Nanotoxoid vaccination protects against opportunistic bacterial infections arising from immunodeficiency.

The rise in nosocomial infections caused by multidrug-resistant pathogens is a major public health concern. Patients taking immunosuppressants or chemotherapeutics are naturally more susceptible to infections. Thus, strategies for protecting immunodeficient individuals from infections are of great importance. Here, we investigate the effectiveness of a biomimetic nanotoxoid vaccine in defending animals with immunodeficiency against Pseudomonas aeruginosa. The nanotoxoids use a macrophage membrane coating to sequester and safely present bacterial virulence factors that would otherwise be too toxic to administer. Vaccination with the nanoformulation results in rapid and long-lasting immunity, protecting against lethal infections despite severe immunodeficiency. The nanovaccine can be administered through multiple routes and is effective in both pneumonia and septicemia models of infection. Mechanistically, protection is mediated by neutrophils and pathogen-specific antibodies. Overall, nanotoxoid vaccination is an attractive strategy to protect vulnerable patients and could help to mitigate the threat posed by antibiotic-resistant superbugs.

Biomimetic Neutrophil Nanotoxoids Elicit Potent Immunity against Acinetobacter baumannii in Multiple Models of Infection.

Acinetobacter baumannii is a leading cause of antibiotic-resistant nosocomial infections with high mortality rates, yet there is currently no clinically approved vaccine formulation. During the onset of A. baumannii infection, neutrophils are the primary responders and play a major role in resisting the pathogen. Here, we design a biomimetic nanotoxoid for antivirulence vaccination by using neutrophil membrane-coated nanoparticles to safely capture secreted A. baumannii factors. Vaccination with the nanotoxoid formulation rapidly mobilizes innate immune cells and promotes pathogen-specific adaptive immunity. In murine models of pneumonia, septicemia, and superficial wound infection, immunization with the nanovaccine offers significant protection, improving survival and reducing signs of acute inflammation. Lower bacterial burdens are observed in vaccinated animals regardless of the infection route. Altogether, neutrophil nanotoxoids represent an effective platform for eliciting multivalent immunity to protect against multidrug-resistant A. baumannii in a wide range of disease conditions.

Organotropic Targeting of Biomimetic Nanoparticles to Treat Lung Disease.

Active targeting strategies aimed at improving drug homing while reducing systemic toxicity are widely being pursued in the growing field of nanomedicine. While they can be effective, these approaches often require the identification of cell-specific targets and in-depth knowledge of receptor binding interactions. More recently, there has been significant interest in biomimetic nanoformulations capable of replicating the properties of naturally occurring systems. In particular, the advent of cell membrane coating nanotechnology has enabled researchers to leverage the inherent tropisms displayed by living cells, bypassing many of the challenges associated with traditional bottom-up nanoengineering. In this work, we report on a biomimetic organotropic nanodelivery system for localizing therapeutic payloads to the lungs. Metastatic breast cancer exosomes, which are lung tropic due to their unique surface marker expression profile, are used to coat nanoparticle cores loaded with the anti-inflammatory drug dexamethasone. In vivo, these nanoparticles demonstrate enhanced accumulation in lung tissue and significantly reduce proinflammatory cytokine burden in a lung inflammation model. Overall, this work highlights the potential of using biomimetic organ-level delivery strategies for the management of certain disease conditions.

Nanodelivery of STING agonists against cancer and infectious diseases.

Vaccination is a modality that has been widely explored for the treatment of various diseases. To increase the potency of vaccine formulations, immunostimulatory adjuvants have been regularly exploited, and the stimulator of interferon genes (STING) signaling pathway has recently emerged as a remarkable therapeutic target. STING is an endogenous protein on the endoplasmic reticulum that is a downstream sensor to cytosolic DNA. Upon activation, STING initiates a series of intracellular signaling cascades that ultimately generate potent type I interferon-mediated immune responses. Both natural and synthetic agonists have been used to stimulate the STING pathway, but they are usually administered locally due to low bioavailability, instability, and difficulty in bypassing the plasma membrane. With excellent pharmacokinetic profiles and versatility, nanocarriers can address many of these challenges and broaden the application of STING vaccines. Along these lines, STING-inducing nanovaccines are being developed to address a wide range of diseases. In this review, we discuss the recent advances in STING nanovaccines for anticancer, antiviral, and antibacterial applications.

Physical Disruption of Solid Tumors by Immunostimulatory Microrobots Enhances Antitumor Immunity.

The combination of immunotherapy with other forms of treatment is an emerging strategy for boosting antitumor responses. By combining multiple modes of action, these combinatorial therapies can improve clinical outcomes through unique synergisms. Here, a microrobot-based strategy that integrates tumor tissue disruption with biological stimulation is shown for cancer immunotherapy. The microrobot is fabricated by loading bacterial outer membrane vesicles onto a self-propelling micromotor, which can react with water to generate a propulsion force. When administered intratumorally to a solid tumor, the disruption of the local tumor tissue coupled with the delivery of an immunostimulatory payload leads to complete tumor regression. Additionally, treatment of the primary tumor results in the simultaneous education of the host immune system, enabling it to control the growth of distant tumors. Overall, this work introduces a distinct application of microrobots in cancer immunotherapy and offers an attractive strategy for amplifying cancer treatment efficacy when combined with conventional therapies.