Details
Original language | English |
---|---|
Pages (from-to) | 1772-1780 |
Number of pages | 9 |
Journal | ACS Applied Bio Materials |
Volume | 2 |
Issue number | 4 |
Early online date | 26 Mar 2019 |
Publication status | Published - 15 Apr 2019 |
Externally published | Yes |
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
ASJC Scopus subject areas
- Chemistry(all)
- General Chemistry
- Materials Science(all)
- Biomaterials
- Engineering(all)
- Biomedical Engineering
- Medicine(all)
- Biochemistry, medical
Sustainable Development Goals
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In: ACS Applied Bio Materials, Vol. 2, No. 4, 15.04.2019, p. 1772-1780.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Nano MOF Entrapping Hydrophobic Photosensitizer for Dual-Stimuli-Responsive Unprecedented Therapeutic Action against Drug-Resistant Bacteria
AU - Bagchi, Damayanti
AU - Bhattacharya, Anindita
AU - Dutta, Tanushree
AU - Nag, Sudip
AU - Wulferding, Dirk
AU - Lemmens, Peter
AU - Pal, Samir Kumar
N1 - 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.
PY - 2019/4/15
Y1 - 2019/4/15
N2 - 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.
AB - 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.
KW - antibiofilm effect
KW - antimicrobial action
KW - multidrug-resistant bacteria
KW - nanoscale metal-organic framework (NMOF)
KW - photodynamic therapy (PDT)
KW - squaraine (SQ)
KW - stimuli responsive
UR - http://www.scopus.com/inward/record.url?scp=85070563253&partnerID=8YFLogxK
U2 - 10.1021/acsabm.9b00223
DO - 10.1021/acsabm.9b00223
M3 - Article
AN - SCOPUS:85070563253
VL - 2
SP - 1772
EP - 1780
JO - ACS Applied Bio Materials
JF - ACS Applied Bio Materials
IS - 4
ER -