Multi‐Mode Antibacterial Strategies Enabled by Gene‐Transfection and Immunomodulatory Nanoparticles in 3D‐Printed Scaffolds for Synergistic Exogenous and Endogenous Treatment of Infections

Qu, Xinhua; Wang, Minqi; Wang, Miaochen; Tang, Haozheng; Zhang, Shutao; Yang, Hongtao; Yuan, Weien; Wang, You; Yang, Jianping; Yue, Bing

doi:10.1002/adma.202200096

Cited by 38 publications

(29 citation statements)

References 70 publications

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“…Finally, the cost of synthesis and production of recombinant LL37 is high . Therefore, researchers have developed nanodelivery systems such as mesoporous silica, , metal nanoparticles , and polymer particles to overcome the above limitations of LL37. However, owing to the abiotic nature of these agents and the inability of these chemical synthetic carriers to target the bacteria, they suffer from rapid phagocytosis by the phagocytic system and low efficiency in systematic delivery of LL37.…”

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confidence: 99%

Macrophage-Membrane-Camouflaged Nonviral Gene Vectors for the Treatment of Multidrug-Resistant Bacterial Sepsis

et al. 2022

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Sepsis is a life-threatening disease caused by systemic bacterial infections, with high morbidity and mortality worldwide. As the standard treatment for sepsis, antibiotic therapy faces the challenge of impaired macrophages and drug-resistant bacteria. In this study, we developed a membrane-camouflaged metal−organic framework (MOF) system for plasmid DNA (pDNA) delivery to combat sepsis. The antimicrobial gene LL37 was efficiently encapsulated in the pH-sensitive MOF, and the nanoparticles were decorated with macrophage membranes in a compatible manner. Macrophage membrane coating allows targeted delivery of LL37 to macrophages and creates macrophage factories for the continuous generation of antimicrobial peptides. Compared to naked nanoparticles, primary bone marrow mesenchymal macrophage membrane-modified nanoparticles greatly improved the survival rate of immunodeficient septic mice through the synergistic effect of efficient gene therapy and inflammatory cytokine sequestration. This study demonstrates an effective membrane biomimetic strategy for efficiently delivering pDNA, offering an excellent option for overcoming sepsis.

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confidence: 99%

Macrophage-Membrane-Camouflaged Nonviral Gene Vectors for the Treatment of Multidrug-Resistant Bacterial Sepsis

et al. 2022

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“…Unfortunately, many previous reports were at the stage of “ proof of concept ”; they did not conform strictly to a specific application. According to the papers we have screened, major flaws in our current reporting on developing antibacterial surfaces for implantable medical devices are ( Table 7 includes some typical examples [ 18 , 272 , 273 , 274 , 275 , 276 , 277 , 278 ]) (1) many reports are lack of comprehensive understanding of the requirements of a specific application or even have no clear indication of use (Cases 2, 3, 7, and 8 in Table 7 ); as a result, it is hard to ensure the effectiveness and safety of such designs because the incidence and pathogens of DAIs are site-specific [ 66 ] and the biocompatibility of biomaterials is referred to specific applications [ 279 ]. (2) Some reports choose testing assays that do not closely relate to the intended use.…”

