Intratumoral immunotherapy using platelet-cloaked nanoparticles enhances antitumor immunity in solid tumors.

Intratumoral immunotherapy is an emerging modality for the treatment of solid tumors. Toll-like receptor (TLR) agonists have shown promise for eliciting immune responses, but systemic administration often results in the development of adverse side effects. Herein, we investigate whether localized delivery of the TLR agonist, resiquimod (R848), via platelet membrane-coated nanoparticles (PNP-R848) elicits antitumor responses.

Selective cell death of latently HIV-infected CD4 T cells mediated by autosis inducing nanopeptides.

Despite significant advances in the treatment of human immunodeficiency virus type-1 (HIV) infection, antiretroviral therapy only suppresses viral replication but is unable to eliminate infection. Thus, discontinuation of antiretrovirals results in viral reactivation and disease progression. A major reservoir of HIV latent infection resides in resting central memory CD4 T cells (T) that escape clearance by current therapeutic regimens and will require novel strategies for elimination.

Induction of a Na/K-ATPase-dependent form of autophagy triggers preferential cell death of human immunodeficiency virus type-1-infected macrophages.

Although antiretroviral therapy is highly effective in suppressing human immunodeficiency virus type-1 (HIV) replication, treatment has failed to eliminate viral reservoirs and discontinuation of treatment results in viral reactivation. Here, we demonstrate that peptides Tat-vFLIP-α2 and Tat-Beclin 1/BECN1 which have been shown to induce a Na/K-ATPase- and a macroautophagy/autophagy-dependent form of cell death, autosis, can preferentially kill HIV-infected macrophages while preventing virological rebound. To improve bioavailability and drug delivery, Tat-vFLIP-α2 was encapsulated into biodegradable PLGA (poly lactic-co-glycolic acid)-lipid-PEG (polyethylene glycol) nanoparticles for long-lasting intracellular delivery.

Biomimetic Targeting of Nanoparticles to Immune Cell Subsets via Cognate Antigen Interactions.

Within the body, cellular recognition is mediated in large part by receptor-ligand interactions that result from the surface marker expression of the participant cells. In the case of immune cells, these interactions can be highly specific, enabling them to carry out their protective functions in fighting off infection and malignancy. In this work, we demonstrate the biomimetic targeting of antigen-specific immune cell populations by using nanoparticles functionalized with natural membrane derived from cells expressing the cognate antigen.

Nanoparticulate Delivery of Cancer Cell Membrane Elicits Multiantigenic Antitumor Immunity.

Anticancer vaccines train the body's own immune system to recognize and eliminate malignant cells based on differential antigen expression. While conceptually attractive, clinical efficacy is lacking given several key challenges stemming from the similarities between cancerous and healthy tissue. Ideally, an effective vaccine formulation would deliver multiple tumor antigens in a fashion that potently stimulates endogenous immune responses against those antigens.

A Novel Biomimetic Nanosponge Protects the Retina from the Cytolysin.

Intraocular infections are a potentially blinding complication of common ocular surgeries and traumatic eye injuries. Bacterial toxins synthesized in the eye can damage intraocular tissue, often resulting in poor visual outcomes. causes blinding infections and is responsible for 8 to 17% of postoperative endophthalmitis cases.

Macrophage-like nanoparticles concurrently absorbing endotoxins and proinflammatory cytokines for sepsis management.

Sepsis, resulting from uncontrolled inflammatory responses to bacterial infections, continues to cause high morbidity and mortality worldwide. Currently, effective sepsis treatments are lacking in the clinic, and care remains primarily supportive. Here we report the development of macrophage biomimetic nanoparticles for the management of sepsis.

A Red Blood Cell Membrane-Camouflaged Nanoparticle Counteracts Streptolysin -Mediated Virulence Phenotypes of Invasive Group A .

Group A (GAS), an important human-specific Gram-positive bacterial pathogen, is associated with a broad spectrum of disease, ranging from mild superficial infections such as pharyngitis and impetigo, to serious invasive infections including necrotizing fasciitis and streptococcal toxic shock syndrome. The GAS pore-forming streptolysin O (SLO) is a well characterized virulence factor produced by nearly all GAS clinical isolates. High level expression of SLO is epidemiologically linked to intercontinental dissemination of hypervirulent clonotypes and poor clinical outcomes.

