Transformable Spinose Nanodrums with Self-Supplied H2 O2 for Photothermal and Cascade Catalytic Therapy of Tumor.

Advances in enzymes involve an efficient biocatalytic process, which has demonstrated great potential in biomedical applications. However, designing a functional carrier for enzymes equipped with satisfactory degradability and loading efficiency, remains a challenge. Here, based on transformable liquid metal (LM), a spinose nanodrum is designed as protein carrier to deliver enzyme for tumor treatment. With the assistance of spines and a special drum-like shape, it is found that the spiny LM can carry much more enzymes than spherical LM under the same condition. Benefiting from the satisfactory enzyme loading efficiency of spiny LM, a plasma amine oxidase immobilized spinose LM nanosystem enveloped with epigallocatechin gallate (EGCG)-Fe3+ (LMPE) is fabricated for photothermal and cascade catalytic tumor therapy. Activated by the acidic condition in the tumor microenvironment, the LMPE can oxidize spermine (Spm) and spermidine (Spd) to generate hydrogen peroxide (H2 O2 ) for Fenton catalytic reaction to produce the lethal hydroxyl radical (•OH) for tumor cell killing. Combined with remarkable photothermal performance of LM, LMPE exhibits significant inhibition of tumor in vivo.

Integration of a porous coordination network and black phosphorus nanosheets for improved photodynamic therapy of tumor.

Selectively attenuating the protection offered by heat shock protein 90 (HSP90), which is indispensable for the stabilization of the essential regulators of cell survival and works as a cell guardian under oxidative stress conditions, is a potential approach to improve the efficiency of cancer therapy. Here, we designed a biodegradable nanoplatform (APCN/BP-FA) based on a Zr(iv)-based porphyrinic porous coordination network (PCN) and black phosphorus (BP) sheets for efficient photodynamic therapy (PDT) by enhancing the accumulation of the nanoplatforms in the tumor area and attenuating the protection of cancer cells. Owing to the favorable degradability of BP, the nanosystem exhibited accelerated the release of the HSP90 inhibitor tanespimycin (17-AAG) and an apparent promotion in the reactive oxygen species (ROS) yield of PCN as well as expedited the degradation of the PCN-laden BP nanoplatforms. Both in vitro and in vivo results revealed that the elevated amounts of ROS and reduced cytoprotection in tumor cells were caused by the nanoplatforms. This strategy may provide a promising method for attenuating cytoprotection to aid efficient photodynamic therapy.

A MSN-based tumor-targeted nanoplatform to interfere with lactate metabolism to induce tumor cell acidosis for tumor suppression and anti-metastasis.

Lactate, the main contributor to the acidic tumor microenvironment, not only promotes the proliferation of tumor cells, but also closely relates to tumor invasion and metastasis. Here, a tumor targeting nanoplatform, designated as Me&Flu@MSN@MnO2-FA, was fabricated for effective tumor suppression and anti-metastasis by interfering with lactate metabolism of tumor cells. Metformin (Me) and fluvastatin sodium (Flu) were incorporated into MnO2-coated mesoporous silicon nanoparticles (MSNs), the synergism between Me and Flu can modulate the pyruvate metabolic pathway to produce more lactate, and concurrently inhibit lactate efflux to induce intracellular acidosis to kill tumor cells. As a result of the restricted lactate efflux, the extracellular lactate concentration is reduced, and the ability of the tumor cells to migrate is also weakened. This ingenious strategy based on Me&Flu@MSN@MnO2-FA showed an obvious inhibitory effect on tumor growth and resistance to metastasis.