An efficient antimicrobial depot for infectious site-targeted chemo-photothermal therapy

Abstract

BackgroundSilver and photothermal therapy (PTT) have been widely used for eradicating the drug-resistant bacteria. However, the risks of excess of silver for humans and the low efficiency of PTT still limit their in vivo therapeutic application. Integration of two distinctive bactericides into one entity is a promising platform to improve the efficiency of antimicrobial agents.ResultsIn this study, a chemo-photothermal therapeutic platform based on polydopamine (PDA)-coated gold nanorods (GNRs) was developed. The PDA coating acquired high Ag+ ions loading efficiency and Cy5-SE fluorescent agent labeled glycol chitosan (GCS) conjugation (Ag+-GCS-PDA@GNRs). This platform became positively charged in the low pH environment of the abscess, allowing their accumulation in local infection site as revealed by thermal/florescence imaging. The loaded Ag+ ions was released in a pH-sensitive manner, resulting in selective Ag+ ions delivery to the abscess environment (pH ~ 6.3). More importantly, the ultralow dose of Ag+ ions could effectively damage the bacterial membrane, causing the permeability increase and the heat resistance reduction of the cell membrane, leading to the large improvement on bactericidal efficiency of PTT. On the other hand, the hyperthermia could trigger more Ag+ ions release, resulting in further improvement on bactericidal efficiency of chemotherapy. Combinational chemo-hyperthermia therapy of Ag+-GCS-PDA@GNRs could thoroughly ablate abscess and accelerate wound healing via a synergistic antibacterial effect.ConclusionsOur studies demonstrate that Ag+-GCS-PDA@GNRs is a robust and practical platform for use in chemo-thermal focal infection therapy with outstanding synergistic bacteria ablating.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0348-z) contains supplementary material, which is available to authorized users.

A multifunctional platform with single-NIR-laser-triggered photothermal and NO release for synergistic therapy against multidrug-resistant Gram-negative bacteria and their biofilms

“…S3, TG-NO-B exhibited a high η value of 37.6%, making it very excellent as a promising PTT agent. Furthermore, irreversible thermal ablation of bacteria always occurs at the temperature over 55 °C, but the damage of bacterial cell membranes may enhance permeability and sensitivity to heat, consequently making bacteria more vulnerable and requiring lower photothermal temperatures [20,43]. 100 μg/mL TG-NO-B under the laser irradiation at 0.75 W/cm 2 for 10 min possessed an equilibrium temperature of 49.8 °C, and was selected to explore the following chemo-photothermal synergistic effect against bacteria, considering the destructive effect of NO on bacterial membranes.…”

“…Together, the probable antibacterial mechanism of TG-NO-B is that TG-NO-B specially adsorb onto the bacterial cell membrane, then disrupt the integrity of the membrane via the local hyperthermia and the released NO under NIR laser irradiation, finally lead to leakage of intracellular components like DNAs/ RNAs and induce bacteria death [13,22]. Furthermore, the bacterial cell damage can increase the permeability and sensitivity of bacterial cells to heat and decrease the hyperthermia temperature [20,43]. On the other hand, the hyperthermia caused by PTT can promote NO release (Fig.…”

“…For example, photothermal nanoagents themselves cannot selectively bind to pathogenic bacteria or biofilms, which may inevitably cause undesirable damage the ambient healthy tissues [9,19]. Besides, current working temperatures of PTT are too high (55-60 °C), which can potentially burn the normal skin and other tissues [20]. Moreover, monotherapy is not as effective as expected in treating bacterial infections [21].…”

“…Upon NIR laser irradiation, the NIR-triggered hyperthermia and NO releasing can disrupt the bacterial cell membrane, further cause leakage of intracellular components, and finally induce bacteria death. At the same time, the bacterial cell membrane damage can enhance the permeability and sensitivity to heat and lower the hyperthermia temperature [20]. Furthermore, the hyperthermia can also promote NO release, which may further damage the bacterial cells.…”

Nano-Based Drug Delivery or Targeting to Eradicate Bacteria for Infection Mitigation: A Review of Recent Advances

“…The MRSA-infected wound in rabbit back was topically administered by the nanoparticles. The regenerated skin after treatment of nanocomposite showed an appearance like normal skin, with 92% wound closure, whereas the wound treated by gauze only revealed 67% closure after 16 d. Liu et al (2018) developed chemo-photothermal therapy against subcutaneous infection based on polydopamine-coated Au nanorods. Polydopamine coating achieved efficient antibacterial Ag loading in the nanorods.…”