Conventional detectors are mostly made up of complicated structures that are hard to use. A paper-based microfluidic chip, however, combines the advantages of being small, efficient, easy to process, and environmentally friendly. The paper-based microfluidic chips for biomedical applications focus on efficiency, accuracy, integration, and innovation. Therefore, continuous progress is observed in the transition from single-channel detection to multi-channel detection and in the shift from qualitative detection to quantitative detection. These developments improved the efficiency and accuracy of single-cell substance detection. Paper-based microfluidic chips can provide insight into a variety of fields, including biomedicine and other related fields. This review looks at how paper-based microfluidic chips are prepared, analyzed, and used to help with both biomedical development and functional integration, ideally at the same time.

Free radicals, including reactive oxygen species (ROS), play a critical role in determining cell’s fate. When the level of free radicals is increased to a fatal value, it causes cancer cells to undergo senescence or cell death. Strategies that target this mechanism offer promising therapies against cancer. However, efficient and sustainable systems that generate free radicals, especially oxygen-independent systems, remain deficient. Herein, functionalized PLGA-based nanocomposites that efficiently co-deliver magnetic nanoparticles and 2,2′-azobis­[2-(2-imidazolin-2-yl) propane]-dihydrochloride (AIPH) were fabricated to achieve photothermal-induced thermodynamic therapy combined with macrophage polarization strategies; this therapy targets hypoxic tumors through the generation of an oxygen-independent free-radical cascade. These hybrid NPs can accumulate in the tumor microenvironment, and the encapsulated MNPs not only serve as contrast agents for enhanced magnetic resonance imaging but also exhibit the expected photothermal conversion and trigger the decomposition of AIPH to generate free radicals, thus causing cancer cell death. More importantly, the cell debris from apoptotic or necrotic cancer cells carries nondegraded MNPs, which can be endocytosed by recruited TAMs. MNPs can further induce TAMs to polarize to the M1 subtype to subsequently generate ROS. This study provides an alternative method for the generation of an oxygen-independent free-radical cascade for tumor co-therapy guided by magnetic resonance imaging PTT/TDT.

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Distant metastasis of malignant tumors is considered to be the main culprit for the failure of current antitumor treatments. Conventional single treatments often exhibit limited efficacy in inhibiting tumor metastasis. Therefore, there is a growing interest in developing collaborative antitumor strategies based on photothermal therapy (PTT) and free-radical-generated photodynamic therapy (PDT), especially utilizing oxygen-independent nanoplatforms, to address this challenge. Such antitumor strategies can enhance the therapeutic outcomes by ensuring the cytotoxicity of free radicals even in the hypoxic tumor microenvironment, thereby improving the effective suppression of primary tumors. Additionally, these approaches can stimulate the production of tumor-associated antigens and amplify the immunogenic cell death (ICD) effects, potentially feasible for enhancing the therapeutic outcomes of immunotherapy. Herein, we fabricated a functional nanosystem that co-loads IR780 and 2,2′-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH) to realize PTT-triggered thermodynamic combination therapy via the oxygen-independent pathway for the elimination of primary tumors. Furthermore, the nanocomposites were surface-decorated with a predesigned complex peptide (PLGVRGC-anti-PD-L1 peptide, MMP-sensitive), which facilitated the immunotherapy targeting distant tumors. Through the specific recognition of matrix metalloproteinase (MMP), the sensitive segment on the obtained aNC@IR780A was cleaved. As a result, the freed anti-PD-L1 peptide effectively blocked immune checkpoints, leading to the infiltration and activation of T cells (CTLs). This nanosystem was proven to be effective at inhibiting both primary tumors and distant tumors, providing a promising combination strategy for tumor PTT/TDT/immunotherapy.