Stimuli-responsive nanocarriers for bacterial biofilm treatment

Abstract

Bacterial biofilm infections have been threatening the human’s life and health globally for a long time because they typically cause chronic and persistent infections. Traditional antibiotic therapies can hardly eradicate biofilms in many cases, as biofilms always form a robust fortress for pathogens inside, inhibiting the penetration of drugs. To address the issues, many novel drug carriers emerged as promising strategies for biofilm treatment. Among them, stimuli-responsive nanocarriers have attracted much attentions for their intriguing physicochemical properties, such as tunable size, shape and surface chemistry, especially smart drug release characteristic. Based on the microenvironmental difference between biofilm infection sites and normal tissue, many stimuli, such as bacterial products accumulating in biofilms (enzymes, glutathione, etc.), lower pH and higher H 2 O 2 levels, have been employed and proved in favor of “on-demand” drug release for biofilm elimination. Additionally, external stimuli including light, heat, microwave and magnetic fields are also able to control the drug releasing behavior artificially. In this review, we summarized recent advances in stimuli-responsive nanocarriers for combating biofilm infections, and mainly, focusing on the different stimuli that trigger the drug release. 摘要 细菌生物膜常造成长期, 顽固的感染, 因此长久以来都严重威胁着全球人类的生命健康。 由于生物膜会为内部病原体建造其保护性屏障, 阻碍药物的渗透, 因此传统的抗生素疗法通常难以根除生物膜。 为了解决这一问题, 研究人员构建了许多新型的药物载体, 以作为颇具前景的生物膜治疗策略。 其中, 刺激响应型纳米载体具有有趣的物理-化学性质, 例如尺寸, 形状和表面化学可调节的性质, 特别是智能药物释放性质, 因此吸引了人们的广泛关注。 根据生物膜感染位置和正常组织之间的微环境差异, 人们利用多种刺激物, 比如生物膜内积累的细菌产物 (酶, 谷胱甘肽等), 低pH和高H 2 O 2 水平, 来设计药物的“按需释放”以清除生物膜。 此外, 包括光, 热, 微波和磁场在内的外源刺激, 也可以用于人工控制药物的释放行为。 本篇综述中, 我们总结了刺激响应型纳米载体在对抗细菌生物膜中的最新进展, 并着重于引发药物释放的多种刺激物。 Graphic abstract

Biological properties of Cu-bearing and Ag-bearing titanium-based alloys and their surface modifications: A review of antibacterial aspect

“…Therefore, some substances can act as triggers for the response of antibacterial materials. As for stimulations, in the study of Ding et al (2021) many products of bacteria such as enzymes, lipases, and some external stimuli such as pH, light, and microwaves have been reported. However, most of the process of experiments based on that were conducted in vitro which does not represent a real infection environment.…”

“…The nano-scale size can be similar to the dimensions of water-filled channels in biofilm structures and possesses good affinity with a negatively charged extracellular matrix. Furthermore, their high surface-to-volume ratio also has excellent advantages (Ding et al, 2021). The metals used for these nanoparticles are almost exclusively heavy metals, such as Ag, Cu, zinc (Zn), and ZnO nanoparticles, with Ag particles being more common (Sanchez-Lopez et al, 2020).…”

Nitric oxide-propelled nanomotors for bacterial biofilm elimination and endotoxin removal to treat infected burn wounds

“…39 In the current study, SNO was used as an NO donor to release NO after breakage of S-N linkages by GSH, which is overexpressed in the biofilm matrix. 45 The loading amount of SNO on IO@PMB-SNO NPs was 6.01 mg mg À1 , and Fig. 1h shows NO release profiles after incubation with 5.0 mM of GSH, which simulated the reductive microenvironment in the biofilms.…”

Biofilms: Formation, Research Models, Potential Targets, and Methods for Prevention and Treatment

“…Additionally, triggering biofilm‐disruptive activity in response to pathogenic micro‐environments (e.g., acidic pH, hypoxia, temperature, and pathogen‐derived metabolites) and targeting bacteria specifically (e.g., bacterial exotoxins, outer membrane proteins, d‐amino acids of cell membrane, and competitive displacement) could be other interesting directions. [ 367 , 368 , 369 ] The ultimate goal may concentrate on the development of doable and affordable dosage forms and collaborations with industrial partners to achieve the highest potency and safety with long‐lasting therapeutic effects and minimal cytotoxicity for use in clinics.…”