Hunter N. Bomba

Anticancer Platelet-Mimicking Nanovehicles.

A core-shell nanovehicle coated with a platelet membrane (PM) is developed for targeted and site-specific delivery of an extracellularly active drug and an intracellular functional small-molecular drug, leading to enhanced antitumor efficacy. This PM-coated nanovehicle can also effectively eliminate the circulating tumor cells in vivo and inhibit development of tumor metastasis.

Engineered Nanoplatelets for Enhanced Treatment of Multiple Myeloma and Thrombus

A platelet-membrane-coated biomimetic nanocarrier, which can sequentially target the bone microenvironment and myeloma cells to enhance the drug availability at the myeloma site and decrease off-target effects, is developed for inhibiting multiple myeloma growth and simultaneously eradicating thrombus complication.

In situ formed reactive oxygen species–responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy

A ROS-responsive hydrogel scaffold controls release of gemcitabine and immune checkpoint inhibitor for enhanced antitumor activity. An antitumor two-step Although cancer immunotherapy can be quite effective, it has a variety of drawbacks. Most patients still do not achieve remission, whereas those who respond to therapy often experience immune-related side effects. Wang et al. address both of these concerns by maximizing drug access to tumors and minimizing systemic exposure. To achieve this, the authors designed a hydrogel that they inject at the site of a tumor, where it forms a scaffold for sequential release of drugs. A cytotoxic chemotherapy is released first, killing some cancer cells before the release of most of an immune checkpoint inhibitor, which then stimulates antitumor immunity. With this approach, the authors demonstrate efficacy in mouse models of primary tumors, as well as those that recur after surgery. Patients with low-immunogenic tumors respond poorly to immune checkpoint blockade (ICB) targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. Conversely, patients responding to ICB can experience various side effects. We have thus engineered a therapeutic scaffold that, when formed in situ, allows the local release of gemcitabine (GEM) and an anti–PD-L1 blocking antibody (aPDL1) with distinct release kinetics. The scaffold consists of reactive oxygen species (ROS)–degradable hydrogel that releases therapeutics in a programmed manner within the tumor microenvironment (TME), which contains abundant ROS. We found that the aPDL1-GEM scaffold elicits an immunogenic tumor phenotype and promotes an immune-mediated tumor regression in the tumor-bearing mice, with prevention of tumor recurrence after primary resection.

Stimuli‐responsive delivery of therapeutics for diabetes treatment

Abstract Diabetic therapeutics, including insulin and glucagon‐like peptide 1 (GLP‐1), are essential for diabetic patients to regulate blood glucose levels. However, conventional treatments that are based on subcutaneous injections are often associated with poor glucose control and a lack of patient compliance. In this review, we focus on the different stimuli‐responsive systems to deliver therapeutics for diabetes treatment to improve patient comfort and prevent complications. Specifically, the pH‐responsive systems for oral drug delivery are introduced first. Then, the closed‐loop glucose‐responsive systems are summarized based on different glucose‐responsive moieties, including glucose oxidase, glucose binding protein, and phenylboronic acid. Finally, the on‐demand delivery systems activated by external remote triggers are also discussed. We conclude by discussing advantages and limitations of current strategies, as well as future opportunities and challenges in this area.

Engineering platelet-mimicking drug delivery vehicles

Platelets dynamically participate in various physiological processes, including wound repair, bacterial clearance, immune response, and tumor metastasis. Recreating the specific biological features of platelets by mimicking the structure of the platelet or translocating the platelet membrane to synthetic particles holds great promise in disease treatment. This review highlights recent advancements made in the platelet-mimicking strategies. The future opportunities and translational challenges are also discussed.

Bioengineering of Artificial Antigen Presenting Cells and Lymphoid Organs

The immune system protects the body against a wide range of infectious diseases and cancer by leveraging the efficiency of immune cells and lymphoid organs. Over the past decade, immune cell/organ therapies based on the manipulation, infusion, and implantation of autologous or allogeneic immune cells/organs into patients have been widely tested and have made great progress in clinical applications. Despite these advances, therapy with natural immune cells or lymphoid organs is relatively expensive and time-consuming. Alternatively, biomimetic materials and strategies have been applied to develop artificial immune cells and lymphoid organs, which have attracted considerable attentions. In this review, we survey the latest studies on engineering biomimetic materials for immunotherapy, focusing on the perspectives of bioengineering artificial antigen presenting cells and lymphoid organs. The opportunities and challenges of this field are also discussed.

Nanomedicine: Anticancer Platelet‐Mimicking Nanovehicles (Adv. Mater. 44/2015)

The inside front cover is a schematic representation of an anticancer platelet-mimicking drug-delivery system described by Z. Gu and co-workers on page 7043. The platelet membrane-coated nanovehicles can inhibit primary tumor growth, and also eliminate circulating tumor cells through sequential delivery of plasma membrane-associated cytokine and intracellularly functional small-molecule drugs.