Universität Braunschweig
Type: Article
Journal: ACS Applied Bio Materials
Volume: 2
Pages: 1772-1780
No. of pages: 9
Publication date: 15.04.2019
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Chemistry(all), Biomaterials, Biomedical Engineering, Biochemistry, medical
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): https://doi.org/10.1021/acsabm.9b00223 (Access: Closed)

BibTeX

@article{3853c22817a54c509dff98eaccafd592,
title = "Nano MOF Entrapping Hydrophobic Photosensitizer for Dual-Stimuli-Responsive Unprecedented Therapeutic Action against Drug-Resistant Bacteria",
abstract = "Multidrug resistance (MDR) of bacteria is a major threat to public health globally and its unprecedented increase calls for immediate alternative medical strategies. Antimicrobial photodynamic therapy (aPDT) offers alternative modalities to combat the growing MDR typically by means of targeted cellular internalization of a photosensitizer (PS) capable of producing photoinduced reactive oxygen species (ROS). However, aPDT is severely limited by the self-aggregation behavior and hydrophobicity of PS molecules, which significantly curbs its viability for clinical application. The present study reports the use of modified nanoscale metal-organic frameworks (NMOFs) encapsulating a hydrophobic PS drug squaraine (SQ) to enhance aPDT efficacy against drug-resistant planktonic bacteria and its biofilm for the first time. Zeolitic imidazolate framework (ZIF-8) NMOF nanocrystals are attached postsynthetically with SQ (designated as ZIF8-SQ) and the resultant drug-doped NMOF is characterized by TEM, FESEM, PXRD, Raman spectroscopy, UV-vis spectroscopy, and steady-state and time-resolved fluorescence techniques. The microporous structures of ZIF-8 behave as molecular cages ceasing the self-aggregation of hydrophobic SQ. In addition, the formulated ZIF8-SQ produces cytotoxic ROS under red-light irradiation (650 nm) in a pH sensitive way primarily due to molecular level interaction and charge separation between ZIF-8 and SQ depicting a dual-stimuli-responsive nature. Most notably, ZIF8-SQ provides unparalleled aPDT action against methicillin-resistant Staphylococcus aureus (MRSA) and leads to complete loss of adherence of structurally robust bacterial biofilms. Finally, the nontoxic nature of the nanoconjugate toward human cells holds great promise for effective treatment of MRSA and other detrimental antibiotic-resistant microbes in clinical models.",
keywords = "antibiofilm effect, antimicrobial action, multidrug-resistant bacteria, nanoscale metal-organic framework (NMOF), photodynamic therapy (PDT), squaraine (SQ), stimuli responsive",
author = "Damayanti Bagchi and Anindita Bhattacharya and Tanushree Dutta and Sudip Nag and Dirk Wulferding and Peter Lemmens and Pal, {Samir Kumar}",
note = "Funding Information: D.B. thanks the Department of Science and Technology (DST, India) for INSPIRE fellowship. T.D. thanks DST, India for NPDF fellowship (PDF/2017/002448). We thank Mr. Soumendra Singh for helping us to check the similarity index of the manuscript. We thank DST-SERB EMR/2016/004698 and DBT-BT/PR11534/NNT/28/766/2014 for financial support. D.W. and P.L. acknowledge support from {"}Niedersa?chsisches Vorab{"} through QUANOMET NL-4, NANOMET (DFG-RTG 1952), and the excellence cluster QuantumFrontiers.",
year = "2019",
month = apr,
day = "15",
doi = "10.1021/acsabm.9b00223",
language = "English",
volume = "2",
pages = "1772--1780",
journal = "ACS Applied Bio Materials",
issn = "2576-6422",
publisher = "American Chemical Society",
number = "4",
}