Regulation
of wound pH from alkaline to acidic is a simple and powerful approach
to reduce wound microbial colonization and infection. Here, we present
a nanocomposite material possessing intrinsic acidic surface pH as
an innovative antimicrobial wound dressing. This material comprises
an agarose matrix nanocomposite containing nanoparticles (NPs) of
the cesium salt of phosphotungstic heteropolyacid (Cs2.5H0.5PW12O40). Self-supporting films
were prepared by a casting method incorporating 5–20 wt % Cs2.5H0.5PW12O40 NPs into the
matrix. Films are flexible with tensile strengths between 28.55 and
32.15 MPa and exhibit broad biocidal activity against neutralophilic
pathogens, including Gram-positive bacteria, Gram-negative bacteria,
yeast, and filamentous fungi. The nano-antimicrobial Cs2.5H0.5PW12O40 functions as an efficient
and self-controlled proton delivery agent that lowers the surface
pH of the nanocomposites to the range 7.0 > pH ≥ 3.0. Nanocomposite
films containing 20 wt % Cs2.5H0.5PW12O40 NPs presented a surface pH of 3.0 and highest antimicrobial
activity. Using quantitative reverse transcription polymerase chain
reaction, we demonstrated that the antimicrobial mechanism of the
nanocomposites is acid-induced because of the transcriptional induction
of glutamate-dependent acid resistance genes in Escherichia
coli. Additionally, nanocomposite films do not damage
skin according to an in vivo rabbit skin model with no derived edema
or erythema. The wound care safety of this material is due to low
release of heavy metal heteropolyanions ([PW12O40]3–), no nanoparticle leaching, and proton controlled
release resulting in nonirritating acid levels for human skin models.