A dual-catalytic nanoreactor for synergistic chemodynamic-starvation therapy toward tumor metastasis suppression.

Tumor metastasis is extremely deadly for cancer patients and developing effective treatments for deep metastatic tumors remains a major challenge. In this study, we demonstrated a dual-catalytic nanoreactor for tumor metastasis suppression by synergistic Fenton reaction activated chemodynamic therapy (CDT) and glucose oxidase (GOx) initiated starvation therapy. GOx on the surface of hollow mesoporous silica nanoparticles can catalyze the decomposition of intratumoral glucose to generate gluconic acid and H2O2, while Fe3O4 nanoparticles as a Fenton reaction catalyst can in situ catalyze H2O2 to produce highly toxic hydroxyl radicals (˙OH). The oxygen-carrying perfluorohexane (PFC) in the hole of the hollow structures can alleviate the hypoxic environment and promote dual-catalytic reactions. After being disguised by the cancer cell membrane, the delivery efficiency and biological safety of the nanoreactor were effectively improved. The nanoreactor can realize sequential glucose depletion and ˙OH aggregation, which effectively suppress tumor metastasis with negligible side effects.

A cancer cell membrane-camouflaged nanoreactor for enhanced radiotherapy against cancer metastasis.

We report a cancer cell membrane-camouflaged nanoreactor based on a GOx decorated TiO2@MnO2 core-shell structure for enhanced radiotherapy against cancer metastasis. The nanoreactor could specifically target tumor tissues, catalytically oxidize glucose to generate H2O2, and generate abundant ROS under X-ray irradiation.

A cancer cell membrane-encapsulated MnO2 nanoreactor for combined photodynamic-starvation therapy.

We demonstrate a MnO2-based nanoreactor to achieve continuous oxygen generation and efficient conversion from glucose to singlet oxygen for combined photodynamic-starvation therapy.

A pre-protective strategy for precise tumor targeting and efficient photodynamic therapy with a switchable DNA/upconversion nanocomposite.

Tumor-specific targeting based on folic acid (FA) is one of the most common and significant approaches in cancer therapy. However, the expression of folate receptors (FRs) in normal tissues will lead to unexpected targeting and unsatisfactory therapeutic effect. To address this issue, we develop a pre-protective strategy for precise tumor targeting and efficient photodynamic therapy (PDT) using a switchable DNA/upconversion nanocomposite, which can be triggered in the acidic tumor microenvironment. The DNA/upconversion nanocomposite is composed of polyacrylic acid (PAA) coated upconversion nanoparticles (UCNPs), the surface of which is modified using FA and chlorin e6 (Ce6) functionalized DNA sequences with different lengths. Initially, FA on the shorter DNA was protected by a longer DNA to prevent the bonding to FRs on normal cells. Once reaching the acidic tumor microenvironment, C base-rich longer DNA forms a C-quadruplex, resulting in the exposure of the FA groups and the bonding of FA and FRs on cancer cell membranes to achieve precise targeting. Simultaneously, the photosensitizer chlorin e6 (Ce6) gets close to the surface of UCNPs, enabling the excitation of Ce6 to generate singlet oxygen (1O2) under near infrared light via Förster resonance energy transfer (FRET). In vivo experiments indicated that higher tumor targeting efficiency was achieved and the tumor growth was greatly inhibited through the pre-protective strategy.