Encapsulation of Photothermal Nanoparticles in Stealth and pH-Responsive Micelles for Eradication of Infectious Biofilms In Vitro and In Vivo.
Ruifang GaoLinzhu SuTianrong YuJian LiuHenny C Van der MeiYijin RenGaojian ChenLinqi ShiBrandon W PetersonHenk J BusscherPublished in: Nanomaterials (Basel, Switzerland) (2021)
Photothermal nanoparticles can be used for non-antibiotic-based eradication of infectious biofilms, but this may cause collateral damage to tissue surrounding an infection site. In order to prevent collateral tissue damage, we encapsulated photothermal polydopamine-nanoparticles (PDA-NPs) in mixed shell polymeric micelles, composed of stealth polyethylene glycol (PEG) and pH-sensitive poly(β-amino ester) (PAE). To achieve encapsulation, PDA-NPs were made hydrophobic by electrostatic binding of indocyanine green (ICG). Coupling of ICG enhanced the photothermal conversion efficacy of PDA-NPs from 33% to 47%. Photothermal conversion was not affected by micellar encapsulation. No cytotoxicity or hemolytic effects of PEG-PAE encapsulated PDA-ICG-NPs were observed. PEG-PAE encapsulated PDA-ICG-NPs showed good penetration and accumulation in a Staphylococcus aureus biofilm. Penetration and accumulation were absent when nanoparticles were encapsulated in PEG-micelles without a pH-responsive moiety. PDA-ICG-NPs encapsulated in PEG-PAE-micelles found their way through the blood circulation to a sub-cutaneous infection site after tail-vein injection in mice, yielding faster eradication of infections upon near-infrared (NIR) irradiation than could be achieved after encapsulation in PEG-micelles. Moreover, staphylococcal counts in surrounding tissue were reduced facilitating faster wound healing. Thus, the combined effect of targeting and localized NIR irradiation prevented collateral tissue damage while eradicating an infectious biofilm.
Keyphrases
- drug delivery
- drug release
- cancer therapy
- fluorescence imaging
- staphylococcus aureus
- photodynamic therapy
- candida albicans
- oxide nanoparticles
- pseudomonas aeruginosa
- oxidative stress
- biofilm formation
- helicobacter pylori infection
- wound healing
- helicobacter pylori
- metabolic syndrome
- insulin resistance
- cystic fibrosis
- ionic liquid
- type diabetes
- radiation induced
- dna binding
- binding protein
- peripheral blood
- ultrasound guided