Advances in Microfluidic Paper-Based Analytical Devices (µPADs): Design, Fabrication, and Applications.

Microfluidic Paper-based Analytical Devices (µPADs) have emerged as a new class of microfluidic systems, offering numerous advantages over traditional microfluidic chips. These advantages include simplicity, cost-effectiveness, stability, storability, disposability, and portability. As a result, various designs for different types of assays are developed and investigated. In recent years, µPADs are combined with conventional detection methods to enable rapid on-site detection, providing results comparable to expensive and sophisticated large-scale testing methods that require more time and skilled personnel. The application of µPAD techniques is extensive in environmental quality control/analysis, clinical diagnosis, and food safety testing, paving the way for on-site real-time diagnosis as a promising future development. This review focuses on the recent research advancements in the design, fabrication, material selection, and detection methods of µPADs. It provides a comprehensive understanding of their principles of operation, applications, and future development prospects.

Enzyme-Directed and Organelle-Specific Sphere-to-Fiber Nanotransformation Enhances Photodynamic Therapy in Cancer Cells.

Employing responsive nanoplatforms as carriers for photosensitizers represents an effective strategy to overcome the challenges associated with photodynamic therapy (PDT), including poor solubility, low bioavailability, and high systemic toxicity. Drawing inspiration from the morphology transitions in biological systems, a general approach to enhance PDT that utilizes enzyme-responsive nanoplatforms is developed. The transformation of phosphopeptide/photosensitizer co-assembled nanoparticles is first demonstrated into nanofibers when exposed to cytoplasmic enzyme alkaline phosphatase. This transition is primarily driven by alkaline phosphatase-induced changes of the nanoparticles in the hydrophilic and hydrophobic balance, and intermolecular electrostatic interactions within the nanoparticles. The resulting nanofibers exhibit improved ability of generating reactive oxygen species (ROS), intracellular accumulation, and retention in cancer cells. Furthermore, the enzyme-responsive nanoplatform is expanded to selectively target mitochondria by mitochondria-specific enzyme sirtuin 5 (SIRT5). Under the catalysis of SIRT5, the succinylated peptide/photosensitizer co-assembled nanoparticles can be transformed into nanofibers specifically within the mitochondria. The resulting nanofibers exhibit excellent capability of modulating mitochondrial activity, enhanced ROS formation, and significant anticancer efficacy via PDT. Consequently, the enzyme-instructed in situ fibrillar transformation of peptide/photosensitizers co-assembled nanoparticles provides an efficient pathway to address the challenges associated with photosensitizers. It is envisaged that this approach will further expand the toolbox for enzyme-responsive biomaterials for cancer therapy.