Ficin–Cyclodextrin-Based Docking Nanoarchitectonics of Self-Propelled Nanomotors for Bacterial Biofilm Eradication

Abstract

Development of bioinspired nanomotors showing effective propulsion and cargo delivery capabilities has attracted much attention in the last few years due to their potential use in biomedical applications. However, implementation of this technology in realistic settings is still a barely explored field. Herein, we report the design and application of a multifunctional gated Janus platinum–mesoporous silica nanomotor constituted of a propelling element (platinum nanodendrites) and a drug-loaded nanocontainer (mesoporous silica nanoparticle) capped with ficin enzyme modified with β-cyclodextrins (β-CD). The engineered nanomotor is designed to effectively disrupt bacterial biofilms via H2O2-induced self-propelled motion, ficin hydrolysis of the extracellular polymeric matrix (EPS) of the biofilm, and controlled pH-triggered cargo (vancomycin) delivery. The effective synergic antimicrobial activity of the nanomotor is demonstrated in the elimination of Staphylococcus aureus biofilms. The nanomotor achieves 82% of EPS biomass disruption and a 96% reduction in cell viability, which contrasts with a remarkably lower reduction in biofilm elimination when the components of the nanomotors are used separately at the same concentrations. Such a large reduction in biofilm biomass in S. aureus has never been achieved previously by any conventional therapy. The strategy proposed suggests that engineered nanomotors have great potential for the elimination of biofilms.

Macrocycle-Based Antibacterial Materials

“…(d) Antibiofilm mechanism of the ficin-modified β-CD-capped Janus Pt-MSN nanomotors. Reproduced with permission from ref .…”

“…Combining peptide-modified macrocycles with self-propelled nanomotors is proposed as a new strategy for improving cargo-targeting delivery capabilities to inhibit bacteria and biofilms . For example, a Janus platinum-mesoporous silica nanoparticle (Pt-MSN) nanomotor was constructed to disrupt and eliminate bacterial biofilms effectively (Figure d) . This can be attributed to the synergistic effects of H 2 O 2 -induced self-propelled motion, ficin hydrolysis of the extracellular polymeric matrix, and pH-triggered antibiotic vancomycin delivery.…”

Antibacterial micro/nanomotors: advancing biofilm research to support medical applications

“…In a study conducted by Ramon et al, a pH-responsive H 2 O 2 -driven MNMs (Janus Pt-MSN) was developed (Fig. 2 A) [ 48 ]. Platinum nanodendrites (PtNDs), the driving element, used the high concentration of H 2 O 2 at the infection site to catalyze the production of O 2 , propelling the MNMs to break through bacterial biofilm (Fig.…”

“…I Biofilm content after treatment with SiO 2 -Au nanomotors under NIR irradiation. A–D Reprinted with permission [ 48 ]. Copyright 2023, American Chemical Society.…”

Strategic Structural Control of Polyserotonin Nanoparticles and Their Application as pH-Responsive Nanomotors

“…Among these, harnessing the pH gradient in the physiological milieu for navigation and motion control of MNMs represents a novel and intelligent approach [ 12 , 13 , 14 , 15 , 16 ]. This mainly involves the modification of pH-responsive media such as polymers or catalytic materials with pH-dependent activities on the MNM surface, and the motion direction and enhancement are predominantly achieved through alterations in the reactions of pH-responsive media and substrate [ 17 , 18 , 19 ]. However, while loading pH-responsive media onto nanomotors enhances their adaptability to varying pH environments, it tends to occupy active sites on the nanomotor surface, potentially impeding the loading of fuel by MNMs.…”