Emerging nanocatalytic tumor therapies based on nontoxic but catalytically active inorganic nanoparticles (NPs) for intratumoral production of high‐toxic reactive oxygen species have inspired great research interest in the scientific community. Nanozymes exhibiting natural enzyme‐mimicking catalytic activities have been extensively explored in biomedicine, mostly in biomolecular detection, yet much fewer researches are available on specific nanocatalytic tumor therapy. This study reports on the construction of an efficient biomimetic dual inorganic nanozyme‐based nanoplatform, which triggers cascade catalytic reactions for tumor microenvironment responsive nanocatalytic tumor therapy based on ultrasmall Au and Fe 3 O 4 NPs coloaded dendritic mesoporous silica NPs. Au NPs as the unique glucose oxidase‐mimic nanozyme specifically catalyze β‐D‐glucose oxidation into gluconic acid and H 2 O 2 , while the as produced H 2 O 2 is subsequently catalyzed by the peroxidase‐mimic Fe 3 O 4 NPs to liberate high‐toxic hydroxyl radicals for inducing tumor‐cell death by the typical Fenton‐based catalytic reaction. Extensive in vitro and in vivo evaluations have demonstrated high nanocatalytic‐therapeutic efficacy with a desirable tumor‐suppression rate (69.08%) based on these biocompatible composite nanocatalysts. Therefore, this work paves a way for nanocatalytic tumor therapy by rationally designing inorganic nanozymes with multienzymatic activities for achieving high therapeutic efficacy and excellent biosafety simultaneously.
Cell-based drug delivery systems have shown promising capability for tumor-targeted therapy owing to the intrinsic tumor-homing and drug-carrying property of some living cells. However, imaging tracking of their migration and bio-effects is urgently needed for clinical application, especially for glioma. Here, we report the inflammation-activatable engineered neutrophils by internalizing doxorubicin-loaded magnetic mesoporous silica nanoparticles (ND-MMSNs) which can provide the potential for magnetic resonance (MR) imaging tracking of the drug-loaded cells to actively target inflamed brain tumor after surgical resection of primary tumor. The phagocytized D-MMSNs possess high drug loading efficiency and do not affect the host neutrophils’ viability, thus remarkably improving intratumoral drug concentration and delaying relapse of surgically treated glioma. Our study offers a new strategy in targeted cancer theranostics through combining the merits of living cells and nanoparticle carriers.
The blood brain barrier is the main obstacle to delivering diagnostic and therapeutic agents to the diseased sites of brain. It is still of great challenge for the combined use of focused ultrasound (FUS) and theranostic nanotechnology to achieve noninvasive and localized delivery of chemotherapeutic drugs into orthotopic brain tumor. In this work, a unique theranostic nanoplatform for highly efficient photoacoustic imaging‐guided chemotherapy of brain tumor both in vitro and in vivo, which is based on the utilization of hollow mesoporous organosilica nanoparticles (HMONs) to integrate ultrasmall Cu2− xSe particles on the surface and doxorubicin inside the hollow interior, is synthesized. The developed multifunctional theranostic nanosystems exhibit tumor‐triggered programmed destruction due to the reducing microenvironment‐responsive cleavage of disulfide bonds that are incorporated into the framework of HMONs and linked between HMONs and Cu2− xSe, resulting in tumor‐specific biodegradation and on‐demand drug‐releasing behavior. Such tumor microenvironment‐responsive biodegradable and biocompatible theranostic nanosystems in combination with FUS provide a promising delivery nanoplatform with high performance for orthotopic brain tumor imaging and therapy.
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