Biodegradable Mesoporous Organosilica Nanosheets for Chemotherapy/Mild Thermotherapy of Cancer: Fast Internalization, High Cellular Uptake, and High Drug Loading.

The choice of nanocarriers is crucial to fabricate ideal therapeutic nanoplatform in the treatment of cancer. Considering the advantages brought by the two-dimensional (2D) materials with atomic thickness in drug loading and cellular uptake, herein, novel 2D biodegradable mesoporous organosilica nanosheets (MONSs) are presented, and their application in chemotherapy/mild thermotherapy of cancer is studied by loading chemotherapy drug doxorubicin (DOX) and conjugating ultrasmall CuS nanoparticles. It is found that the loading of DOX in MONSs is as high as 859 µg/mg due to their large surface area and intermediate void structure. The release of DOX from MONSs is intelligently controlled by pH value, glutathione (GSH) concentration, and laser irradiation. Excitingly, in comparison with traditional spherical mesoporous organosilica nanoparticles, as-prepared MONSs not only show more rapid degradation but also exhibit faster internalization and higher cellular uptake efficiency due to their larger aspect ratios and unique cellular internalization approach of 2D materials. A mild thermotherapy induced by ultrasmall CuS nanoparticles can further promote the cellular uptake and improve chemotherapy efficacy. The in vitro and in vivo experimental results reveal that the theranostic nanoplatform based on degradable MONSs has excellent biocompatibility and anticancer effects. Therefore, MONSs are expected to be a competitive alternative to existing silica-based nanomaterials in antitumor treatment.

A metal-phenolic network-based multifunctional nanocomposite with pH-responsive ROS generation and drug release for synergistic chemodynamic/photothermal/chemo-therapy.

Developing multifunctional nanomaterials with chemodynamic therapy (CDT)-based combination therapy has increasingly become a promising strategy for cancer treatment. Herein, a metal-phenolic network-based multifunctional nanocomposite (PID@Fe-TA) via the noncovalent interaction of multiple nontoxic raw materials has been designed to integrate the synergistic effect of CDT, photothermal therapy (PTT) and chemotherapy into one nanoplatform for breast cancer treatment. Benefiting from the pH-responsive properties and the assistance of near infrared (NIR) laser irradiation, the outer shell Fe3+-tannic acid (TA) complexes of PID@Fe-TA can be easily degraded into Fe3+ and TA as well as to release chemotherapeutic drugs (doxorubicin, DOX) and photothermal transforming agents (indocyanine green, ICG) in a tumor microenvironment (TME) or cancer cells. The released TA can accelerate the reduction of Fe3+ to Fe2+ for ensuring effective conversion of hydrogen peroxide (H2O2) into a highly toxic hydroxyl radical (˙OH) via the Fenton reaction. The exposed DOX can enter the cell nucleus to induce chemotherapy. The released ICG can locate the distribution of nanocomposites in the body. Besides, the heat generated from PID@Fe-TA after NIR laser irradiation can further promote the therapeutic effect of PPT-enhanced CDT. Importantly, an excellent therapeutic efficacy is achieved both in in vitro and in vivo via the CDT/PTT/chemotherapy combination based on this "all-in-one" nanoplatform, providing a good paradigm for effective cancer eradication.

Encapsulation of glucose oxidase in Fe(III)/tannic acid nanocomposites for effective tumor ablation via Fenton reaction.

Increasing the content of reactive oxygen species (ROS) with the assistance of nanoformulations in cancer cells via the Fenton reaction is considered an effective method to treat cancer. However, the efficiency of the Fenton reaction is affected by the level of H2O2, the selection of iron ions in different nanoformulations, etc. Herein, we use FeIII-tannic acid (FeIIITA) nanocomposites as the carrier to deliver glucose oxidase (GOD) which can solve the problem of insufficient endogenous H2O2 by catalytically converting the glucose. In comparison with traditional Fe2+/Fe3+, FeIIITA nanocomposites perform higher catalytic activity in converting H2O2 to high toxic hydroxyl radicals (·OH) due to the TA-mediated reduction of Fe3+. So, the integration of GOD and TA in the construction of nanocomposites significantly enhances the efficiency of the Fenton reaction. In vitro experiments show that ·OH produced by GOD-FeIIITA nanocomposites can not only achieve a good anticancer effect at a low concentration but also promote degradability of the nanocomposites. When it is only 1.08 µg · ml-1, the cell apoptosis rate has reached 76.91%. In vivo experiments further demonstrate that GOD-FeIIITA nanocomposites can significantly inhibit tumor growth. So this work lays a good foundation for Fenton reaction-based cancer treatment.

Sulfosalicylic acid/Fe3+ based nanoscale coordination polymers for effective cancer therapy by the Fenton reaction: an inspiration for understanding the role of aspirin in the prevention of cancer.

Fenton reaction-based reactive oxygen species (ROS) generation provides a new idea for the design of ROS-mediated anticancer agents. Finding ways to increase iron uptake and to elevate the level of H2O2 in cells simultaneously is thus crucial to this strategy. Meanwhile, salicylic acid (SA) or its analogue, as the major metabolite of aspirin, has been reported to be closely associated with an intracellular redox-active product. In this work, a PEG-modified nanoscale coordination polymer (PFNC) via the self-assembly of 5-sulfosalicylic acid (SSA) with Fe3+ ions has been designed for the first time. The results show that the SSA dissociated from the PFNC can lead to the decrease of GSH and the accumulation of H2O2 in cancer cells, and thus elevate cellular ROS via the Fenton reaction. Owing to such intracellular oxidative stress, PFNC-induced ferroptotic cell death was further confirmed. In vitro cytotoxicity studies show that PFNCs display higher cytotoxicity on cancer cells than on normal cells. In vivo experiments further demonstrate that PFNCs not only possess high tumor accumulation, but also significantly inhibit the tumor growth without obvious damage toward the major organs. Based on the results, we expect that this work will provide an inspiration for understanding the role of SA, even aspirin, in the prevention of cancer.