Although photodynamic therapy (PDT) has been clinically applied tumor hypoxia still greatly restricts the performance of this oxygen-dependent oncological treatment. The delivery of oxygen donors to tumor may produce excessive reactive oxygen species (ROS) and damage the peripheral tissues. Herein, we developed a strategy to solve the hypoxia issue by enhancing the lethality of ROS. Before PDT, the ROS-defensing system of the cancer cells was obstructed by an inhibitor to MTH1, which is a key for the remediation of ROS-caused DNA damage. As a result, both nuclei and mitochondrial DNA damages were increased, remarkably promoting cellular apoptosis. The therapeutic results demonstrated that the performance of PDT can be improved by the MTH1 inhibitor, leading to efficient cancer cell killing effect in the hypoxic tumor. This strategy makes better use of the limited oxygen, holding the promise to achieve satisfactory therapeutic effect by PDT without generating redundant cytotoxic ROS.
The sensing and visualized monitoring of hydrogen sulfide (H 2 S) in vivo is crucial to understand its physiological and pathological roles in human health and diseases. Common methods for H 2 S detection require the destruction of the biosamples and are not suitable to be applied in vivo. In this Communication, we report a "turn-on" second near-infrared (NIR-II) luminescent approach for sensitive, real-time, and in situ H 2 S detection, which is based on the absorption competition between the H 2 S-responsive chromophores (compound 1) and the NIR-II luminescent lanthanide nanoparticles. Specifically, the luminescence was suppressed by compound 1 due to the competitive absorption of the incident light. In the presence of H 2 S, the compound 1 was bleached to recover the luminescence. Thanks to the deep tissue penetration depth and the low absorbance/scattering on biological samples of the NIR-II nanoprobes, the monitoring of the endogenous H 2 S in lipopolysaccharide-induced liver inflammation was achieved, which is unattainable by the conventional histopathological and serological approaches.
Nanoparticle-based delivery systems (NDS) have impacted the field of cancer therapy on account of the enhanced permeability and retention (EPR) effect that promotes passive accumulation in tumors through the tumor vasculature after intravenous (IV) administration. However, transplanted tumor xenografts on animal models used to justify the feasibility of EPR effect are quite different from clinical tumors in many aspects, a fact which becomes an impediment for NDS to succeed clinical trials. Particularly, early stage tumor metastases are usually non-vascularized and incapable of conforming the EPR effect after IV injection.Therefore, it is necessary to develop smart NDS to deliver drugs in an EPR-independent route.Herein, we report an NDS-based treatment approach for intra-abdominal metastases from ovarian carcinoma. Instead of IV injection, intraperitoneal (IP) injection was employed to directly apply the NDS to the metastatic lesions. The NDS was tailor-made with targeting groups to actively target the tumor nidus and redox-responsive drug release to reduce systematic toxicity. Comparing with IV administration, the IP injected NDS could be enriched in metastatic tumor more efficiently, leading to superior therapeutic outcome in vivo. This study provides a successful protocol of EPR-independent NDS-based cancer treatment, which may facilitate the clinical translation of nanoparticle-based cancer therapeutics.
The ability to incorporate functional metal ions (Mn+) into metal–organic coordination complexes adds remarkable flexibility in the synthesis of multifunctional organic–inorganic hybrid materials with tailorable electronic, optical, and magnetic properties. We report the cation‐exchanged synthesis of a diverse range of hollow Mn+‐phytate (PA) micropolyhedra via the use of hollow Co2+‐PA polyhedral networks as templates at room temperature. The attributes of the incoming Mn+, namely Lewis acidity and ionic radius, control the exchange of the parent Co2+ ions and the degree of morphological deformation of the resulting hollow micropolyhedra. New functions can be obtained for both completely and partially exchanged products, as supported by the observation of Ln3+ (Ln3+=Tb3+, Eu3+, and Sm3+) luminescence from as‐prepared hollow Ln3+‐PA micropolyhedra after surface modification with dipicolinic acid as an antenna. Moreover, Fe3+‐ and Mn2+‐PA polyhedral complexes were employed as magnetic contrast agents.
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