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Gold Nanoparticle-Photosensitizer Conjugate Based Photodynamic Inactivation of Biofilm Producing Cells: Potential for Treatment of C. albicans Infection in BALB/c Mice.

Sherwani MA, Tufail S, Khan AA, Owais M - PLoS ONE (2015)

Bottom Line: Photodynamic therapy (PDT) has been found to be effective in inhibiting biofilm producing organisms.We investigated the photodynamic effect of gold nanoparticle (GNP) conjugated photosensitizers against Candida albicans biofilm.The GNP-PS conjugate based PDT was found to effectively kill both C. albicans planktonic cells and biofilm populating hyphal forms.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.

ABSTRACT

Background: Photodynamic therapy (PDT) has been found to be effective in inhibiting biofilm producing organisms. We investigated the photodynamic effect of gold nanoparticle (GNP) conjugated photosensitizers against Candida albicans biofilm. We also examined the photodynamic efficacy of photosensitizer (PS) conjugated GNPs (GNP-PS) to treat skin and oral C. albicans infection in BALB/c mice.

Methods: The biomimetically synthesized GNPs were conjugated to photosensitizers viz. methylene blue (MB) or toluidine blue O (TB). The conjugation of PSs with GNPs was characterized by spectroscopic and microscopic techniques. The efficacy of gold nanoparticle conjugates against C. albicans biofilm was demonstrated by XTT assay and microscopic studies. The therapeutic efficacy of the combination of the GNP conjugates against cutaneous C. albicans infection was examined in mouse model by enumerating residual fungal burden and histopathological studies.

Results: The GNP-PS conjugate based PDT was found to effectively kill both C. albicans planktonic cells and biofilm populating hyphal forms. The mixture of GNPs conjugated to two different PSs significantly depleted the hyphal C. albicans burden against superficial skin and oral C. albicans infection in mice.

Conclusion: The GNP-PS conjugate combination exhibits synergism in photodynamic inactivation of C. albicans. The GNP conjugate based PDT can be employed effectively in treatment of cutaneous C. albicans infections in model animals. The antibiofilm potential of PDT therapy can also be exploited in depletion of C. albicans on medical appliances such as implants and catheters etc.

No MeSH data available.


Related in: MedlinePlus

Uptake of GNP-PS conjugates by activated macrophages.(A) Macrophages exposed to MB (B) TB treated macrophages (C) GNP-MB conjugate entrapped by macrophages (D) GNP-TB complex engulfed by macrophages (E) Macrophages are seen with GNP-MB and GNP-TB entrapped within. Upper panel shows fluorescent images and lower panel exhibits the corresponding brightfield images.
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pone.0131684.g006: Uptake of GNP-PS conjugates by activated macrophages.(A) Macrophages exposed to MB (B) TB treated macrophages (C) GNP-MB conjugate entrapped by macrophages (D) GNP-TB complex engulfed by macrophages (E) Macrophages are seen with GNP-MB and GNP-TB entrapped within. Upper panel shows fluorescent images and lower panel exhibits the corresponding brightfield images.

Mentions: Since yeast form of C. albicans can intrude the macrophages [30], it can be speculated that uptake of GNP-PS conjugates by macrophages would render close proximity of PS with intracellular C. albicans. Upon subsequent light exposure, free radicals generated by PSs would readily act upon the C. albicans cells present in the vicinity ensuing in effective killing of the pathogens. Consequently, we investigated the cellular uptake of GNP-PS complex in macrophages isolated from the peritoneal cavity of thioglycolate primed BALB/c mice. The isolated macrophages were incubated with PS conjugated GNPs. Endocytosis of the GNP-PS complexes by the macrophages appears in the form of punctate fluorescence (Fig 6). The punctuate fluorescence intensity in the macrophages incubated with the mixture of GNP-MB and GNP-TB is significantly higher when compared to that incubated with either of the conjugates alone. The macrophages exhibited very feeble punctuate fluorescence for the unconjugated MB and TB possibly because of their non-particulate nature (Fig 6).


