Efficacy of Antimicrobial Photodynamic Therapy Mediated by Photosensitizers Conjugated with Inorganic Nanoparticles: Systematic Review and Meta-Analysis

Abstract

Antimicrobial photodynamic therapy (aPDT) is a method that does not seem to promote antimicrobial resistance. Photosensitizers (PS) conjugated with inorganic nanoparticles for the drug-delivery system have the purpose of enhancing the efficacy of aPDT. The present study was to perform a systematic review and meta-analysis of the efficacy of aPDT mediated by PS conjugated with inorganic nanoparticles. The PubMed, Scopus, Web of Science, Science Direct, Cochrane Library, SciELO, and Lilacs databases were searched. OHAT Rob toll was used to assess the risk of bias. A random effect model with an odds ratio (OR) and effect measure was used. Fourteen articles were able to be included in the present review. The most frequent microorganisms evaluated were Staphylococcus aureus and Escherichia coli, and metallic and silica nanoparticles were the most common drug-delivery systems associated with PS. Articles showed biases related to blinding. Significant results were found in aPDT mediated by PS conjugated with inorganic nanoparticles for overall reduction of microorganism cultured in suspension (OR = 0.19 [0.07; 0.67]/p-value = 0.0019), E. coli (OR = 0.08 [0.01; 0.52]/p-value = 0.0081), and for Gram-negative bacteria (OR = 0.12 [0.02; 0.56/p-value = 0.0071). This association approach significantly improved the efficacy in the reduction of microbial cells. However, additional blinding studies evaluating the efficacy of this therapy over microorganisms cultured in biofilm are required.

Keywords: Escherichia coli; Staphylococcus aureus; antimicrobial photodynamic therapy; drug-delivery system; inorganic nanoparticles; meta-analysis; systematic review.

Figure 1

Flowchart based on the PRISMA statement.

Figure 2

Illustration of meta-analysis and quantitative approaches. The experimental group was formed by aPDT mediated by photosensitizers conjugated inorganic nanoparticles and the control group was formed by aPDT only. (A) The results of the meta-analysis are illustrated in a forest plot for the overall viability of microbial cells. (B) Funnel plot analysis shows the absence of publication bias. OR = odds ratio; CI = confidence interval; W: weight [29,30,31,32,34,36,37,38,40,41].

Figure 3

Illustration of meta-analysis and quantitative approaches. The experimental group was formed by aPDT mediated by photosensitizer conjugated inorganic nanoparticles and the control group was formed by aPDT only. (A) The results of the meta-analysis are illustrated in a forest plot for the viability of S. aureus. (B) Trim-and-fill results for the viability of S. aureus show the presence of publication biases. (C). The results of the meta-analysis are illustrated in a forest plot for the viability of E. coli. (D) Trim-and-fill results for the viability of E. coli show the presence of publication and meta-analysis biases. OR = odds ratio; CI = confidence interval; W: weight. TE = estimated mean; seTE = estimated standard deviation [29,30,31,36,38,40,41].

Figure 4

Illustration of meta-analysis and quantitative approaches. The experimental group was formed by aPDT mediated by photosensitizers conjugated inorganic nanoparticles and the control group was formed by aPDT only. (A) The results of meta-analysis illustrated in a forest plot for the viability of microbial cells cultured in suspension and treated with MB-mediated aPDT with or without photosensitizers conjugated with inorganic nanoparticles. (B) Trim-and-fill results for the viability of microbial cells cultured in suspension and treated with MB-mediated aPDT with or without photosensitizers conjugated with inorganic nanoparticles show the presence of publication and meta-analysis biases. (C) The results of meta-analysis illustrated in a forest plot for viability microbial cells cultured in biofilm. (D) Trim-and-fill results for viability microbial cells cultured in biofilm show the absence of publication bias. OR = odds ratio; CI = confidence interval; W: weight. TE = estimated mean; seTE = estimated standard deviation [29,32,33,34,35,36,38,41].

Figure 5

Illustration of meta-analysis and quantitative approaches. The experimental group was formed by aPDT mediated by photosensitizers conjugated inorganic nanoparticles and the control group was formed by aPDT only. (A) The results of the meta-analysis illustrated in a forest plot for the viability of Gram-positive bacteria cultivated in suspension. (B) Trim-and-fill results for the viability of Gram-positive bacteria cultured in suspension show the absence of publication and meta-analysis biases. (C) The results of the meta-analysis illustrated in a forest plot for viability Gram-negative bacteria cultivated in suspension. (D) Trim-and-fill results for Gram-negative bacteria cultivated in suspension presence of publication and meta-analysis biases. OR = odds ratio; CI = confidence interval; W: weight. TE = estimated mean; seTE = estimated standard deviation [29,30,31,33,34,36,38,40,41].