Strategies to engineer various nanocarrier-based hybrid catalysts for enhanced chemodynamic cancer therapy.

Chemodynamic therapy (CDT) is a newly developed cancer-therapeutic modality that kills cancer cells by the highly toxic hydroxyl radical (˙OH) generated from the in situ triggered Fenton/Fenton-like reactions in an acidic and H2O2-overproduced tumor microenvironment (TME). By taking the advantage of the TME-activated catalytic reaction, CDT enables a highly specific and minimally-invasive cancer treatment without external energy input, whose efficiency mainly depends on the reactant concentrations of both the catalytic ions and H2O2, and the reaction conditions (including pH, temperature, and amount of glutathione). Unfortunately, it suffers from unsatisfactory therapy efficiency for clinical application because of the limited activators (i.e., mild acid pH and insufficient H2O2 content) and overexpressed reducing substance in TME. Currently, various synergistic strategies have been elaborately developed to increase the CDT efficiency by regulating the TME, enhancing the catalytic efficiency of catalysts, or combining with other therapeutic modalities. To realize these strategies, the construction of diverse nanocarriers to deliver Fenton catalysts and cooperatively therapeutic agents to tumors is the key prerequisite, which is now being studied but has not been thoroughly summarized. In particular, nanocarriers that can not only serve as carriers but are also active themselves for therapy are recently attracting increasing attention because of their less risk of toxicity and metabolic burden compared to nanocarriers without therapeutic capabilities. These therapy-active nanocarriers well meet the requirements of an ideal therapy system with maximum multifunctionality but minimal components. From this new perspective, in this review, we comprehensively summarize the very recent research progress on nanocarrier-based systems for enhanced CDT and the strategies of how to integrate various Fenton agents into the nanocarriers, with particular focus on the studies of therapy-active nanocarriers for the construction of CDT catalysts, aiming to guide the design of nanosystems with less components and more functionalities for enhanced CDT. Finally, the challenges and prospects of such a burgeoning cancer-theranostic modality are outlooked to provide inspirations for the further development and clinical translation of CDT.

Leap-Type Response of Redox/Photo-Active Lanthanide-Based Metal-Organic Frameworks for Early and Accurate Screening of Prostate Cancer.

The development of high-accuracy technologies to distinguish the quite tiny concentration change of tumor markers between negative and positive is of vital significance for early screening and diagnosis of cancers, but is still a great challenge for the conventional biosensors because of their "gradual" detection mode. Herein, a unique "leap-type" responsive lanthanide MOF-based biosensor (designated as Tb-CeMOF-X) with defect-mediated redox-/photo-activities is developed for precisely identifying acid phosphatase (ACP), an early pathological marker of prostate cancer (PCa) in serum. The engineered Tb-CeMOF-X probe achieves a bursting switch-on luminescence at the critical concentration of ACP (9 U ⋅ L-1), while keeping silent below this threshold, undergoing a qualitative signal change from "zero" to "one" between negative and positive indicators and thus significantly improving the identification precision. Significantly, such "leap-type" response performance can be further edited and amplified by rational defect engineering in the crystal structure to improve the accessibility of active centers, consequently maximizing the detection sensitivity toward ACP in the complex biological media. This study proposes the first paradigm for the development of "leap-type" biosensors with ultra-sensitive differentiation capability between negative and positive, and provides a potentially valuable tool for early and accurate screening of PCa.