Biodegradable polymers such as Polycaprolactone (PCL), Polylactic acid (PLA), and Poly(lactic-co-glycolic acid) (PLGA) are attracting attention as key platforms for anticancer drug delivery systems due to their excellent biocompatibility and controllable degradation rates. These polymers can overcome limitations of existing chemotherapeutics, such as low bioavailability, systemic toxicity, and nonspecific cell damage, and contribute to the development of precision medicine approaches and long-acting therapeutics. This paper discusses the chemical and physicochemical properties of these three polymers, their synthetic strategies, and the controlled drug release technology through surface functionalization and stimuli-responsive design. Furthermore, we highlight their potential for use in various formulations, including micelles, nanoparticles, hydrogels, and microspheres, enabling enhanced drug solubility, sustained release, and tumor targeting. Preclinical and clinical applications demonstrate that these polymer-based DDSs represent a promising approach for implementing next-generation precision anticancer treatment strategies, with further potential for clinical translation and widespread adoption.

Recently, extracellular vesicles (EVs) have emerged as pivotal mediators of intercellular communication that reflect physiological homeostasis and pathological alterations. By encapsulating diverse biomolecules, including proteins, nucleic acids, and lipids, EVs mirror the molecular signatures of their parent cells, thereby positioning EV-based biosensing as a transformative platform for noninvasive diagnostics, prognostic prediction, and therapeutic monitoring. This review provides a comprehensive overview of the current state and clinical translation of EV biosensing technologies. Herein, we have discussed ongoing efforts toward standardization and analytical validation (e.g., MISEV2023 and EV-TRACK) and evaluated advances in sensing modalities such as surface plasmon resonance (SPR), electrochemical, fluorescence, and magnetic detection systems, which have significantly improved analytical performance in terms of sensitivity and specificity. Furthermore, we highlight recent developments in multiplexed and multiomics integration at the single-EV level and the application of machine learning to enhance diagnostic accuracy and interpret biological heterogeneity. The clinical relevance of EV biosensing has been explored across multiple disease domains, including oncology, neurology, and cardiometabolic and infectious diseases, with an emphasis on translational progress toward standardized, regulatory-compliant, and scalable platforms. Finally, this review identifies key challenges in manufacturing scale-up, quality control, and point-of-care deployment and proposes a unified framework to accelerate the adoption of EV biosensing as a cornerstone of next-generation precision diagnostics and personalized medicine.

Heat shock protein 90 (HSP90) is a molecular chaperone that plays a pivotal role in the stabilization and functional activation of numerous oncoproteins and signaling molecules essential for cancer cell survival and proliferation. Despite the extensive development and clinical evaluation of HSP90 inhibitors, their therapeutic potential as monotherapies has been limited by suboptimal efficacy, dose-limiting toxicity, and the emergence of drug resistance. Recent studies have demonstrated that combination therapies involving HSP90 inhibitors and other anticancer agents such as chemotherapeutics, targeted therapies, and immune checkpoint inhibitors can enhance anticancer activity, overcome resistance mechanisms, and modulate the tumor microenvironment. These synergistic effects are mediated by the concurrent degradation of client proteins, the disruption of signaling pathways, and the enhancement of antitumor immunity. However, the successful clinical implementation of such combination strategies requires the careful optimization of dosage, administration schedules, toxicity management, and patient selection based on predictive biomarkers. In this review, we provide a comprehensive overview of the mechanistic rationale, preclinical and clinical evidence, and therapeutic challenges associated with HSP90 inhibitor-based combination therapies. We also discuss future directions leveraging emerging technologies including multi-omics profiling, artificial intelligence, and nanoparticle-mediated delivery for the development of personalized and effective combination regimens in oncology.

