Artificial Metalloprotein Nanoanalogues: In Situ Catalytic Production of Oxygen to Enhance Photoimmunotherapeutic Inhibition of Primary and Abscopal Tumor Growth.

Photoimmunotherapy (PIT) has shown enormous potential in not only eliminating primary tumors, but also inhibiting abscopal tumor growth. However, the efficacy of PIT is greatly limited by tumor hypoxia, which causes the attenuation of phototherapeutic efficacy and is a feature of the immunosuppressive tumor microenvironment (TME). In this study, one type of brand-new artificial metalloprotein nanoanalogues is developed via reasonable integration of a "phototherapy-enzymatic" RuO2 and a model antigen, ovalbumin (OVA) for enhanced PIT of cancers, namely, RuO2 -hybridized OVA nanoanalogues (RuO2 @OVA NAs). The RuO2 @OVA NAs exhibit remarkable photothermal/photodynamic capabilities under the near-infrared light irradiation. More importantly, the photoacoustic imaging and immunofluorescence staining confirm that RuO2 @OVA NAs can remarkably alleviate hypoxia via in situ catalysis of hydrogen peroxide overexpressed in the TME to produce oxygen (O2 ). This ushers a prospect of concurrently enhancing photodynamic therapy and reversing the immunosuppressive TME. Also, OVA, as a supplement to the immune stimulation induced by phototherapy, can activate immune responses. Finally, further combination with the cytotoxic T-lymphocyte-associated protein 4 checkpoint blockade is reported to effectively eliminate the primary tumor and inhibit distant tumor growth via the abscopal effect of antitumor immune responses, prolonging the survival.

Water-soluble hyaluronic acid-hybridized polyaniline nanoparticles for effectively targeted photothermal therapy.

The construction of advanced phototherapy systems with high therapeutic efficacy toward cancer and low side effects, especially targeted species, is highly desirable. Herein, we developed one kind of water-soluble hyaluronic acid-hybridized polyaniline nanoparticles (HA-PANI NPs) as a nanoplatform for photothermal therapy (PTT) with targeted specificity of a CD44-mediated cancer cell. The water-soluble HA-PANI NPs were fabricated by one-step oxidative polymerization using aniline as a polymerizable monomer and HA as a stabilizer and targeted agent, where non-covalent electrostatic interaction between the negatively charged polymer HA and the cationic polymer PANI drives the formation of HA-PANI NPs. It was demonstrated that approximately spherical HA-PANI NPs are well-dispersed in aqueous solutions, with average hydrodynamic diameters of around 100 nm. Besides, HA-PANI NPs have negligible cytotoxicity in vitro, which facilitates biomedical applications with low toxicity. We studied the in vitro photothermal cell-killing efficacy of HA-PANI NPs by MTT assay and confocal microscopy measurement. The results reveal that HA-PANI NPs can selectively kill the cancer cells of HeLa and HCT-116 cells rather than normal cells of HFF cells upon exposure to a NIR 808 nm laser. The efficient intracellular intake of the HA-PANI NPs by both HeLa and HCT-116 cells are observed, confirming their targeting ability for CD44-overexpressing cancer cells. Furthermore, the results of in vivo photothermal ablation of tumors show excellent treatment efficacy, indicating that the HA-PANI NPs can be considered as an extremely promising nanoplatform for targeted PTT of cancer.

One-step preparation of a water-soluble carbon nanohorn/phthalocyanine hybrid for dual-modality photothermal and photodynamic therapy.

The biomedical applications of carbon nanomaterials, especially integrating noninvasive photothermal therapy (PTT) and photodynamic therapy (PDT), into a single system have enormous potential in cancer therapy. Herein, we present a novel and facile one-step method for the preparation of water-soluble single-walled carbon nanohorns (SWNHs) and metal phthalocyanines (MPc) hybrid for PTT and PDT. The hydrophilic MPc, tetrasulfonic acid tetrasodium salt copper phthalocyanine (TSCuPc), is coated on the surface of SWNHs via noncovalent π-π interaction using the sonication method. In this PTT/PDT nanosystem, SWNHs acts as a photosensitizer carrier and PTT agent, while TSCuPc acts as a hydrophilic and PDT agent. The EPR results demonstrated that the generated reactive oxygen species (ROS) not only from the photoinduced electron transfer process from TSCuPc to SWNHs but also from SWNHs without exciting TSCuPc to its excited state. The test of photothermal conversion proved that not only do SWNHs contribute to the photothermal therapy (PTT) effect, TSCuPc probably also contributes to that when it coats on the surface of SWNHs upon exposure to a 650-nm laser. More importantly, the results of in vitro cell viability revealed a significantly enhanced anticancer efficacy of combined noninvasive PTT/PDT, indicating that the SWNHs-TSCuPc nanohybrid is a hopeful candidate material for developing an efficient and biocompatible nanoplatform for biomedical application.

Graphene loading water-soluble phthalocyanine for dual-modality photothermal/photodynamic therapy via a one-step method.

In this paper, we present a new and facile one-step method for the fabrication of a water-soluble graphene-phthalocyanine (GR-Pc) hybrid material by simply sonicating GR with a hydrophilic Pc, tetrasulfonic acid tetrasodium salt copper phthalocyanine (TSCuPc). In the resultant hybrid material, TSCuPc is coated on the skeleton of pristine GR via non-covalently π-π interaction, detailedly characterized by UV-vis/Raman spectra, X-ray photoelectron spectroscopy (XPS), etc. The obtained GR-Pc hybrid (GR-TSCuPc) is applied for photothermal therapy (PTT) and photodynamic therapy (PDT). In this PTT/PDT system, both GR and TSCuPc operate as multifunctional agents: GR acts as a photosensitizer carrier and PTT agent, while TSCuPc acts as a hydrophilic PDT agent. Furthermore, the results of cell viability show that the phototherapy effect of GR-TSCuPc is observably higher than that of free TSCuPc, indicating that combined noninvasive PTT/PDT exhibits better anti-cancer efficacy in vitro. Such results highlight that this work provide a facile method to develop efficacious dual-modality carbon nanoplatform for developing cancer therapeutics.