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 <i>S. aureus</i> and MRSA can be achieved by a 10-second exposure to 405-nm irradiation from a light-emitting diode (LED) array (140

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... p>2</sup>), with GaHb–AgNP loadings as low as 5.6 μg/mL for <i>S. aureus</i> 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.<br>