Empathy, crucial for social interaction, is impaired across various neuropsychiatric conditions. However, the genetic and neural underpinnings of empathy variability remain elusive. By combining forward genetic mapping with transcriptome analysis, we discover that aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) is a key driver modulating observational fear, a basic form of affective empathy. Disrupted ARNT2 expression in the anterior cingulate cortex (ACC) reduces affect sharing in mice. Specifically, selective ARNT2 ablation in somatostatin (SST)-expressing interneurons leads to decreased pyramidal cell excitability, increased spontaneous firing, aberrant Ca²⁺ dynamics, and disrupted theta oscillations in the ACC, resulting in reduced vicarious freezing. We further demonstrate that ARNT2-expressing SST interneurons govern affective state discrimination, uncovering a potential mechanism by which ARNT2 polymorphisms associate with emotion recognition in humans. Our findings advance our understanding of the molecular mechanism controlling empathic capacity and highlight the neural substrates underlying social affective dysfunctions in psychiatric disorders.

Next-generation cancer immunotherapy increasingly combines tumor-targeting antibodies or antibody–drug conjugates (ADCs) with immune effector cells to enhance therapeutic precision. However, many existing approaches rely on genetic modification or complex manufacturing, limiting their clinical scalability and rapid deployment. To address this issue, we developed an antibody capture protein (ACP)-based surface engineering platform that enables the rapid, reversible, and non-genetic functionalization of NK cells with therapeutic antibodies or ADCs. This approach uses a DMPE-PEG-lipid conjugate to anchor thiolated protein A (ACP) to the NK cell membrane via hydrophobic insertion, thereby stably and selectively binding to the Fc region of IgG molecules. Using this strategy, we developed ACP-modified NK cells (AC-NKs) that can selectively capture therapeutic antibodies (trastuzumab (TZ), trastuzumab-emtansine (T-DM1), and sacituzumab (SZ)) pre-bound to each target antigen on tumor cells and induce antigen-specific cytotoxic responses. The resulting AC-NKs exhibited enhanced tumor recognition and cytotoxicity against HER2-positive and Trop-2-positive cancer cells in vitro. Compared with conventional combination therapies, AC-NKs enhanced immune activation, as demonstrated by effective delivery of cytotoxic agents, enhanced cancer cell engagement, and upregulation of CD107a expression. Notably, the system supports multiple antigen targeting and tunable antibody loading, enabling adaptation to tumor heterogeneity and resistant phenotypes. This platform might also provide a simple, scalable, and safe method for rapidly developing programmable immune cell therapies without genetic modification. Its versatility supports multi-antigen targeting and broad applicability across NK and T cell therapies, offering a promising path toward personalized, off-the-shelf chemoimmunotherapy.

The brain is a spatially organized tissue where the molecular characteristics of each cell are closely linked to its anatomical location. However, conventional bulk and single-cell RNA sequencing lose this spatial context during the tissue separation process. Spatial transcriptomics (ST) overcomes these limitations by measuring gene expression while preserving the positional information of cells within intact tissues, making it a powerful approach for elucidating the cellular and molecular heterogeneity that defines brain structure and disease. This review summarizes the two main types of ST technology: next-generation sequencing (NGS)-based platforms (Visium, Stereo-Seq, Slide-Seq) and in situ platforms (MERFISH, seqFISH+, Xenium). NGS-based platforms provide unbiased whole-transcriptome profiling across extensive tissue regions, while in situ platforms offer subcellular resolution within individual cells. We aim to assist in platform selection by comparing the principles, advantages, and limitations of each platform. Next, we focus on how spatial sequencing (ST) has been utilized to analyze the spatial heterogeneity of aging and diseased brains, and examine region- and cell-type changes observed in brain aging, the lesion-related microenvironments of Alzheimer’s and Parkinson’s diseases, and the spatially isolated tumor cell states and immunosuppressive environments of glioblastoma. We also introduce the key brain ST data resources that underpin these studies. Collectively, ST is emerging as an essential tool for understanding the spatial logic of brain function and pathology, demonstrating increasingly greater potential in the field of precision medicine.