Combatting Infections with Nanomedicine
Authors: Ronnie H. Fang, Liangfang Zhang
Journal: Advanced Healthcare Materials (2018)

The incidence of antibiotic resistance has been growing at an alarming rate, making bacterial infections an increasingly important problem within the context of global health. Multiresistant bacterial strains are now commonplace, and first-line antibiotics often fail in the clinic. As a result, there is now an acute public awareness regarding the emergence of highly resistant "superbug" pathogens that cannot be treated with most known antibiotics. The driving force behind this epidemic has been the systematic overuse and overprescription of antibiotics, which provide the selective pressure on bacteria that promotes their resistance. Unfortunately, the development of new drug candidates is currently at a standstill. Without effective treatments, significantly worsened clinical outcomes can be expected for patients contracting bacterial infections, where those that were once easily treatable may now quickly become fatal. Ultimately, an increased rate of serious illness caused by bacteria will present a major burden on healthcare systems, as well as on the global economy. The seriousness of this issue has driven researchers to work on developing new ways of treating and diagnosing infections that will help clinicians to navigate a "postantibiotic" world. One research direction that has been actively pursued in recent years is the application of nanotechnology toward addressing the problem of antibiotic resistance. Over the past several decades, the field of nanomedicine has grown significantly from its cancer drug delivery roots and now encompasses a wide range of applications, including the management of infectious diseases. At their small size scale, nanomaterials exhibit unique properties that can be leveraged to improve upon the sensitivity, specificity, throughput, and potency of current modalities. This special issue of Advanced Healthcare Materials focuses specifically on nanoscale solutions for addressing infections. With innovative engineering and an increased understanding of how nanomaterials and pathogens interact with each other, more effective, preventative, therapeutic, and diagnostic measures can be developed and successfully translated to the clinic. Knowledge regarding the material properties of nanostructures is important for understanding how they can be used against pathogens. For example, Zheng et al. describe how silver nanoparticles have been taken advantage of for their inherent antibacterial properties, with specific discussion on their mechanism of action and how chemistry, size, and shape, affect their activity (see article number 1701503). Xu et al. cover the design and application of metal and metal oxide nanoparticles, which have unique optical, magnetic, and electrical attributes enabling their use for both the diagnosis and treatment of infections (see article number 1701392). Various nanomaterials can help to reduce the formation of biofilms, and nanopatterned surfaces designed to be nonfouling have been used to address implant-associated bacterial growth, as described by Webster et al. (see article number 1800103). Chen et al. cover the emerging use of graphene-based materials toward antimicrobial nanomedicine; the use of these materials as colloids, coatings, and phototherapy agents is discussed (see article number 1701406). In contrast to traditional bactericidal modalities, antivirulence therapy has become an appealing method for treating bacteria in a way that may help to stem the development of resistance. Along these lines, Zhang et al. report on the application of biomimetic cell membrane-coated nanoparticles for the broad-spectrum neutralization of a wide range of pore-forming toxins (see article number 1701366). While significant attention has been placed on bacterial infection, there are also opportunities for applying nanomedicine to other types of pathogens, including for parasitic worms, as covered by Wang et al. (see article number 1701494). Besides taking advantage of their inherent antibacterial properties, nanomaterials can also be used as a means of improving the potency of known therapeutic compounds. By engineering nanoformulations to help improve the delivery or sustain the release of antimicrobial agents, treatment platforms with better biological activity can be developed. Loh et al. describe recent advances in nanoparticle-based formulations, including those based on metals, polymers, and lipids, for treating resistant bacteria, and various design aspects are considered (see article number 1701400). In the work by Yang et al., different anionic hydrogel systems are screened to identify a formulation that allows for the safe and controlled delivery of the antibiotic polymyxin B for treating wounds infected with Pseudomonas aeruginosa (see article number 1701388). Schoenfisch et al. review various macromolecular scaffolds that have been reported for the release of nitric oxide, which can be used for the treatment of bacterial biofilms in a manner that does not generate resistance (see article number 1800155). The interplay between pathogens and the immune system is an important part of how infections progress in a host. It is no accident that those who are the most susceptible to infection generally have compromised immune systems, which is the case for many patients in hospital environments. It is often highly desirable to augment and manipulate the immune system in order to better promote antibacterial immunity. Hu et al. discuss how nanoparticles and nanomaterials have been used to engineer potent vaccines, which represent a viable strategy for prophylactically managing bacterial infections, even in a postantibiotic era (see article number 1701395). However, there are also instances in which an overactive immune response can be highly damaging, as is the case with bacteria-mediated sepsis. Gho et al. report on the screening and repurposing of commercially available drugs for the specific purpose of mitigating inflammatory responses induced by the outer membrane vesicles secreted from gram-negative bacteria (see article number 1701476). Furthermore, even in the absence of pathogenesis, nanomaterial exposure can have a profound impact on the host immune system, and Feng et al. find that the oral administration of carbon nanotubes can increase intestinal permeability, leading to inflammatory responses that can alter the gut microbiota composition (see article number 1701313). Besides prevention and treatment, detection is another important aspect in the clinical management of infections that can benefit from the use of nanotechnology. With the overprescription of antibiotics being a major cause of resistance, it is now more important than ever to correctly identify the offending pathogen so that an appropriate treatment plan can be provided. Yu et al. review the use of surface-enhanced Raman scattering for bacteria-related applications, including as a means of diagnosis and for fundamental studies; various commonly used nanomaterials and surface modifications are discussed (see article number 1701335). Abbas et al. report on the use of gold nanoplate-enhanced chemiluminescence, in combination with macromolecular shielding using polymers conjugated with antibodies, for the rapid diagnosis of bacteria (see article number 1701506). The development of techniques that can be performed on-site is of high importance, especially for developing countries where sophisticated equipment may not be available. Along these lines, Qu et al. develop a gold nanocluster-based point-of-care sensor array capable of discriminating multiple kinds of bacteria with high accuracy (see article number 1701370). Overall, the publications presented in this special issue represent a diverse intersection of many different disciplines, all working together to help advance nanomedicine with regards to the management of infectious diseases. With the continued efforts of researchers working in this field, a significant and lasting impact can be made on the clinical landscape. Ronnie H. Fang is an Assistant Project Scientist in the Department of NanoEngineering at the University of California San Diego. He received his Ph.D. in nanoengineering at the University of California San Diego. His research is focused on leveraging biomimetic nanoparticles for drug delivery and immunoengineering applications. Liangfang Zhang is a Professor in the Department of NanoEngineering and Moores Cancer Center at the University of California San Diego. He received his Ph.D. in Chemical and Biomolecular Engineering at the University of Illinois at Urbana-Champaign. His research aims to create cutting-edge biomimetic nanotechnologies and exploit them for various biomedical applications with a particular focus on drug delivery, biodetoxification and vaccination.