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submitted on 28.09.2020 and posted on 29.09.2020by Ana V. Morales-de-Echegaray, Lu Lin, badhu Sivasubramaniam, Aiganym Yermembetova, qi wang, Nader S. Abutaleb, Mohamed N. Seleem, Alexander Wei
We have developed a nanosized agent for targeted antimicrobial photodynamic therapy
(aPDT), comprised of GaPpIX (a hemin analog with potent photosensitizer
activity) encapsulated in haemoglobin (GaHb), mounted on 10-nm Ag nanoparticles
(AgNPs). The average GaHb–AgNP contains 28 GaPpIX units stabilized by Hb αβ-dimer units. Eradication (>6-log reduction)
of S. aureus and MRSA can be achieved
by a 10-second exposure to 405-nm irradiation from a light-emitting diode (LED)
array (140 mW/cm2), with GaHb–AgNP loadings as low as 5.6 μg/mL for S.
aureus and 16.6 μg/mL
for MRSA, corresponding to nanomolar levels of GaPpIX. This reduction in
bacterial count is several orders of magnitude greater than that of GaHb or
free GaPpIX on a per mole basis. The
GaHb-AgNP platform is also effective against persister MRSA and intracellular
MRSA, and can provide comparable levels of aPDT with a 15-minute irradiation by
an inexpensive compact fluorescent lightbulb. Collateral phototoxicity to
keratinocytes (HaCaT cells) is low at the GaHb–AgNP concentrations and fluences
used for aPDT. GaHb adsorbed on 10-nm AgNPs are much more potent than those on
40-nm AgNPs or 10-nm AuNPs, indicating that both size and plasmon-resonant
coupling are important factors for enhanced aPDT.