Synergistic antimicrobial photodynamic therapy using gated mesoporous silica nanoparticles containing curcumin and polymyxin B.

Photodynamic Therapy is a therapy based on combining a non-toxic compound, known as photosensitizer (PS), and irradiation with light of the appropriate wavelength to excite the PS molecule. The photon absorption by the PS leads to reactive oxygen species generation and a subsequent oxidative burst that causes cell damage and death. In this work, we report an antimicrobial nanodevice that uses the activity of curcumin (Cur) as a PS for antimicrobial Photodynamic Therapy (aPDT), based on mesoporous silica nanoparticles in which the action of the classical antibiotic PMB is synergistically combined with the aPDT properties of curcumin to combat bacteria. The synergistic effect of the designed gated device in combination with irradiation with blue LED light (470 nm) is evaluated against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus epidermidis. The results show that the nanodevice exhibits a noteworthy antibacterial activity against these microorganisms, a much more significant effect than free Cur and PMB at equivalent concentrations. Thus, 0.1 µg/mL of MSNs-Cur-PMB eliminates a bacterial concentration of about 105 CFU/mL of E. coli, while 1 µg/mL of MSNs-Cur-PMB is required for P. aeruginosa and S. epidermidis. In addition, antibiofilm activity against the selected bacteria was also tested. We found that 0.1 mg/mL of MSNs-Cur-PMB inhibited 99 % biofilm formation for E. coli, and 1 mg/mL of MSNs-Cur-PMB achieved 90 % and 100 % inhibition of biofilm formation for S. epidermidis and P. aeruginosa, respectively.

Exploring the Synergy between Nano-Formulated Linezolid and Polymyxin B as a Gram-Negative Effective Antibiotic Delivery System Based on Mesoporous Silica Nanoparticles.

Antimicrobial resistance is a current silent pandemic that needs new types of antimicrobial agents different from the classic antibiotics that are known to lose efficiency over time. Encapsulation of antibiotics inside nano-delivery systems could be a promising, effective strategy that is able to delay the capability of pathogens to develop resistance mechanisms against antimicrobials. These systems can be adapted to deliver already discovered antibiotics to specific infection sites in a more successful way. Herein, mesoporous silica nanomaterials are used for an efficient delivery of a linezolid gram-positive antibiotic that acts synergistically with gram-negative antimicrobial polymyxin B. For this purpose, linezolid is encapsulated in the pores of the mesoporous silica, whose outer surface is coated with a polymyxin B membrane disruptor. The nanomaterial showed a good controlled-release performance in the presence of lipopolysaccharide, found in bacteria cell membranes, and the complete bacteria E. coli DH5α. The performed studies demonstrate that when the novel formulation is near bacteria, polymyxin B interacts with the cell membrane, thereby promoting its permeation. After this step, linezolid can easily penetrate the bacteria and act with efficacy to kill the microorganism. The nano-delivery system presents a highly increased antimicrobial efficacy against gram-negative bacteria, where the use of free linezolid is not effective, with a fractional inhibitory concentration index of 0.0063 for E. coli. Moreover, enhanced toxicity against gram-positive bacteria was confirmed thanks to the combination of both antibiotics in the same nanoparticles. Although this new nanomaterial should be further studied to reach clinical practice, the obtained results pave the way to the development of new nanoformulations which could help in the fight against bacterial infections.

Fluorogenic Detection of Human Serum Albumin Using Curcumin-Capped Mesoporous Silica Nanoparticles.

Mesoporous silica nanoparticles loaded with rhodamine B and capped with curcumin are used for the selective and sensitive fluorogenic detection of human serum albumin (HSA). The sensing mesoporous silica nanoparticles are loaded with rhodamine B, decorated with aminopropyl moieties and capped with curcumin. The nanoparticles selectively release the rhodamine B cargo in the presence of HSA. A limit of detection for HSA of 0.1 mg/mL in PBS (pH 7.4)-acetonitrile 95:5 v/v was found, and the sensing nanoparticles were used to detect HSA in spiked synthetic urine samples.

Simple Endotoxin Detection Using Polymyxin-B-Gated Nanoparticles.

A nanodevice based on mesoporous silica nanoparticles with rhodamine B in the pore framework, functionalized with carboxylates on the outer surface and capped with the cationic polymyxin B peptide, was used to selectively detect endotoxin in aqueous solutions with a limit of detection in the picomolar range.