Organelle-Targeting Nanoparticles.

Organelles are specialized subunits within cells which carry out vital functions crucial to cellular survival and form a tightly regulated network. Dysfunctions in any of these organelles are linked to numerous diseases impacting virtually every organ system in the human body. Targeted delivery of therapeutics to specific organelles within the cell holds great promise for overcoming challenging diseases and improving treatment outcomes through the minimization of therapeutic dosage and off-target effects.

The role of patient-specific variables in protein corona formation and therapeutic efficacy in nanomedicine.

Despite their potential, the adoption of nanotechnology in therapeutics remains limited, with only around eighty nanomedicines approved in the past 30 years. This disparity is partly due to the "one-size-fits-all" approach in medical design, which often overlooks patient-specific variables such as biological sex, genetic ancestry, disease state, environment, and age that influence nanoparticle behavior. Nanoparticles (NPs) must be transported through systemic, microenvironmental, and cellular barriers that vary across heterogeneous patient populations.

Paracellular Delivery of Protein Drugs with Smart EnteroPatho Nanoparticles.

A general platform for the safe and effective oral delivery of biologics would revolutionize the administration of protein-based drugs, improving access for patients and lowering the financial burden on the health-care industry. Because of their dimensions and physiochemical properties, nanomaterials stand as promising vehicles for navigating the complex and challenging environment in the gastrointestinal (GI) tract. Recent developments have led to materials that protect protein drugs from degradation and enable controlled release in the small intestine, the site of absorption for most proteins.

siRNA Delivery from Cationic Nanocarriers Prepared by Diffusion-assisted Loading in the Presence and Absence of Electrostatic Interactions.

In this study, we use modified cationic nanocarriers as vehicles for the intracellular delivery of therapeutic siRNA. After developing nanocarrier formulations with appropriate pK, size, swellability, and cytocompatibility, we investigated the importance of siRNA loading methods by studying the impact of the pH and time over which siRNA is loaded into the nanocarriers. We concentrate on diffusion-based loading in the presence and absence of electrostatic interactions.

Supramolecular artificial Nano-AUTACs enable tumor-specific metabolism protein degradation for synergistic immunotherapy.

Autophagy-targeting chimera (AUTAC) has emerged as a powerful modality that can selectively degrade tumor-related pathogenic proteins, but its low bioavailability and nonspecific distribution significantly restrict their therapeutic efficacy. Inspired by the guanine structure of AUTAC molecules, we here report supramolecular artificial Nano-AUTACs (GM NPs) engineered by AUTAC molecule GN [an indoleamine 2,3-dioxygenase (IDO) degrader] and nucleoside analog methotrexate (MTX) through supramolecular interactions for tumor-specific protein degradation. Their nanostructures allow for precise localization and delivery into cancer cells, where the intracellular acidic environment can disrupt the supramolecular interactions to release MTX for eradicating tumor cells, modulating tumor-associated macrophages, activating dendritic cells, and inducing autophagy.

Near-infrared light-responsive hydrogels for on-demand dual delivery of proangiogenic growth factors.

Achieving precise spatiotemporal control over the release of proangiogenic factors is crucial for vasculogenesis, the process of de novo blood vessel formation. Although various strategies have been explored, there is still a need to develop cell-laden biomaterials with finely controlled release of proangiogenic factors at specific locations and time points. We report on the developed of a near-infrared (NIR) light-responsive collagen hydrogel comprised of gold nanorods (GNRs)-conjugated liposomes containing proangiogenic growth factors (GFs).

Therapeutic delivery systems for rheumatoid arthritis based on hydrogel carriers.

Rheumatoid arthritis (RA) is an autoimmune disease suffered by millions of people worldwide. It can significantly affect the patient's quality of life by damaging not only the joints but also organs such as the lungs and the heart. RA is normally treated using nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-modifying antirheumatic drugs (DMARDs), and biologics.

A highly tuneable inverse emulsion polymerization for the synthesis of stimuli-responsive nanoparticles for biomedical applications.

