Venomous bites and stings from animals such as snake, spider, scorpion, and various insects are serious threats to personnel in areas associated with increased risk of venomous injuries. Such envenomation can cause life-threatening symptoms including paralysis, bleeding disorders, organ failures, and shock. Current treatments of venomous bites are primarily based on antiserum, which is blood serum containing polyclonal antibodies raised against specific venom types in animals. Such antivenom solutions are difficult to administer, as the structure-specific antiserum requires clear identification of the venom type. In addition, the xenotypic nature of antiserum is associated with adverse complications, such as serum sickness and hypersensitivity. Administrations of these serum-based antivenoms typically require the patient to be closely monitored in medical facilities. In addition, antivenoms based on species-specific immune reaction to venom exposure are also difficult and costly to manufacture; few formulations have received approval by the Food and Drug Administration (FDA).
Schematic representation of an antivenom nanosponge, which possesses nanoparticle-supported red blood cell membranes to absorb and neutralize membrane-active venomous proteins.
Nanosponges represent a novel antivenom treatment with broad applicability. Animal venoms are highly heterogenous in composition and venomous injuries often involve simultaneous effects from a diverse population of toxins. The large diversity of toxin structures makes it unrealistic to develop broadly applicable antivenom solutions based on conventional structure-specific neutralization mechanisms. In contrast to traditional antivenom strategies, nanosponges feature a mechanism-targeted detoxification based on cell-mimicking nanoparticles. Owing to their biomimetic nature, the nanosponges are capable of interacting with membrane-active venomous proteins similarly to the natural toxin/membrane interactions. Upon toxin interaction, the particle-stabilized cell membranes can restrain the toxin’s freedom and preclude it from interacting with other cell membrane targets. Since membrane interaction and disruption is a common virulence mechanism in many venomous proteins, the nanosponge platform presents a compelling antivenom platform that can be applied to a variety of venomous injuries.
The nanosponges were demonstrated to retain the surface properties of RBCs and readily absorb multiple membrane-active hemolytic toxins. The nanosponges also possess anti-phagocytic properties and do not elicit complement activations owing to their biocompatible exterior. In a mouse model, nanosponges prepared from mouse RBCs can circulate for an extended period of time (40 hr elimination half-life) given their immune-evasive nature. Nanosponges can be prepared from type O rhesus negative RBCs (O-RBCs), which are known as universal donor RBCs given their lack of major blood group antigens for immune rejection. These nanosponges are broadly compatible and do not elicit the activation of the classical complement activation. Such compatibility attests to nanosponge safety. Nanosponges retain anti-toxin activity upon lyophilization and subsequent reconstitution, which provides a feasible method for storing the formulation toward practical usage.