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Abstract Photodynamic therapy (PDT) has been showing great potential in cancer treatment. However, the efficacy of PDT is always limited by the intrinsic hypoxic tumor microenvironment (TME) and the low accumulation efficiency of ...
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Abstract Photodynamic therapy (PDT) has been showing great potential in cancer treatment. However, the efficacy of PDT is always limited by the intrinsic hypoxic tumor microenvironment (TME) and the low accumulation efficiency of photosensitizers in tumors. To address the issue, a multifunctional hollow multilayer nanoplatform (H‐MnO2@TPyP@Bro)?comprising manganese dioxide, porphyrin (TPyP) and bromelain (Bro), is developed for enhanced photodynamic therapy. MnO2 catalyzes the intracellular hydrogen peroxide (H2O2) to produce oxygen (O2), reversing the hypoxic TME in vivo. The generated O2 is converted into singlet oxygen (1O2) by the TPyP shell under near‐infrared light, which can inhibit tumor proliferation. Meanwhile, the Bro can digest collagen in the extracellular matrix around the tumor, and can promote the accumulation of H‐MnO2@TPyP@Bro in the deeper tumor tissue, further improving the therapeutic effect of PDT. In addition, MnO2 can react with the overexpressed glutathione in TME to release Mn2+. Consequently, Mn2+ not only induces chemo‐dynamic therapy based on Fenton reaction by converting H2O2 into hydroxyl radicals, but also activates the Mn2+‐based magnetic resonance imaging. Therefore, the developed H‐MnO2@TPyP@Bro nanoplatform can effectively modulate the unfavorable TME and overcome the limitations of conventional PDT for cancer diagnostic and therapeutic.
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? 2022 Elsevier Inc.Ferrocene and its derivatives have great potential for biomedical applications, but few related studies have been reported. In this study, copper ions and ferrocene derivatives were used for the first time to c...
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? 2022 Elsevier Inc.Ferrocene and its derivatives have great potential for biomedical applications, but few related studies have been reported. In this study, copper ions and ferrocene derivatives were used for the first time to construct the ferrocene-based nanoparticles (Cu-Fc) with a hydrated particle size of approximately 220 nm. Their good photothermal conversion properties were verified in vitro and in vivo for the first time, indicating that they could be used as a novel photothermal agent for tumor treatment. In addition, the nanoparticles exhibited efficient Fenton effect under weakly acidic conditions, indicating that they can generate hydroxyl radicals ([rad]OH) to kill tumors in the weakly acidic environment of the tumor-specific microenvironment. More importantly, the nanoparticles can deplete glutathione (GSH), thus further enhancing Fenton effect-mediated chemodynamic therapy (CDT). Multifunctional ferrocene-based nanoparticles (DOX@Cu-Fc) were obtained after loading the chemotherapeutic drug doxorubicin hydrochloride (DOX). The results of in vitro and in vivo experiments showed that DOX@Cu-Fc could enhance tumor treatment by the combination of chemo/CDT/photothermal therapy (PTT).
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Given the diversity, complexity, and heterogeneity of persistent tumors, traditional nanoscale monotherapeutic systems suffer from dissatisfactory curative efficiency with incidence of metastasis or relapse. In parallel, the trend...
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Given the diversity, complexity, and heterogeneity of persistent tumors, traditional nanoscale monotherapeutic systems suffer from dissatisfactory curative efficiency with incidence of metastasis or relapse. In parallel, the trend of clinical research on the basis of nanomedicines has increasingly shifted from monotherapy toward combinatorial therapy for admirable synergetic performances. In this regard, cutting-edge nanomedicines harnessing photothermal-chemodynamic bimodal therapy (PTT/CDT) have opened up a highly-efficient and relatively-safe cancer theranostic paradigm. Still, the integration of PTT/CDT functional units into one nanomedicine remains a herculean but meaningful task to achieve notable super-additive effects. This review aims to elucidate underlying synergistic interactions of PTT/CDT and highlight intriguing designs of nanomedicines for PTT/CDT including nanomaterial selection, performance optimization, multimodal therapy, visualization strategies, and targeting strategies. Furthermore, an outlook on further improvements of PTT/CDT is provided, emphasizing significant scientific issues that require remediation for clinical translation.
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? 2023 Elsevier B.V.Increasing the formation of reactive oxygen species (ROS) and reducing the elimination of ROS are the two main objectives in the development of novel inorganic sonosensitizers for use in sonodynamic therapy (SD...
