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Mesothelin targeted nano-system enhanced chemodynamic therapy and tirapazamine chemotherapy via lactate depletion
Nano Research 2023, 16 (5): 7108-7118
Published: 14 January 2023
Downloads:60

The enhanced permeability and retention (EPR) effect alone is not enough for nanoparticles to reach the target. Combination of active and passive targeting may be an effective drug delivery route. Hollow ferric-tannic acid complex nanocapsules (HFe-TA) may effectively degrade and release Fe2+ ions, and Fe2+ ions induce the production of ·OH, however, the fenton reaction needs amount of H2O2 to enhance chemodynamic therapy. Due to their deficiencies, such nanoparticles cannot realize intravenous drug delivery. Here, the mesothelin-targeted membrane (MTM) was constructed to realize accurate delivery nano-system, and mesothelin antibody was expressed on the 293T cell membrane to prepare a MTM. Lactate oxidase (Lox) was loaded on HFe-TA to obtain Lox@HFe-TA. Lox@HFe-TA was coated with MTM to develop the MTM nanosystem. Tirapazamine (TPZ) therapy also requires hypoxia circumstance. The MTM nanosystem combined with TPZ can significantly kill tumour cells and inhibit metastasis in vivo and in vitro. We also tested the biological safety of the treatment. In this study, we overcame the EPR defects via the MTM nanosystem, which can realize acute targeted delivery to the tumour site, lactate depletion, promoted reactive oxygen species (ROS) induction, and enhanced the effect of TPZ, demonstrating a potential synergistic combination of cancer therapy with better efficacy and biosafety.

Research Article Issue
CaCO3-MnSiOx hybrid particles to enable CO2-mediated combinational tumor therapy
Nano Research 2022, 15 (9): 8281-8290
Published: 14 June 2022
Downloads:84

Nanocatalysts mediated reactive oxygen species (ROS) based therapy has been exploited as an alternative therapeutic modality of tumor with high specificity and minimal side effects. However, the treatment outcome is limited by the efficiency of local catalytic reaction. Herein, we report a novel type of core–shell hybrid nanoparticles (CaCO3@MS), consisting of CaCO3 and MnSiOx, for synergistic tumor inhibition combining enhanced catalytic effect and calcium overload. In this system, MnSiOx serves as catalysts with glutathione (GSH) responsive Mn2+ ions release functionality. CaCO3 nanoparticles play three important roles, including carbon dioxide (CO2) donor, pH modulator, and Ca2+ overload agent. It is found that the CaCO3 nanoparticles can induce CO2 production and pH increase in acidic tumor environment, both of which promote Mn2+ mediated ROS generation. And simultaneous release of Ca2+ ions from CaCO3 triggers calcium overload in tumor, which functions collaboratively with excessive ROS to induce cancer cell apoptosis. The results demonstrate that after treatment with CaCO3@MS, a remarkable tumor inhibition was achieved both in vitro and in vivo, while no clear toxic effect was observed. This study has therefore provided a feasible effective approach to improve catalytic therapeutic efficacy by an “exogenous CO2 delivery” strategy for combinational tumor therapy.

Research Article Issue
ATP-responsive hollow nanocapsules for DOX/GOx delivery to enable tumor inhibition with suppressed P-glycoprotein
Nano Research 2021, 14 (1): 222-231
Published: 05 January 2021
Downloads:34

Multidrug resistance (MDR) restricts chemotherapy efficacy due to P-glycoprotein (P-gp) mediated drug efflux, whereas current approaches to suppressing P-gp expression suffer from intrinsic challenges, such as low transfection, high toxicity and poor specificity. Here, hollow ferric-tannic acid complex nanocapsules (HFe-TA), which can be effectively degraded by the reaction with adenosine triphosphate (ATP), are synthesized for the delivery of glucose oxidase (GOx) and doxorubicin (DOX) for tumor treatment. The findings indicate that the intracellular ATP is significantly decreased due to the combined effect of HFe-TA degradation and GOx-mediated glucose consumption. Along with this ATP down-regulation, P-gp expression of tumor cells is suppressed remarkably, which in turn promotes the intracellular accumulation and anticancer efficacy of DOX. In addition, the production of •OH by Fe ions released from HFe-TA is promoted by the by-products of the oxidation of glucose process by GOx. In consequence, HFe-TA nanocapsules loaded with DOX and GOx enable significant inhibition effect to tumors both in vitro and in vivo due to the synergistic effect of cascade reactions. This study has therefore provided an alternative therapeutic platform for effective tumor inhibition with the potential in overcoming intrinsic MDR.

Research Article Issue
Mesoporous silica decorated with platinum nanoparticles for drug delivery and synergistic electrodynamic-chemotherapy
Nano Research 2020, 13 (8): 2209-2215
Published: 05 August 2020
Downloads:61

Electrodynamic therapy (EDT) is a conceptually new cancer treatment approach recently proposed by our group. During EDT, the electro-driven catalytic reaction would occur on the surface of platinum nanoparticles (PtNPs) to produce reactive oxygen species (ROS) under the direct current (DC) or square-wave alternating current (AC) electric field. To further extend the potential of EDT, we hereby designed mesoporous silica-based nanocomposites decorated with PtNPs and loaded with anticancer drug doxorubicin (DOX) for synergistic electrodynamic-chemotherapy. Such silica-based nanocomposites could enable homogenous killing of large-sized tumors (over 500 mm3) and realize remarkable tumor destruction efficacy at a relatively low quantity of electricity. To our best knowledge, this is the first study to combine EDT and chemotherapy to develop a synergetic nanoplatform, openning a new dimension for the design of other EDT-based anticancer strategies.

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