Gold Nanoparticle-Photosensitizer Conjugate Based Photodynamic Inactivation of Biofilm Producing Cells: Potential for Treatment of C. albicans Infection in BALB/c Mice.

Sherwani MA, Tufail S, Khan AA, Owais M - PLoS ONE (2015)

Uptake of GNP-PS conjugates by activated macrophages.(A) Macrophages exposed to MB (B) TB treated macrophages (C) GNP-MB conjugate entrapped by macrophages (D) GNP-TB complex engulfed by macrophages (E) Macrophages are seen with GNP-MB and GNP-TB entrapped within. Upper panel shows fluorescent images and lower panel exhibits the corresponding brightfield images.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4493101&req=5

pone.0131684.g006: Uptake of GNP-PS conjugates by activated macrophages.(A) Macrophages exposed to MB (B) TB treated macrophages (C) GNP-MB conjugate entrapped by macrophages (D) GNP-TB complex engulfed by macrophages (E) Macrophages are seen with GNP-MB and GNP-TB entrapped within. Upper panel shows fluorescent images and lower panel exhibits the corresponding brightfield images.
Mentions: Since yeast form of C. albicans can intrude the macrophages [30], it can be speculated that uptake of GNP-PS conjugates by macrophages would render close proximity of PS with intracellular C. albicans. Upon subsequent light exposure, free radicals generated by PSs would readily act upon the C. albicans cells present in the vicinity ensuing in effective killing of the pathogens. Consequently, we investigated the cellular uptake of GNP-PS complex in macrophages isolated from the peritoneal cavity of thioglycolate primed BALB/c mice. The isolated macrophages were incubated with PS conjugated GNPs. Endocytosis of the GNP-PS complexes by the macrophages appears in the form of punctate fluorescence (Fig 6). The punctuate fluorescence intensity in the macrophages incubated with the mixture of GNP-MB and GNP-TB is significantly higher when compared to that incubated with either of the conjugates alone. The macrophages exhibited very feeble punctuate fluorescence for the unconjugated MB and TB possibly because of their non-particulate nature (Fig 6).

Bottom Line: Photodynamic therapy (PDT) has been found to be effective in inhibiting biofilm producing organisms.We investigated the photodynamic effect of gold nanoparticle (GNP) conjugated photosensitizers against Candida albicans biofilm.The GNP-PS conjugate based PDT was found to effectively kill both C. albicans planktonic cells and biofilm populating hyphal forms.

View Article: PubMed Central - PubMed

Affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.

ABSTRACT

Background: Photodynamic therapy (PDT) has been found to be effective in inhibiting biofilm producing organisms. We investigated the photodynamic effect of gold nanoparticle (GNP) conjugated photosensitizers against Candida albicans biofilm. We also examined the photodynamic efficacy of photosensitizer (PS) conjugated GNPs (GNP-PS) to treat skin and oral C. albicans infection in BALB/c mice.

Methods: The biomimetically synthesized GNPs were conjugated to photosensitizers viz. methylene blue (MB) or toluidine blue O (TB). The conjugation of PSs with GNPs was characterized by spectroscopic and microscopic techniques. The efficacy of gold nanoparticle conjugates against C. albicans biofilm was demonstrated by XTT assay and microscopic studies. The therapeutic efficacy of the combination of the GNP conjugates against cutaneous C. albicans infection was examined in mouse model by enumerating residual fungal burden and histopathological studies.

Results: The GNP-PS conjugate based PDT was found to effectively kill both C. albicans planktonic cells and biofilm populating hyphal forms. The mixture of GNPs conjugated to two different PSs significantly depleted the hyphal C. albicans burden against superficial skin and oral C. albicans infection in mice.

Conclusion: The GNP-PS conjugate combination exhibits synergism in photodynamic inactivation of C. albicans. The GNP conjugate based PDT can be employed effectively in treatment of cutaneous C. albicans infections in model animals. The antibiofilm potential of PDT therapy can also be exploited in depletion of C. albicans on medical appliances such as implants and catheters etc.

No MeSH data available.


Related in: MedlinePlus