Encapsulation of Photothermal Nanoparticles in Stealth and pH-Responsive Micelles for Eradication of Infectious Biofilms In Vitro and In Vivo.

Ruifang Gao,Ruifang Gao,Ruifang Gao,Jian Liu,Linzhu Su,Tianrong Yu,Brandon W Peterson,Linzhu Su,Yijin Ren,Yijin Ren,Gaojian Chen,Henny C Van Der Mei,Henny C Van Der Mei,Henk J Busscher,Henk J Busscher,Brandon W Peterson,Linqi Shi,Tianrong Yu,Linzhu Su

doi:10.3390/nano11123180

Abstract

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.

Highlights

Photothermal nanoparticles convert light to heat [1,2] and are considered for the control of tumors and infectious biofilms, which are becoming more and more difficult through the increasing occurrence of antibiotic-resistant bacterial strains [3]
This paper describes the coating of PDA-NPs with indocyanine green (ICG) to make hydrophobic PDA-ICG-NPs that can be encapsulated in stealth, pH-responsive polyethylene glycol (PEG)-poly(β-amino ester) (PAE)
Coating with ICG could be inferred from the development of a broad UV-vis absorption band due to ICG in the spectrum of PDA-ICG-NPs that persisted upon micellar encapsulation (Figure 1b)

Summary

Introduction

Photothermal nanoparticles convert light to heat [1,2] and are considered for the control of tumors and infectious biofilms, which are becoming more and more difficult through the increasing occurrence of antibiotic-resistant bacterial strains [3]. Nanomaterials 2021, 11, 3180 centimeter-sized tumors, irradiation of a micrometer-sized infection site will usually cause collateral tissue damage due to the heat generated by photothermal nanoparticles. Near-infrared (NIR) irradiation is preferred for photothermal treatment due to its “deep” penetration in tissue that is clinically still confined to around 5 to 10 mm maximally [4]. Different materials such as carbon quantum dots [5], graphene [6], noble metals [7], copper chalcogenide nanomaterials [8], polyaniline [9] and polydopamine [10]

Results

Discussion

Conclusion