Fabrication of an Au-doped Cu/Fe oxide-polymer core-shell nanoreactor with chemodynamic and photodynamic dual effects as potential cancer therapeutic agents.

Nanoparticles are widely used in biomedical applications and cancer treatments due to their minute scale, multi-function, and long retention time. Among the various nanoparticles, the unique optical property derived from the localized surface plasmon resonance effect of metallic nanoparticles is a primary reason that metallic nanoparticles are researched and applied. Copper and Iron nanoparticles have the potential to generate hydroxyl radicals in excess H2O2 via Fenton or Fenton-like reactions. On the other hand, gold nanoparticles equipped with a photosensitizer can transfer the energy of photons to chemical energy and enhance the production of singlet oxygen, which is suitable for cancer treatment. With the actions of these two reactive oxygen species in the tumor microenvironment, cell apoptosis can further be induced. In this work, we first synthesized dual metal nanoparticles with poly[styrene-alt-(maleic acid, sodium salt)(Cu ferrite oxide-polymer) by a simple one-step hydrothermal reduction reaction. Then, gold(III) was reduced and doped into the structure, which formed a triple metal structure, Au-doped Cu ferrite nanoparticles (Au/Cu ferrite oxide-polymer NPs). The metal ratio of the product could be controlled by manipulating the Fe/Cu ratio of reactants and the sequence of addition of reactants. The core-shell structure was verified by transmission electron microscopy. Moreover, the hydroxyl radical and singlet oxygen generation ability of Au/Cu ferrite oxide-polymer was proved. The chemodynamic and photodynamic effect was measured, and the in vitro ROS generation was observed. Furthermore, the behavior of endocytosis by cancer cells could be controlled by the magnetic field. The result indicated that Au/Cu ferrite oxide-polymer core-shell nanoreactor is a potential agent for chemodynamic/photodynamic synergetic therapy.

Iron oxide@chlorophyll clustered nanoparticles eliminate bladder cancer by photodynamic immunotherapy-initiated ferroptosis and immunostimulation.

The escape of bladder cancer from immunosurveillance causes monotherapy to exhibit poor efficacy; therefore, designing a multifunctional nanoparticle that boosts programmed cell death and immunoactivation has potential as a treatment strategy. Herein, we developed a facile one-pot coprecipitation reaction to fabricate cluster-structured nanoparticles (CNPs) assembled from Fe3O4 and iron chlorophyll (Chl/Fe) photosensitizers. This nanoassembled CNP, as a multifunctional theranostic agent, could perform red-NIR fluorescence and change the redox balance by the photoinduction of reactive oxygen species (ROS) and attenuate iron-mediated lipid peroxidation by the induction of a Fenton-like reaction. The intravesical instillation of Fe3O4@Chl/Fe CNPs modified with 4-carboxyphenylboronic acid (CPBA) may target the BC wall through glycoproteins in the BC cavity, allowing local killing of cancer cells by photodynamic therapy (PDT)-induced singlet oxygen and causing chemodynamic therapy (CDT)-mediated ferroptosis. An interesting possibility is reprogramming of the tumor microenvironment from immunosuppressive to immunostimulatory after PDT-CDT treatment, which was demonstrated by the reduction of PD-L1 (lower "off" signal to the effector immune cells), IDO-1, TGF-ß, and M2-like macrophages and the induction of CD8+ T cells on BC sections. Moreover, the intravesical instillation of Fe3O4@Chl/Fe CNPs may enhance the large-area distribution on the BC wall, improving antitumor efficacy and increasing survival rates from 0 to 91.7%. Our theranostic CNPs not only demonstrated combined PDT-CDT-induced cytotoxicity, ROS production, and ferroptosis to facilitate treatment efficacy but also opened up new horizons for eliminating the immunosuppressive effect by simultaneous PDT-CDT.