ABSTRACT Suction‐based in vivo cutaneous DNA transfection is a newly developed, cost‐effective method that produces high transfection efficiency. This method has shown robust immunogenic responses following SARS‐CoV‐2 DNA vaccination in both pre‐clinical studies and clinical trials. The current work investigates suction‐based transfection and immune activation on a detailed, cellular level. The spatiotemporal patterns of antigen expression in rat skin following suction‐induced delivery of a pEGFP‐N1 plasmid and a SARS‐CoV‐2 DNA vaccine are evaluated via immunofluorescence staining, which demonstrates early and prolonged expression. The epidermis is identified as the primary location of transfection, and the transfected cells are primarily epidermal keratinocytes. Early immune response is assessed by detection of major histocompatibility complex class II‐positive (MHC‐II + ) cells following suction‐induced DNA vaccination.

ABSTRACT Mucoadhesion is an effective approach for increasing the retention time of topical ophthalmic therapeutics, particularly in dry eye, as it may mitigate rapid nasolacrimal drainage and improve their limited bioavailability. Using the gelation properties of mucin, the major glycoprotein of the mucosa, to assemble drug loaded nanocarriers that would consolidate considerably on the ocular mucosa and facilitate sustained release is a facile approach to integrate mucoadhesion into topical formulations. However, mucin‐based nanoparticles tend to aggregate due to their limited stability in colloidal solution form. This study reports on the synthesis and stabilization of mucin in nanoparticle form using alginate as an electrostatic stabilizer, and then the subsequent loading of antioxidant coenzyme Q10. Simultaneous ionotropic gelation of both alginate and mucin is employed to obtain self‐assembling polymeric nanocarriers with superior mucoadhesive properties (>80% adheres to the ocular mucosa for 0.25 gm formulation), improved shelf stability, and desired shear‐thinning behavior whereas coenzyme Q10 was encapsulated with high encapsulation efficiency (>96%) and sustained release for up to 4 days. Extensive in vivo assessment reveals the efficacy of the nanocarriers in improving dry eye symptoms. This study demonstrates a novel and straightforward way to synthesize stabilized alginate‐mucin nanoparticles for the effective delivery of coenzyme Q10.

Abstract Colorectal cancer (CRC) continues to be a major cause of cancer‐related death globally, and in order to overcome obstacles like drug resistance and tumor recurrence, novel therapeutic approaches are required. Using near‐infrared (NIR) photothermal agents to create localized hyperthermia for tumor ablation, photothermal therapy (PTT) presents a promising minimally invasive approach. In this work, a new synergistic strategy is created by loading indirubin (Indi), a bisindole alkaloid with anti‐cancer properties, onto copper sulfide nanoparticles (CuS NPs) that are synthesized using a chemical reduction method. Fourier‐transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), fluorescence microscopy, dynamic light scattering (DLS), and UV–Vis spectroscopy are used to characterize the resultant nanoparticles (Indi‐CuS NPs). Alongside the successful addition of indirubin, UV–Vis spectroscopy verified NIR absorption appropriate for PTT. SEM and FTIR confirm the structural and chemical integrity of Indi‐CuS NPs, while DLS shows a hydrodynamic size of 281.2 nm and a zeta potential of −3.08 mV. These results indicate that Indi‐CuS NPs offer a promising platform for synergistic photothermal therapy (PTT) and chemotherapy against colorectal cancer (CRC) by combining the anti‐cancer potential of indirubin with the high photothermal efficiency of CuS NPs.

Abstract Effective and safe antibiotics active against pathogenic mycobacterial species are needed. Iron is an essential element for bacterial survival. Ga(NO3)3 (GN) and Ga protoporphyrin (GP) as iron mimetics have each been shown to inhibit the iron metabolism and growth of various mycobacterial species. In this study, the dual cyclodextrin nanoparticle (CDGPGN) is prepared that carries GP and GN using a sonication homogenization technique to increase the efficacy of the combination therapy. CDGPGN shows a long‐acting antimicrobial activity against Mycobacteroides abscessus residing in monocyte‐derived macrophages (MDM). A murine pulmonary study showed that the CDGPGN also inhibited the growth of M. abscessus and M. avium complex (MAC) in the lungs. GP induced mycobacterial superoxide dismutase (SOD) activity and reduced catalase activity. GN neither reduces nor increases SOD and catalase activities in mycobacteria. This study confirms that dual CDGPGN nanoparticles containing both GN and GP have potential for development as antimycobacterial agents against M. abscessus.

Abstract The success of medical devices and biomaterials hinges on selecting biological models that truly reflect human physiology and disease. A well‐chosen model is not just a scientific necessity; it is a clinical imperative. Academic biomedical research often relies on readily accessible models that yield affordable, convenient, and predictable results. However, rodent models of sepsis, cancer, and cardiovascular disease frequently fail in clinical translation. Likewise, optimizing a device or material to fit a specific model (“overfitting”) can create false confidence, leading to expensive setbacks. While in vitro systems offer ethical advantages and mechanistic insights, they lack the complexity of living organisms. Animal models, though capable of capturing systemic effects, face species differences, ethical concerns, and poor clinical translation. Advances in 3D tissue engineering, organ‐on‐a‐chip, and humanized models overcome many of these shortcomings, improving predictive accuracy and complementing animal models. Clinician involvement is crucial to aligning preclinical models with real‐world medical needs. Moreover, unnecessary animal experiments should not be conducted or required without a clear translational route. Prioritizing clinically relevant models enhances patient safety, reduces research waste, and drives ethical, impactful medical innovation.

Abstract Photodynamic therapy (PDT) is a clinically approved anticancer treatment based on the generation of reactive oxygen species (ROS) when a photosensitizing agent (PS) is irradiated with specific light. Typically, irradiation is performed to cover the entire tumor or treatment area. However, this approach presents some disadvantages, including irradiation of the surrounding normal tissue. Therefore, this study introduces a novel phototherapeutic approach using single‐point laser irradiation. With the plasma membrane as the primary organelle target, it is demonstrated that single‐point laser irradiation induces plasma membrane damage in cancer cells using two clinically approved fluorescent markers for Glioblastoma: Protoporphyrin IX (PPIX), which localizes to the plasma membrane, and Sodium Fluorescein (NaF), which remains in the extracellular space, contacting the membrane. Single‐point laser irradiation in photodynamic therapy induces plasma membrane disruption in both cases, resulting in selective necrotic cancer cell death. Interestingly, this approach induces cell death from within the spheroids, and the cell death gradually extends to the rest of the spheroid, minimizing damage to the surrounding tissue. In conclusion, this study presents a novel approach using focused laser irradiation and clinically approved dyes to induce precise, targeted cell death within the tumor, suggesting potential for theranostic applications in tumor eradication.

Abstract Smart stimuli‐responsive nanomaterials have emerged as promising candidates in pharmaceutical delivery due to their ability to react to diverse physical, chemical, and biological stimuli. These systems can be precisely engineered to release therapeutic agents in response to specific internal cues, allowing for controlled and targeted interventions tailored to individual patient conditions. Their nanoscale architecture, ease of surface modification, and multifunctional physicochemical properties further enhance their suitability for biomedical applications. Recent advances underscore their potential in treating complex and chronic diseases such as cancer, neurological disorders, and inflammatory conditions, where conventional therapies often fall short. By integrating these responsive nanotechnologies into precision medicine, it is possible to enhance therapeutic efficacy while minimizing systemic toxicity. Herein, this work highlights the ongoing progress in the development and application of stimuli‐responsive nanomedicines. This work also emphasizes the need for extensive clinical validation to determine their long‐term safety and effectiveness in human subjects.