Dong June Ahn

3D cellular models have been increasingly integrated into the drug development process, but maintaining their functional integrity over extended periods remains a major barrier to clinical translation and commercialization. Cryopreservation represents a key strategy for enabling long‐term storage of intact 3D cellular systems; however, the limited diffusion of conventional agents into densely organized structures often compromises post‐thaw recovery. We introduce a colloidal solution containing nanoscale peptide‐colloid hybrids designed to preferentially interact with the extracellular matrix. This solution infiltrated spheroids and distributed homogenously through 3D spheroidal space, which outperformed conventional cryoprotectants in preserving post‐thaw structural integrity and functional activity. At sub‐picomolar colloidal concentration, the solution leverages a synergetic Gibbs effect to generate an ice‐melting thermodynamic efficiency comparable to high‐concentration colligative dimethyl sulfoxide (DMSO). Remarkably, the colloid nanoparticles can be readily removed from the spheroids with a single step of post‐thaw rinsing, mitigating the risks associated with residual cytotoxicity.

Curcumin offers significant therapeutic potential but is hindered by poor aqueous stability and limited cellular accessibility. Here, we present a curcumin nanotherapeutic platform featuring OH-rich, silanol-rich porous silica nanointerfaces (CU@silica NPs) that successfully decouple structural stabilization from molecular mobility. By employing poly(allylamine hydrochloride) (PAH)-assisted assembly and rapid tetramethyl orthosilicate (TMOS) hydrolysis, we engineered a mesostructured silica shell with a high density of surface silanol groups, creating diffusion pathways that preserve curcumin mobility while protecting it from degradation. This permeable nanointerface enables lipid-triggered fluorescence activation, allowing activation-responsive monitoring of drug delivery. The OH-rich silica interface further ensures exceptional redispersibility and functional preservation even after repeated powderization cycles, a critical requirement for long-term storage and transport. Supported by molecular dynamics simulations and in vitro evaluations, CU@silica NPs demonstrate accelerated cellular uptake and a five-fold improvement in anticancer efficacy compared with CU NPs. These findings establish silica nano-interface engineering as a robust strategy for developing storage-stable, stimuli-responsive, and image-guided nanomedicines for hydrophobic drugs.

Nanoscale architecture alone does not guarantee effective ice recrystallization inhibition (IRI). The strong IRI activity of tyrosine monomer nanocrystals highlights the importance of chemical functionality, crystallinity, and colloidal stability.

Current imaging techniques suffer from a lack of specificity and resolution, leading to inaccurate tumor imaging and limited applicability of targeted contrast agents, as they require cancer‐specific development. The need for enhanced contrast through improved tumor‐to‐background ratio (TBR) and the toxicity from repeated injections due to fading fluorescent signals further complicate the issue. Additionally, challenges in visualizing the entire 3D tumor with surface‐stained contrast agents highlight the demand for advanced imaging solutions for more precise surgical guidance. A novel approach is proposed utilizing Streptavidin Associated Salmonella (SAS) as a contrast agent for image‐guided surgeries. SAS selectively proliferates in cancerous tissues and secretes streptavidin upon induction, enabling the binding of subsequently injected biotin‐conjugated fluorescent dyes. This approach enhances tumor visualization with a TBR of up to 15.3, far surpassing conventional agents (TBR ∼ 2), while enabling prolonged 3‐day imaging, deep tumor penetration, and precise invasive margin delineation with a single contrast agent injection. Furthermore, biosafety evaluations confirmed efficient bacterial clearance, absence of systemic toxicity, and stable physiological responses, supporting its potential for safe clinical translation. This innovative method offers substantial improvements over existing fluorescent contrast agents and holds promise for both diagnostic and therapeutic applications in cancer surgery.

Micrometer-scale polarized polymeric rectangles with nanometer-scale thicknesses were fabricated through the simple reprecipitation of selected diacetylenic surfactants, exhibiting anisotropic responses to directional external fields. These 2D rectangular plates feature linearly conjugated poly(diacetylene) backbones aligned along their shorter side over large domains, enabling unique angle-dependent polarization of visible light and fluorescent emission. The conformity to Malus's law confirms the reliability of the linear polarization demonstrated by these plates. In addition to optical anisotropy, these polymer rectangles exhibit an orientation-dependent mechanical response. When tensile force is applied parallel to the shorter side or polymer backbone, the plates undergo a distinct visual color transition; however, little to no change occurs when the force is applied perpendicularly. Such an anisotropic response behavior of 2D rectangular plates is further validated by molecular dynamics simulations. This work provides a strategic framework for materials chemistry design that enables optical reflection of orientation-dependent external fields.

Cascade enzymatic reactions in living organisms are fundamental reaction mechanisms in coordinating various complex biochemical processes such as metabolism, signal transduction, and gene regulation. Many studies have attempted to mimic cascade reactions using nanoparticles with enzyme-like activity; however, precisely tuning each reaction within complex networks to enhance the catalytic activity remains challenging. Here, we present enzyme-like chiral plasmonic nanoparticles for optically tunable catalytic cancer therapy. We create chiral plasmonic nanoparticles with glucose oxidase (GOD) and peroxidase (POD) activities, followed by introducing circularly polarized light (CPL). By sequentially activating GOD and POD reactions with right-handed CPL (RC) followed by left-handed CPL (LC), we achieve 1.25- and 1.9-fold enhanced catalytic performance (overall 1.3 times enhancement) compared to non-controlled cascade reactions by creating an optimal acidic environment for the subsequent reaction. Moreover, the D-Au nanoparticle shows a 2-fold higher binding selectivity to D-glucose substrates, attributed to chirality matching. In both cell studies and male mouse models, sequentially irradiated groups (RC followed by LC) exhibit the highest radical generation and the most efficient treatment outcomes compared to the other systems under different irradiation conditions. We believe that our system holds strong potential for medical applications, suggesting a promising platform for catalytic therapy.