Gloria Kim

For the last three decades, the concept of immunoediting has evolved to characterize our increasing understanding of the interactions between cells from the immune system and cancer development. Elucidating the role of immune cells in the progression of cancer has been very challenging due to their dual role; the immune system can either suppress tumor formation by killing cancer cells, or it can also promote tumor growth. Revealing how immune cells are hampered by the tumor microenvironment and how they aid tumor progression has signaled strategies to reverse these effects and control cancer cell growth; this has been the advent of immunotherapy design. More recently, the role of physical forces in the process of immunoediting has been highlighted by multiple studies focusing on understanding how force changes in the stiffness of the extracellular matrix and fluid flow shear stress contribute to tumor development. Using models in vitro that incorporate biomechanical components, it ...

The mandate of folic acid supplementation in grained products has reduced the occurrence of neural tube defects by one third in the U.S since its introduction by the Food and Drug Administration in 1998. However, the advantages and possible mechanisms of action of using folic acid for peripheral nerve engineering and neurological diseases still remain largely elusive. Herein, folic acid is described as an inexpensive and multifunctional niche component that modulates behaviors in different cells in the nervous system. The multiple benefits of modulation include: 1) generating chemotactic responses on glial cells, 2) inducing neurotrophin release, and 3) stimulating neuronal differentiation of a PC-12 cell system. For the first time, folic acid is also shown to enhance cellular force generation and global methylation in the PC-12 cells, thereby enabling both biomechanical and biochemical pathways to regulate neuron differentiation. These findings are evaluated in vivo for clinical tr...

Implanting fiber optical waveguides into tissue or organs for light delivery and collection is among the most effective ways to overcome the issue of tissue turbidity, a long-standing obstacle for biomedical optical technologies. Here, we report a citrate-based material platform with engineerable opto-mechano-biological properties and demonstrate a new type of biodegradable, biocompatible, and low-loss step-index optical fiber for organ-scale light delivery and collection. By leveraging the rich designability and processibility of citrate-based biodegradable polymers, two exemplary biodegradable elastomers with a fine refractive index difference and yet matched mechanical properties and biodegradation profiles were developed. Furthermore, we developed a two-step fabrication method to fabricate flexible and low-loss (0.4 db/cm) optical fibers, and performed systematic characterizations to study optical, spectroscopic, mechanical, and biodegradable properties. In addition, we demonstr...

Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell-mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic applications. By taking advantage of innate immune cell's ability to target tumor cells, the authors develop a novel drug delivery system by using macrophages as both nanoparticle (NP) carriers and navigators to achieve cancer-specific drug delivery. Theranostic NPs are fabricated from a unique polymer, biodegradable photoluminescent poly (lactic acid) (BPLP-PLA), which possesses strong fluorescence, biodegradability, and cytocompatibility. In order to minimize the toxicity of cancer drugs to immune cells and other healthy cells, an anti-BRAF V600E mutant melanoma specific drug (PLX4032) is loaded into BPLP-PLA nanoparticles. Muramyl tripeptide is also con...

For the first time, a convenient copper-catalyzed azide-alkyne cycloaddition (CuAAC, click chemistry) was successfully introduced into injectable citrate-based mussel-inspired bioadhesives (iCMBAs, iCs) to improve both cohesive and wet adhesive strengths and elongate the degradation time, providing numerous advantages in surgical applications. The major challenge in developing such adhesives was the mutual inhibition effect between the oxidant used for crosslinking catechol groups and the Cu(II) reductant used for CuAAC, which was successfully minimized by adding a biocompatible buffering agent typically used in cell culture, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), as a copper chelating agent. Among the investigated formulations, the highest adhesion strength achieved (223.11 ± 15.94 kPa) was around 13 times higher than that of a commercially available fibrin glue (15.4 ± 2.8 kPa). In addition, dual-crosslinked (i.e. click crosslinking and mussel-inspired crossli...

A simultaneously photo-cleavable and activatable prodrug-backboned block copolymer (BCP) micelle strategy is demonstrated. Without light treatment, the micelles stay silent and inactivated, being biocompatible to normal tissues. Concurrent chain cleavage of BCP micelles and the activation of Pt(IV) prodrug could be temporally and spatially triggered by UV or even visible light for precise anticancer drug delivery.

ABSTRACT Advances in nanotechnology have generated wide interest in applying nanomaterials for neural prostheses. On page 1846, M. R. Abidian and co-workers provide an overview of state-of-the-art neural electrodes and advancements in electroactive nanomaterials including conducting polymers, carbon nanotubes, graphene, silicon nanowires, and hybrid organic-inorganic nanomaterials for neural interfaces. They discuss scientific challenges in biocompatibility, mechanical mismatch, and electrical properties faced by these nanomaterials for the development of longlasting functional neural interfaces.

The purpose of this study is to establish a modeling approach that can be used to predict bulk powder flowability of pharmaceutical materials from their particle size and shape distributions. To build and validate the model, 23 commonly used pharmaceutical excipients and 38 binary blends were fully characterized for their particle size and shape distributions. The particle size and shape of each sample was characterized by multiple descriptors to fully reflect their morphological characteristics. The flow properties of these materials were analyzed using the Schulze Ring Shear Tester at a fixed humidity condition. A partial least squares (PLS) approach was used to build the mathematical model. Several different modeling approaches were attempted and the best method was identified as using a combination of formulation composition and particle size and shape distributions of single-component powder systems. The PLS model was shown to provide excellent predictions of powder flow function coefficient (FFC) of up to approximately 20. The results also revealed that both particle size and shape play an important role in determining the powder flow behavior.

Drug delivery systems, particularly nanomaterialbased
drug delivery systems, possess a tremendous amount of
potential to improve the diagnostic and therapeutic effects of
drugs. Controlled drug delivery targeted to a specific disease is
designed to significantly improve the pharmaceutical effects of
drugs and reduce their side effects. Unfortunately, only a few
targeted drug delivery systems can achieve high targeting
efficiency after intravenous injection, even with the development
of numerous surface markers and targeting modalities. Thus,
alternative drug and nanomedicine targeting approaches are
desired. Circulating cells, such as erythrocytes, leukocytes, and stem cells, present innate disease sensing and homing properties.
Hence, using living cells as drug delivery carriers has gained increasing interest in recent years. This review highlights the recent
advances in the design of cell-mediated drug delivery systems and targeting mechanisms. The approaches of drug encapsulation/
conjugation to cell carriers, cell-mediated targeting mechanisms, and the methods of controlled drug release are elaborated here.
Cell-based “live” targeting and delivery could be used to facilitate a more specific, robust, and smart payload distribution for the
next-generation drug delivery systems.