Polymeric nanomaterials have seen widespread use in biomedical applications as they are highly tuneable to achieve the desired stimuli-responsiveness, targeting, biocompatibility, and degradation needed for fields such as drug delivery and biosensing. However, adjustments to composition and the introduction of new monomers often necessitate reoptimization of the polymer synthesis to achieve the target parameters. In this study, we explored the use of inverse emulsion polymerization to prepare a library of polymeric nanoparticles with variations in pH and temperature response and examined the impact of overall batch volume and the volume of the aqueous phase on nanoparticle size and composition.

Design of nanoparticle-based systems for the systemic delivery of chemotherapeutics: Alternative potential routes via sublingual and buccal administration for systemic drug delivery.

Conventional therapeutic approaches for cancer generally involve chemo- and radiation therapies that often exhibit low efficacy and induce toxic side effects. Recent years have seen significant advancements in the use of protein biologics as a promising alternative treatment option. Nanotechnology-based systems have shown great potential in providing more specific and targeted cancer treatments, thus improving upon many of the limitations associated with current treatments.

PEGylated insulin loaded complexation hydrogels for protected oral delivery.

While a number of enteric coatings and pH-sensitive oral delivery vehicles have been developed, they lack the ability to sufficiently protect proteins from proteolytic degradation once released from the carrier. In this work, we show that H-bonded, pH-sensitive poly(methacrylic acid-grafted ethylene glycol) glycol (henceforth designated as P(MAA-g-EG) gels) exhibit great promise as protein carriers, as they utilize poly(ethylene glycol) (PEG) chains to promote mucoadhesion in the small intestine, increasing the chances that the drug is released within the villus of the absorptive intestinal wall. Importantly, PEG was also conjugated to the B29-lysine (LysB29) position of insulin in order to protect the drug from proteolytic degradation once released in the small intestine and adhere the drug to the intestinal epithelium through improved mucoadhesion.

Reversible, Covalent DNA Condensation Approach Using Chemical Linkers for Enhanced Gene Delivery.

Nonviral gene delivery has emerged as a promising technology for gene therapy. Nonetheless, these approaches often face challenges, primarily associated with lower efficiency, which can be attributed to the inefficient transportation of DNA into the nucleus. Here, we report a two-stage condensation approach to achieve efficient nuclear transport of DNA.

Two-phase matrices for the controlled release of therapeutic proteins.

Controlled and sustained delivery of therapeutic proteins is crucial for achieving desired effects in wound healing applications. Yet, this remains a challenge in growth factor delivery for bone tissue engineering. Current delivery systems can lead to negative side effects, such as ectopic bone growth and cancer, due to the over administration of growth inducing proteins.

Drug delivery methods for cancer immunotherapy.

Despite the fact that numerous immunotherapy-based drugs have been approved by the FDA for the treatment of primary and metastatic tumors, only a small proportion of the population can benefit from them because of primary and acquired resistances. Moreover, the translation of immunotherapy from the bench to the clinical practice is being challenging because of the short half-lives of the involved molecules, the difficulties to accomplish their delivery to the target sites, and some serious adverse effects that are being associated with these approaches. The emergence of drug delivery vehicles in the field of immunotherapy is helping to overcome these difficulties and limitations and this review describes how, providing some illustrative examples.

Structurally decoupled stiffness and solute transport in multi-arm poly(ethylene glycol) hydrogels.

Synthetic hydrogels are widely used as artificial 3D environments for cell culture, facilitating the controlled study of cell-environment interactions. However, most hydrogels are limited in their ability to represent the physical properties of biological tissues because stiffness and solute transport properties in hydrogels are closely correlated. Resultingly, experimental investigations of cell-environment interactions in hydrogels are confounded by simultaneous changes in multiple physical properties.

Stimuli-responsive self-assembled polymer nanoparticles for the oral delivery of antibodies.

Currently, commercially available antibody therapies must be delivered via parenteral administration. Oral delivery of antibodies could increase patient compliance and improve quality of life, however there is currently no viable system for delivering antibodies orally. In this work, a self-assembled, pH-responsive nanoparticle delivery system was developed to load and deliver antibodies via the oral route.

