The design of next-generation nanobiomaterials requires precise engineering of both physical properties of the core material and chemical properties of the material’s surface to meet a biological function. A bio-inspired modular and versatile technology was developed to allow biodegradable polymeric nanoparticles to circulate through the blood for extended periods of time while also acting as a detoxification device. To mimic red blood cells, physical and chemical biomimicry are combined to enhance the biological function of nanomaterials in vitro and in vivo. The anisotropic shape and membrane coating synergize to resist cellular uptake and reduce clearance from the blood. This approach enhances the detoxification properties of nanoparticles, markedly improving survival in a mouse model of sepsis. The anisotropic membrane-coated nanoparticles have enhanced biodistribution and therapeutic efficacy. These biomimetic biodegradable nanodevices and their derivatives have promise for applications ranging from detoxification agents, to drug delivery vehicles, and to biological sensors.

Targeted, noninvasive neuromodulation of the brain of an otherwise awake subject could revolutionize both basic and clinical neuroscience. Toward this goal, we have developed nanoparticles that allow noninvasive uncaging of a neuromodulatory drug, in this case the small molecule anesthetic propofol, upon the application of focused ultrasound. These nanoparticles are composed of biodegradable and biocompatible constituents and are activated using sonication parameters that are readily achievable by current clinical transcranial focused ultrasound systems. These particles are potent enough that their activation can silence seizures in an acute rat seizure model. Notably, there is no evidence of brain parenchymal damage or blood-brain barrier opening with their use. Further development of these particles promises noninvasive, focal, and image-guided clinical neuromodulation along a variety of pharmacological axes.

Non‐spherical nanodimensional artificial antigen presenting cells (naAPCs) offer the potential to systemically induce an effective antigen‐specific immune response. In this report it is shown biodegradable ellipsoidal naAPCs mimic the T‐Cell/APC interaction better than equivalent spherical naAPCs. In addition, it is demonstrated ellipsoidal naAPCs offer reduced non‐specific cellular uptake and a superior pharmacokinetic profile compared to spherical naAPCs.

Biomimetic materials that target the immune system and generate an anti-tumor responses hold promise in augmenting cancer immunotherapy. These synthetic materials can be engineered and optimized for their biodegradability, physical parameters such as shape and size, and controlled release of immune-modulators. As these new platforms enter the playing field, it is imperative to understand their interaction with existing immunotherapies since single-targeted approaches have limited efficacy. Here, we investigate the synergy between a PLGA-based artificial antigen presenting cell (aAPC) and a checkpoint blockade molecule, anti-PD1 monoclonal antibody (mAb). The combination of antigen-specific aAPC-based activation and anti-PD-1 mAb checkpoint blockade induced the greatest IFN-γ secretion by CD8+ T cells in vitro. Combination treatment also acted synergistically in an in vivo murine melanoma model to result in delayed tumor growth and extended survival, while either treatment alone had no effect. This was shown mechanistically to be due to decreased PD-1 expression and increased antigen-specific proliferation of CD8+ T cells within the tumor microenvironment and spleen. Thus, biomaterial-based therapy can synergize with other immunotherapies and motivates the translation of biomimetic combinatorial treatments.

Nanofabrication and biomedical applications of polymeric nanoparticles have become important areas of research. Biocompatible polymeric nanoparticles have been investigated for their use as delivery vehicles for therapeutic and diagnostic agents. Although polymeric nanoconstructs have traditionally been fabricated as isotropic spheres, anisotropic, non-spherical nanoparticles have gained interest in the biomaterials community due to their unique interactions with biological systems. Polymeric nanoparticles with different forms of anisotropy have been manufactured utilizing a variety of novel methods in recent years. In addition, they have enhanced physical, chemical, and biological properties compared to spherical nanoparticles, including increased targeting avidity and decreased non-specific in vivo clearance. With these desirable properties, anisotropic nanoparticles have been successfully utilized in many biomedical settings and have performed superiorly to analogous spherical nanoparticles. We summarize the current state-of-the-art fabrication methods for anisotropic polymeric nanoparticles including top-down, bottom-up, and microfluidic design approaches. We also summarize the current and potential future applications of these nanoparticles, including drug delivery, biological targeting, immunoengineering, and tissue engineering. Ongoing research into the properties and utility of anisotropic polymeric nanoparticles will prove critical to realizing their potential in nanomedicine.

In recent years, there have been major advances in the development of novel nanoparticle and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health.

New advances in biomaterial-based approaches to modulate the immune system are being applied to treat cancer, infectious diseases, and autoimmunity. Particulate systems are especially well-suited to deliver immunomodulatory factors to immune cells since their small size allows them to engage cell surface receptors or deliver cargo intracellularly after internalization. Biodegradable polymeric particles are a particularly versatile platform for the delivery of signals to the immune system because they can be easily surface-modified to target specific receptors and engineered to release encapsulated cargo in a precise, sustained manner. Micro- and nanoscale systems have been used to deliver a variety of therapeutic agents including monoclonal antibodies, peptides, and small molecule drugs that function to activate the immune system against cancer or infectious disease, or suppress the immune system to combat autoimmune diseases and transplant rejection. This review provides an overview of recent advances in the development of polymeric micro- and nanoparticulate systems for the presentation and delivery of immunomodulatory agents targeted to a variety of immune cell types including APCs, T cells, B cells, and NK cells.

Triggering shape-memory functionality under clinical hyperthermia temperatures could enable the control and actuation of shape-memory systems in clinical practice. For this purpose, we developed light-inducible shape-memory microparticles composed of a poly(d,l-lactic acid) (PDLLA) matrix encapsulating gold nanoparticles (Au@PDLLA hybrid microparticles). This shape-memory polymeric system for the first time demonstrates the capability of maintaining an anisotropic shape at body temperature with triggered shape-memory effect back to a spherical shape at a narrow temperature range above body temperature with a proper shape recovery speed (37 < T < 45 °C). We applied a modified film-stretching processing method with carefully controlled stretching temperature to enable shape memory and anisotropy in these micron-sized particles. Accordingly, we achieved purely entanglement-based shape-memory response without chemical cross-links in the miniaturized shape-memory system. Furthermore, these shape-memory microparticles exhibited light-induced spatiotemporal control of their shape recovery using a laser to trigger the photothermal heating of doped gold nanoparticles. This shape-memory system is composed of biocompatible components and exhibits spatiotemporal controllability of its properties, demonstrating a potential for various biomedical applications, such as tuning macrophage phagocytosis as demonstrated in this study.