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? 2023 Elsevier B.V.Increasing the formation of reactive oxygen species (ROS) and reducing the elimination of ROS are the two main objectives in the development of novel inorganic sonosensitizers for use in sonodynamic therapy (SDT). Therefore, BTO–Pd–MnO2–HA nanocomplexes with targeted tumor cells and degradable oxygen-producing shells were designed as piezoelectric sonosensitizers for enhancing SDT. The deposition of palladium particles (Pd NPs) leads to the formation of Schottky junctions, promoting the separation of electron–hole pairs and thereby increasing the efficiency of toxic ROS generation in SDT. The tumor microenvironment (TME) triggers the degradation of MnO2, and the released Mn2+ ions catalyze the generation of hydroxyl radicals (?OH) from H2O2 through a Fenton-like reaction. BTO–Pd–MnO2–HA can continuously consume glutathione (GSH) and generate O2, thereby improving the efficiency of SDT and chemodynamic therapy (CDT). A multistep enhanced SDT process mediated by the piezoelectric sonosensitizers BTO–Pd–MnO2–HA was designed, targeted by hyaluronic acid (HA), activated by decomposition in TME, and amplified by deposition of Pd. This procedure not only presents a new alternative for the improvement of sonosensitizers but also widens the application of piezoelectric nanomaterials in biomedicine.
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Cancer has been one of the most common life-threatening diseases for a long time. Traditional cancer therapies such as surgery, chemotherapy (CT), and radiotherapy (RT) have limited effects due to drug resistance, unsatisfactory t...
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Cancer has been one of the most common life-threatening diseases for a long time. Traditional cancer therapies such as surgery, chemotherapy (CT), and radiotherapy (RT) have limited effects due to drug resistance, unsatisfactory treatment efficiency, and side effects. In recent years, photodynamic therapy (PDT), photothermal therapy (PTT), and chemodynamic therapy (CDT) have been utilized for cancer treatment owing to their high selectivity, minor resistance, and minimal toxicity. Accumulating evidence has demonstrated that selective delivery of drugs to specific subcellular organelles can significantly enhance the efficiency of cancer therapy. Mitochondria-targeting therapeutic strategies are promising for cancer therapy, which is attributed to the essential role of mitochondria in the regulation of cancer cell apoptosis, metabolism, and more vulnerable to hyperthermia and oxidative damage. Herein, the rational design, functionalization, and applications of diverse mitochondria-targeting units, involving organic phosphine/sulfur salts, quaternary ammonium (QA) salts, peptides, transition-metal complexes, guanidinium or bisguanidinium, as well as mitochondria-targeting cancer therapies including PDT, PTT, CDT, and others are summarized. This review aims to furnish researchers with deep insights and hints in the design and applications of novel mitochondria-targeting agents for cancer therapy.
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Starvation therapy (ST) and chemodynamic therapy (CDT) are emerging tumor therapy methods in recent years. In this study, a simple approach was reported to prepare MoS2 and glucose oxidase (GOx)-containing sodium alginate (ALG)-Fe...
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Starvation therapy (ST) and chemodynamic therapy (CDT) are emerging tumor therapy methods in recent years. In this study, a simple approach was reported to prepare MoS2 and glucose oxidase (GOx)-containing sodium alginate (ALG)-Fe3+ (MAF) hydrogel. In the hydrogel, there exists an enzymatic reaction to consume glucose to form hydrogen peroxide (H2O2), and a redox reaction between Fe3+ and MoS2 to form Fe2+ and MoO42-. The formed Fe2+ could be oxidized to Fe3+, which reacts with MAF hydrogel again to continuously produce Fe2+. The consumption of glucose resulted in an obvious tumor ST. Moreover, the produced Fe2+ induced a Fenton reaction to enable the persistent conversion of H2O2 to cytotoxic hydroxyl radicals (center dot OH) for the CDT of tumors. Together with the high photothermal transforming capability of MoS2, the hydrogel was used for the combined tumor photothermal therapy (PIT), ST, and CDT. This work provides a window for the safe use of enzymes for achieving high tumor therapeutic efficacy.
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Catalytic cancer therapy based on nanozymes has recently attracted much interest. However, the types of the current nanozymes are limited and their efficiency is usually compromised and not sustainable in the tumor microenvironmen...
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Catalytic cancer therapy based on nanozymes has recently attracted much interest. However, the types of the current nanozymes are limited and their efficiency is usually compromised and not sustainable in the tumor microenvironment (TME). Therefore, combination therapy involving additional therapeutics is often necessary and the resulting complication may jeopardize the practical feasibility. Herein, an unprecedented "all-in-one" Fe3O4/Ag/Bi2MoO6 nanoparticle (FAB NP) is rationally devised to achieve synergistic chemodynamic, photodynamic, photothermal therapy with guidance by magnetic resonance, photoacoustic, and photothermal imaging. Based on its manifold nanozyme activities (mimicking peroxidase, catalase, superoxide dismutase, glutathione oxidase) and photodynamic property, cascaded nanocatalytic reactions are enabled and sustained in TME for outstanding therapeutic outcomes. The working mechanisms underlying the intraparticulate interactions, sustainability, and self-replenishment arising from the coupling between the nanocatalytic reactions and nanozyme activities are carefully revealed, providing new insights into the design of novel nanozymes for nanocatalytic therapy with high efficiency, good specificity, and low side effects.