Targeted delivery methods for RNA interference are necessary to obtain a potential functional cure for HIV/AIDS.

Ribonucleic acid (RNA) is of great interest in many different therapeutic areas including infectious diseases such as immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Thanks to current, advanced treatments for HIV, the diagnosis is no longer a death sentence. However, even with these treatments, latency is suggested to persist in T-lymphocyte-rich tissues including gut-associated lymphatic tissue (GALT), spleen, and bone marrow making HIV an incurable disease.

Self-assembled block copolymer biomaterials for oral delivery of protein therapeutics.

Protein therapeutics have guided a transformation in disease treatment for various clinical conditions. They have been successful in numerous applications, but administration of protein therapeutics has been limited to parenteral routes which can decrease patient compliance as they are invasive and painful. In recent years, the synergistic relationship of novel biomaterials with modern protein therapeutics has been crucial in the treatment of diseases that were once thought of as incurable.

Design of Synthetic Hydrogel Compositions for Noncovalent Protein Recognition.

Multifunctional hydrogels composed of segments with ionizable, hydrophilic, and hydrophobic monomers have been optimized for sensing, bioseparation, and therapeutic applications. While the "biological identity" of bound proteins from biofluids underlies device performance in each context, design rules that predict protein binding outcomes from hydrogel design parameters are lacking. Uniquely, hydrogel designs that influence protein affinity (e.

Solute diffusion and partitioning in multi-arm poly(ethylene glycol) hydrogels.

Controlling solute transport in hydrogels is critical for numerous chemical separation applications, tissue engineering, and drug delivery systems. In previous review work, we have pointed out that proposed theoretical models and associated experiments tend to oversimplify the influence of the hydrogel structure on solute transport by addressing only the effects of the polymer volume fraction and mesh size of the networks on solute transport. Here, we reexamine these models by experimenting with a library of multi-arm poly(ethylene glycol) (PEG) hydrogels with simultaneous variations in four independent structural parameters.

Hydrogel-guided strategies to stimulate an effective immune response for vaccine-based cancer immunotherapy.

Cancer vaccines have attracted widespread interest in tumor therapy because of the potential to induce an effective antitumor immune response. However, many challenges including weak immunogenicity, off-target effects, and immunosuppressive microenvironments have prevented their broad clinical translation. To overcome these difficulties, effective delivery systems have been designed for cancer vaccines.

Immunotherapy approaches for hematological cancers.

Hematological cancers such as leukemia, lymphoma, and multiple myeloma have traditionally been treated with chemo and radiotherapy approaches. Introduction of immunotherapies for treatment of these diseases has led to patient remissions that would not have been possible with traditional approaches. In this critical review we identify main disease characteristics, symptoms, and current treatment options.

Recent advances in glucose-responsive insulin delivery systems: novel hydrogels and future applications.

Over the past several decades, there have been major advancements in the field of glucose sensing and insulin delivery for the treatment of type I diabetes mellitus. The introduction of closed-loop insulin delivery systems that deliver insulin in response to specific levels of glucose in the blood has shifted significantly the research in this field. These systems consist of encapsulated glucose-sensitive components such as glucose oxidase or phenylboronic acid in hydrogels, microgels or nanoparticles.

High-Throughput FRAP Analysis of Solute Diffusion in Hydrogels.

Increasingly accurate mathematical models have been developed to relate solute and hydrogel properties to solute diffusion coefficients in hydrogels, primarily by comparing solute sizes and hydrogel mesh sizes. Here, we use a standardized, high-throughput method for fluorescence recovery after photobleaching (FRAP) experiments and analysis to characterize the diffusion coefficients of fluorescein, three sizes of FITC-dextran, and three sizes of FITC-conjugated poly(ethylene glycol) (PEG) through 18 structurally varied poly(vinyl alcohol) (PVA) hydrogel formulations. Increasing the hydrogel mesh radii increased the diffusivities of all the tested solutes within the hydrogels.