Seeking Cells, Targeting Bacteria: A Cascade-Targeting Bacteria-Responsive Nanosystem for Combating Intracellular Bacterial Infections.

Intracellular bacteria pose a great challenge to antimicrobial therapy due to various physiological barriers at both cellular and bacterial levels, which impede drug penetration and intracellular targeting, thereby fostering antibiotic resistance and yielding suboptimal treatment outcomes. Herein, a cascade-target bacterial-responsive drug delivery nanosystem, MM@SPE NPs, comprising a macrophage membrane (MM) shell and a core of SPE NPs. SPE NPs consist of phenylboronic acid-grafted dendritic mesoporous silica nanoparticles (SP NPs) encapsulated with epigallocatechin-3-gallate (EGCG), a non-antibiotic antibacterial component, via pH-sensitive boronic ester bonds are introduced. Upon administration, MM@SPE NPs actively home in on infected macrophages due to the homologous targeting properties of the MM shell, which is subsequently disrupted during cellular endocytosis. Within the cellular environment, SPE NPs expose and spontaneously accumulate around intracellular bacteria through their bacteria-targeting phenylboronic acid groups. The acidic bacterial microenvironment further triggers the breakage of boronic ester bonds between SP NPs and EGCG, allowing the bacterial-responsive release of EGCG for localized intracellular antibacterial effects. The efficacy of MM@SPE NPs in precisely eliminating intracellular bacteria is validated in two rat models of intracellular bacterial infections. This cascade-targeting responsive system offers new solutions for treating intracellular bacterial infections while minimizing the risk of drug resistance.

Advances in reparative materials for infectious bone defects and their applications in maxillofacial regions.

Infectious bone defects are characterized by the partial loss or destruction of bone tissue resulting from bacterial contaminations subsequent to diseases or external injuries. Traditional bone transplantation and clinical methods are insufficient in meeting the treatment demands for such diseases. As a result, researchers have increasingly focused on the development of more sophisticated biomaterials for improved therapeutic outcomes in recent years. This review endeavors to investigate specific reparative materials utilized for the treatment of infectious bone defects, particularly those present in the maxillofacial region, with a focus on biomaterials capable of releasing therapeutic substances, functional contact biomaterials, and novel physical therapy materials. These biomaterials operate via heightened antibacterial or osteogenic properties in order to eliminate bacteria and/or stimulate bone cells regeneration in the defect, ultimately fostering the reconstitution of maxillofacial bone tissue. Based upon some successful applications of new concept materials in bone repair of other parts, we also explore their future prospects and potential uses in maxillofacial bone repair later in this review. We highlight that the exploration of advanced biomaterials holds promise in establishing a solid foundation for the development of more biocompatible, effective, and personalized treatments for reconstructing infectious maxillofacial defects.

A macrophage cell membrane-coated cascade-targeting photothermal nanosystem for combating intracellular bacterial infections.

Current antibacterial interventions encounter formidable challenges when confronting intracellular bacteria, attributable to their clustering within phagocytes, particularly macrophages, evading host immunity and resisting antibiotics. Herein, we have developed an intelligent cell membrane-based nanosystem, denoted as MM@DAu NPs, which seamlessly integrates cascade-targeting capabilities with controllable antibacterial functions for the precise elimination of intracellular bacteria. MM@DAu NPs feature a core comprising D-alanine-functionalized gold nanoparticles (DAu NPs) enveloped by a macrophage cell membrane (MM) coating. Upon administration, MM@DAu NPs harness the intrinsic homologous targeting ability of their macrophage membrane to infiltrate bacteria-infected macrophages. Upon internalization within these host cells, exposed DAu NPs from MM@DAu NPs selectively bind to intracellular bacteria through the bacteria-targeting agent, D-alanine present on DAu NPs. This intricate process establishes a cascade mechanism that efficiently targets intracellular bacteria. Upon exposure to near-infrared irradiation, the accumulated DAu NPs surrounding intracellular bacteria induce local hyperthermia, enabling precise clearance of intracellular bacteria. Further validation in animal models infected with the typical intracellular bacteria, Staphylococcus aureus, substantiates the exceptional cascade-targeting efficacy and photothermal antibacterial potential of MM@DAu NPs in vivo. Therefore, this integrated cell membrane-based cascade-targeting photothermal nanosystem offers a promising approach for conquering persistent intracellular infections without drug resistance risks. STATEMENT OF SIGNIFICANCE: Intracellular bacterial infections lead to treatment failures and relapses because intracellular bacteria could cluster within phagocytes, especially macrophages, evading the host immune system and resisting antibiotics. Herein, we have developed an intelligent cell membrane-based nanosystem MM@DAu NPs, which is designed to precisely eliminate intracellular bacteria through a controllable cascade-targeting photothermal antibacterial approach. MM@DAu NPs combine D-alanine-functionalized gold nanoparticles with a macrophage cell membrane coating. Upon administration, MM@DAu NPs harness the homologous targeting ability of macrophage membrane to infiltrate bacteria-infected macrophages. Upon internalization, exposed DAu NPs from MM@DAu NPs selectively bind to intracellular bacteria through the bacteria-targeting agent, enabling precise clearance of intracellular bacteria through local hyperthermia. This integrated cell membrane-based cascade-targeting photothermal nanosystem offers a promising avenue for conquering persistent intracellular infections without drug resistance risks.