The construction of completely biocompatible and biodegradable tumor suppressors by a simple and reliable method is essential for the clinical application of cancer-targeted drugs. Herein, by inserting glucose oxidase (GOx), catalase (CAT), and chlorin e6 (Ce6) into human serum albumin (HSA) assembly molecules, we constructed a cancer-targeted cascade bioreactor for synergistic starvation and photodynamic therapy (PDT). The modification of HSA could block the GOx activity and reduce the cytotoxicity of normal cells and organs. Through active targeting and passive enhanced permeability and retention effect, the loading of AS1411 could promote the cascade bioreactors to effectively target nucleolin-overexpressed tumors. Once internalized by cancer cells, as a result of catalyzing hydrogen peroxide (H2O2) to produce oxygen (O2), the protein nano-cascade reactor promoted microenvironmental oxygenation, which would subsequently lead to an increase in cytotoxic singlet oxygen (1O2) production under light irradiation as well as the decomposition of intracellular glucose. In vitro and in vivo studies showed that the cascaded nanoreactors could significantly enhance therapeutic efficacy through synergistic starvation therapy and enhanced PDT as well as chemotherapy. This cascade strategy will be demonstrated in clinical applications with huge potential.

In this work, the development of riboflavine sodium phosphate (RFSP) decorated WS 2 nanosheets and their usability for electrochemical monitoring of hybridization of nucleic acids have been achieved. The RFSP molecules performed as highly efficient stabilizer for ultrasonically dispersing WS 2 nanosheets in an aqueous solution, as well as providing the inherent self-redox signal for sensing DNA immobilization and hybridization. The probe ssDNA was noncovalently assembled on the fabricated RFSP/WS 2 nanocomposite surface through the π-π interaction between the conjugated nanocomposite and nucleic acids bases. The formed dsDNA after the hybridization of the probe with the target could be released off the surface of the conjugated nanocomposite because of the burying of DNA bases. This constructed genosensor permits quantitative determination of PIK3CA gene in the range of 1.0 × 10 −16 to 1.0 × 10 −8 mol l −1 with a detection limit as low as 2.1 × 10 −17 mol l −1 . The proposed platform exhibited a desirable differentiation capability against complementary, noncomplementary and base-mismatched sequences along with favorable stability and reproducibility. This approach of genosensing can provide a facile and rapid mode for DNA determination without the utilization of additional labels.

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