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In recent years, multifunctional hydrogel nanoplatforms for the synergistic treatment of tumors have received a great deal of attention. Here, we prepared an iron/zirconium/polydopamine/carboxymethyl chitosan hydrogel with Fenton ...
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In recent years, multifunctional hydrogel nanoplatforms for the synergistic treatment of tumors have received a great deal of attention. Here, we prepared an iron/zirconium/polydopamine/carboxymethyl chitosan hydrogel with Fenton and photothermal effects, promising for future use in the field of synergistic therapy and prevention of tumor recurrence. The iron (Fe)-zirconium (Zr)@ polydopamine (PDA) nanoparticles were synthesized by a simple one-pot hydrothermal method using iron (III) chloride hexahydrate (FeCl3?6H2O), zirconium tetrachloride (ZrCl4), and dopamine, followed by activation of the carboxyl group of carboxymethyl chitosan (CMCS) using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC)/N(4)-hydroxycytidine (NHS). Finally, the Fe-Zr@PDA nanoparticles and the activated CMCS were mixed to form a hydrogel. On the one side, Fe ions can use hydrogen peroxide (H2O2) which is rich in the tumor microenvironment (TME) to produce toxic hydroxyl radicals (?OH) and kill tumor cells, and Zr can also enhance the Fenton effect; on the other side, the excellent photothermal conversion efficiency of the incorporated PDA is used to kill tumor cells under the irradiation of near-infrared light. The ability of Fe-Zr@PDA@CMCS hydrogel to produce ?OH and the ability of photothermal conversion were verified in vitro, and swelling and degradation experiments confirmed the effective release and good degradation of this hydrogel in an acidic environment. The multifunctional hydrogel is biologically safe at both cellular and animal levels. Therefore, this hydrogel has a wide range of applications in the synergistic treatment of tumors and the prevention of recurrence.
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The therapeutic effect of chemodynamic therapy (CDT) is significantly restricted by the stern reaction conditions and slow reaction rate of the Fenton reaction (pH 3-4). Herein, we report an ultrasmall trimetallic (Pd, Cu, and Fe)...
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The therapeutic effect of chemodynamic therapy (CDT) is significantly restricted by the stern reaction conditions and slow reaction rate of the Fenton reaction (pH 3-4). Herein, we report an ultrasmall trimetallic (Pd, Cu, and Fe) alloy nanozyme (PCF-a NEs) possessing dynamic active-site synergism, thus exhibiting a cascade glutathione peroxidase and peroxidase (POD) mimicking activities in circumneutral pH. PCF-a NEs exhibit photothermally augmented POD property and high photothermal conversion efficiency (62%) for synergistic tumor cell apoptosis. In addition, ultrasound can also enhance the mass transfer at active catalytic sites of PCF-a NEs, in turn accelerating Fenton-like reaction for tumor-specific CDT. This work provides a strategy for engineering alloy nanozymes in a bioinspired way for the amplification of intratumor reactive oxygen species in response to external stimuli, demonstrating enhanced efficiency for the inhibition of tumor growth in vitro and in vivo.
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Abstract Chemodynamic therapy (CDT) based on Fenton‐like reaction is often limited by the tumor microenvironment (TME), which has insufficient hydrogen peroxide, and single CDT treatment is often less efficacious. To overcome the...
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Abstract Chemodynamic therapy (CDT) based on Fenton‐like reaction is often limited by the tumor microenvironment (TME), which has insufficient hydrogen peroxide, and single CDT treatment is often less efficacious. To overcome these limitations, a hydrogel‐based system is designed to enhance the redox stress (EOH) by loading the composite nanomaterial Cu‐Hemin‐Au, into the agarose hydrogels. The hydrogels can reach the tumor site upon intratumoral injection, and then coagulate and stay for extended period. Once irradiated with near‐infrared light, the Cu‐Hemin‐Au act as a photothermal agent to convert the light energy into heat, and the EOH gradually heated up and softened, releasing the Cu‐Hemin‐Au residing in it to achieve photothermal therapy (PTT). Benefiting from the glucose oxidase (GOx)‐like activity of the Au nanoparticles, glucose in the tumor cells is largely consumed, and hydrogen peroxide (H2O2) is generated in situ, and then Cu‐Hemin‐Au react with sufficient H2O2 to generate a large amount of reactive oxygen species, which promote the complete inhibition of tumor growth in mice during the treatment cycle. The hydrogel system for the synergistic enhancement of oxidative stress achieves good PTT/CDT synergy, providing a novel inspiration for the next generation of hydrogels for application in antitumor therapy.
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