Erythrocyte-Platelet Hybrid Membrane Coating for Enhanced Nanoparticle Functionalization.

Cell-membrane-coated nanoparticles have recently been studied extensively for their biological compatibility, retention of cellular properties, and adaptability to a variety of therapeutic and imaging applications. This class of nanoparticles, which has been fabricated with a variety of cell membrane coatings, including those derived from red blood cells (RBCs), platelets, white blood cells, cancer cells, and bacteria, exhibit properties that are characteristic of the source cell. In this study, a new type of biological coating is created by fusing membrane material from two different cells, providing a facile method for further enhancing nanoparticle functionality.

Nanoparticles camouflaged in platelet membrane coating as an antibody decoy for the treatment of immune thrombocytopenia.

Immune thrombocytopenia purpura (ITP) is characterized by the production of pathological autoantibodies that cause reduction in platelet counts. The disease can have serious medical consequences, leading to uncontrolled bleeding that can be fatal. Current widely used therapies for the treatment of ITP are non-specific and can, at times, result in complications that are more burdensome than the disease itself.

Ultra-small lipid-polymer hybrid nanoparticles for tumor-penetrating drug delivery.

Lipid-polymer hybrid nanoparticles, consisting of a polymeric core coated by a layer of lipids, are a class of highly scalable, biodegradable nanocarriers that have shown great promise in drug delivery applications. Here, we demonstrate the facile synthesis of ultra-small, sub-25 nm lipid-polymer hybrid nanoparticles using an adapted nanoprecipitation approach and explore their utility for targeted delivery of a model chemotherapeutic. The fabrication process is first optimized to produce a monodisperse population of particles that are stable under physiological conditions.

Nanoparticle-Based Antivirulence Vaccine for the Management of Methicillin-Resistant Skin Infection.

With the rising threat of antibiotic-resistant bacteria, vaccination is becoming an increasingly important strategy to prevent and manage bacterial infections. Made from deactivated bacterial toxins, toxoid vaccines are widely used in the clinic as they help to combat the virulence mechanisms employed by different pathogens. Herein, the efficacy of a biomimetic nanoparticle-based anti-virulence vaccine is examined in a mouse model of methicillin-resistant (MRSA) skin infection.

Safe and Immunocompatible Nanocarriers Cloaked in RBC Membranes for Drug Delivery to Treat Solid Tumors.

The therapeutic potential of nanoparticle-based drug carriers depends largely on their ability to evade the host immune system while delivering their cargo safely to the site of action. Of particular interest are simple strategies for the functionalization of nanoparticle surfaces that are both inherently safe and can also bestow immunoevasive properties, allowing for extended blood circulation times. Here, we evaluated a recently reported cell membrane-coated nanoparticle platform as a drug delivery vehicle for the treatment of a murine model of lymphoma.

Coating nanofiber scaffolds with beta cell membrane to promote cell proliferation and function.

The cell membrane cloaking technique has emerged as an intriguing strategy in nanomaterial functionalization. Coating synthetic nanostructures with natural cell membranes bestows the nanostructures with unique cell surface antigens and functions. Previous studies have focused primarily on development of cell membrane-coated spherical nanoparticles and the uses thereof.

Nanoparticle biointerfacing by platelet membrane cloaking.

Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can affect nanoparticle effectiveness in complex, physiologically relevant systems. Despite the advances in bottom-up nanoengineering and surface chemistry, reductionist functionalization approaches remain inadequate in replicating the complex interfaces present in nature and cannot avoid exposure of foreign materials. Here we report on the preparation of polymeric nanoparticles enclosed in the plasma membrane of human platelets, which are a unique population of cellular fragments that adhere to a variety of disease-relevant substrates.

Cell membrane-camouflaged nanoparticles for drug delivery.

Nanoparticles can preferentially accumulate at sites of action and hold great promise to improve the therapeutic index of many drugs. While conventional methods of nanocarrier-mediated drug delivery have focused on primarily synthetic approaches, engineering strategies that combine synthetic nanoparticles with natural biomaterials have recently gained much attention. In particular, cell membrane-camouflaged nanoparticles are a new class of biomimetic nanoparticles that combine the unique functionalities of cellular membranes and engineering versatility of synthetic nanomaterials for effective delivery of therapeutic agents.

Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers.

Organophosphate poisoning is highly lethal as organophosphates, which are commonly found in insecticides and nerve agents, cause irreversible phosphorylation and inactivation of acetylcholinesterase (AChE), leading to neuromuscular disorders via accumulation of acetylcholine in the body. Direct interception of organophosphates in the systemic circulation thus provides a desirable strategy in treatment of the condition. Inspired by the presence of AChE on red blood cell (RBC) membranes, we explored a biomimetic nanoparticle consisting of a polymeric core surrounded by RBC membranes to serve as an anti-organophosphate agent.

Engineered nanoparticles mimicking cell membranes for toxin neutralization.

Protein toxins secreted from pathogenic bacteria and venomous animals rely on multiple mechanisms to overcome the cell membrane barrier to inflict their virulence effect. A promising therapeutic concept toward developing a broadly applicable anti-toxin platform is to administer cell membrane mimics as decoys to sequester these virulence factors. As such, lipid membrane-based nanoparticulates are an ideal candidate given their structural similarity to cellular membranes.

Modulating antibacterial immunity via bacterial membrane-coated nanoparticles.

Synthetic nanoparticles coated with cellular membranes have been increasingly explored to harness natural cell functions toward the development of novel therapeutic strategies. Herein, we report on a unique bacterial membrane-coated nanoparticle system as a new and exciting antibacterial vaccine. Using Escherichia coli as a model pathogen, we collect bacterial outer membrane vesicles (OMVs) and successfully coat them onto small gold nanoparticles (AuNPs) with a diameter of 30 nm.

Clearance of pathological antibodies using biomimetic nanoparticles.

Pathological antibodies have been demonstrated to play a key role in type II immune hypersensitivity reactions, resulting in the destruction of healthy tissues and leading to considerable morbidity for the patient. Unfortunately, current treatments present significant iatrogenic risk while still falling short for many patients in achieving clinical remission. In the present work, we explored the capability of target cell membrane-coated nanoparticles to abrogate the effect of pathological antibodies in an effort to minimize disease burden, without the need for drug-based immune suppression.

Current advances in polymer-based nanotheranostics for cancer treatment and diagnosis.

Nanotheranostics is a relatively new, fast-growing field that combines the advantages of treatment and diagnosis via a single nanoscale carrier. The ability to bundle both therapeutic and diagnostic capabilities into one package offers exciting prospects for the development of novel nanomedicine. Nanotheranostics can deliver treatment while simultaneously monitoring therapy response in real-time, thereby decreasing the potential of over- or under-dosing patients.

Cancer cell membrane-coated nanoparticles for anticancer vaccination and drug delivery.

Cell-derived nanoparticles have been garnering increased attention due to their ability to mimic many of the natural properties displayed by their source cells. This top-down engineering approach can be applied toward the development of novel therapeutic strategies owing to the unique interactions enabled through the retention of complex antigenic information. Herein, we report on the biological functionalization of polymeric nanoparticles with a layer of membrane coating derived from cancer cells.

Interfacial interactions between natural RBC membranes and synthetic polymeric nanoparticles.

The unique structural features and stealth properties of a recently developed red blood cell membrane-cloaked nanoparticle (RBC-NP) platform raise curiosity over the interfacial interactions between natural cellular membranes and polymeric nanoparticle substrates. Herein, several interfacial aspects of the RBC-NPs are examined, including completeness of membrane coverage, membrane sidedness upon coating, and the effects of polymeric particles' surface charge and surface curvature on the membrane cloaking process. The study shows that RBC membranes completely cover negatively charged polymeric nanoparticles in a right-side-out manner and enhance the particles' colloidal stability.

Nanoparticle-detained toxins for safe and effective vaccination.

Toxoid vaccines--vaccines based on inactivated bacterial toxins--are routinely used to promote antitoxin immunity for the treatment and prevention of bacterial infections. Following chemical or heat denaturation, inactivated toxins can be administered to mount toxin-specific immune responses. However, retaining faithful antigenic presentation while removing toxin virulence remains a major challenge and presents a trade-off between efficacy and safety in toxoid development.