Section: Directions To Improve the Quality Of Antibacterial Reportsmentioning

confidence: 99%

Antibacterial Designs for Implantable Medical Devices: Evolutions and Challenges

Cao

Qiao

Qin

2022

JFB

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The uses of implantable medical devices are safer and more common since sterilization methods and techniques were established a century ago; however, device-associated infections (DAIs) are still frequent and becoming a leading complication as the number of medical device implantations keeps increasing. This urges the world to develop instructive prevention and treatment strategies for DAIs, boosting the studies on the design of antibacterial surfaces. Every year, studies associated with DAIs yield thousands of publications, which here are categorized into four groups, i.e., antibacterial surfaces with long-term efficacy, cell-selective capability, tailored responsiveness, and immune-instructive actions. These innovations are promising in advancing the solution to DAIs; whereas most of these are normally quite preliminary “proof of concept” studies lacking exact clinical scopes. To help identify the flaws of our current antibacterial designs, clinical features of DAIs are highlighted. These include unpredictable onset, site-specific incidence, and possibly involving multiple and resistant pathogenic strains. The key point we delivered is antibacterial designs should meet the specific requirements of the primary functions defined by the “intended use” of an implantable medical device. This review intends to help comprehend the complex relationship between the device, pathogens, and the host, and figure out future directions for improving the quality of antibacterial designs and promoting clinical translations.

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“…Besides the M2 polarization of macrophages, the abnormal increase in the proportion of myeloid-derived suppressor cells (MDSCs) also contributed to the immunosuppressive environment at the infectious site. Qu and co-workers designed the LL37@ZIF8-LL37 nanosystem, which was laden with an antibacterial peptide plasmid (LL37 plasmid) and modified with the antibacterial LL37 peptide on the surface . The nanosystem could kill Staphylococcus aureus ( S. aureus ) and sustain the intracellular production of LL37 peptide after translation of the LL37 plasmid to prolong the antimicrobial effect.…”

Section: Nanosystems For Activating Immune Responses To Treat Bacteri...mentioning

confidence: 99%

“…Qu and co-workers designed the LL37@ZIF8-LL37 nanosystem, which was laden with an antibacterial peptide plasmid (LL37 plasmid) and modified with the antibacterial LL37 peptide on the surface. 59 The nanosystem could kill Staphylococcus aureus (S. aureus) and sustain the intracellular production of LL37 peptide after translation of the LL37 plasmid to prolong the antimicrobial effect. In addition to increasing the level of M1-like cells, LL37@ZIF8-LL37 treatment could decrease the proportion of MDSCs to activate T-cell-related cellular immune responses.…”

Section: Nanosystems For Activating Adaptive Immunitymentioning

confidence: 99%

Nanosystems for Immune Regulation against Bacterial Infections: A Review

Zhang

Chen

Zhao

2022

ACS Appl. Nano Mater.

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The immune system constitutes the fortifications that safeguard the body against bacterial infections. Artificial nanosystems possess many attractive properties including the ability to modulate the immune responses against bacterial infections. On the one hand, antigen-loaded nanosystems have emerged as a promising alternative to convensional vaccines, protecting the host from infection. On the other hand, immunity can be regulated by nanosystems to treat infections caused by bacteria and related diseases. Herein, we initially introduce the recent advances of artificial nanosystems in the development of different vaccines including subunit and toxoid vaccines. Then, we focus on discussing the employment of nanosystems for the activation of immunity, including innate and adaptive immunity, to treat bacteria-induced infectious diseases. In addition, nanosystems with immunosuppressive capabilities are also highlighted, which can restrain the overactivation of immune responses, thereby relieving inflammation in the face of infections. Finally, we discuss current challenges and provide perspectives for future development in this rapidly growing field. Thus, this review is expected to inspire more advanced research of using nanosystems to achieve immune regulation toward practical applications.

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Multi‐Mode Antibacterial Strategies Enabled by Gene‐Transfection and Immunomodulatory Nanoparticles in 3D‐Printed Scaffolds for Synergistic Exogenous and Endogenous Treatment of Infections

Abstract: Figure 9. Schematic illustrating the multi-faceted antimicrobial and immunomodulatory mechanism employed by the 3D-printed implant.

Cited by 38 publications

References 70 publications

Macrophage-Membrane-Camouflaged Nonviral Gene Vectors for the Treatment of Multidrug-Resistant Bacterial Sepsis

Macrophage-Membrane-Camouflaged Nonviral Gene Vectors for the Treatment of Multidrug-Resistant Bacterial Sepsis

Antibacterial Designs for Implantable Medical Devices: Evolutions and Challenges

Nanosystems for Immune Regulation against Bacterial Infections: A Review

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