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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS · 2022 · IF 5.589

A biotin-modified and H2O2-activatable theranostic nanoplatform for enhanced photothermal and chemical combination cancer therapy

Chuanjiang Jian,Ying Wang,Huijun Liu,Zongning Yin

Although synergistic effects of photothermal therapy (PTT) and chemotherapy for cancer have been extensively investigated in previous studies, more potential strategies need to be exploited to alleviate severe adverse effects. In this study, a biotin-modified and activatable nanotheranostic system is developed. This system (BPSP/DOX-CyBA) composed of H 2 O 2 -sensitive thioketal (TK) linker, hydrophilic biotin-decorated polyethylene glycol (PEG) segment, hydrophobic polycaprolactone (PCL) segment, could self-assemble into (99 ± 1.3) nm nanoparticles and co-deliver H 2 O 2 -triggered photosensitizer CyBA and cytotoxic drugs DOX to tumor site. In vitro , DOX and CyBA could release rapidly from nanoparticles, CyBA accumulation in the mitochondria causes mitochondrial damage, leading to mitochondrial dysfunctions,while rising the level of ROS in B16F10 cells, and further to promote the micells to trigger release. CyBA could be activated into CyOH and the photothermal therapy was turn “off” into “on”. In BPSP/DOX-CyBA group, the local temperature within tumor reached 50 °C and cell apoptosis rate reached 68.6% under Laser irradiation (650 nm, 1 W/cm 2 ). Fluorescence microscopy and flow cytometry analysis further demonstrated the better uptake efficiency on B16F10 cells with biotin decoration. In a mice B16F10 tumor model, the group with co-delivery CyBA and DOX had the best tumor retention effect, the maximal local temperature increasement and the minimum tumor growth with negligible side effects, suggesting the potential of BPSP/DOX-CyBA nanopalteform that synergistic photothermal therapy and chemotherapy and mitochondria damage as an effective melanoma treatment strategy.

研究领域: 肿瘤学 · 药剂学 · 生物医学工程
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ACS Nano · 2023 · IF 17.1

Regulating the H2O2 Activation Pathway on a Well-Defined CeO2 Nanozyme Allows the Entire Steering of Its Specificity between Associated Enzymatic Reactions

Bo Yuan,Zicong Tan,Qiang Guo,Xiutong Shen,Chao Zhao,Jian Lin Chen,Yung-Kang Peng

Nanozymes are promising alternatives to natural enzymes, but their use remains limited owing to poor specificity. For example, CeO2 activates H2O2 and displays peroxidase (POD)-like, catalase (CAT)-like, and haloperoxidase (HPO)-like activities. Since they unavoidably compete for H2O2, affecting its utilization in the target application, the precise manipulation of reaction specificity is thus imperative. Herein, we showed that one can simply achieve this by manipulating the H2O2 activation pathway on pristine CeO2 in well-defined shapes. This is because the coordination and electronic structures of Ce sites vary with CeO2 surfaces, wherein the (100) and (111) surfaces display nearly 100% specificity toward POD-/CAT-like and HPO-like activities, respectively. The antibacterial results suggest that the latter surface can well-utilize H2O2 to kill bacteria (cf., the former), which is promising for anti-biofouling applications. This work provides atomic insights into the synthesis of nanozymes with improved activity, reaction specificity, and H2O2 utilization.

CAS / MDL: 143-74-8 54827-17-7
研究领域: 生物化学 · 材料科学 · 纳米医学
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Acta Biomaterialia · 2021 · IF 8.947

A self-assembled nanoplatform based on Ag2S quantum dots and tellurium nanorods for combined chemo-photothermal therapy guided by H2O2-activated near-infrared-II fluorescence imaging

Chao-Qing Li,Meng-Wen Ma,Bin Zhang,Wei Chen,Zhong-Yuan Yin,Xiao-Ting Xie,Xiao-Lin Hou,Yuan-Di Zhao,Bo Liu

A nanoplatform based on Ag 2 S quantum dots (QDs) and tellurium nanorods (TeNRs) was developed for combined chemo-photothermal therapy guided by H 2 O 2 -activated near-infrared (NIR)-II fluorescence imaging. Polypeptide PC 10 AGRD-modified TeNRs and Ag 2 S QDs were co-encapsulated in 4T1 cell membrane to prepare a nanoplatform ( [email protected] ). Ag 2 S QDs and TeNRs in the [email protected] were used as a fluorescence probe and photosensitizer , and a chemotherapeutic prodrug and quenching agent to quench the fluorescence of Ag 2 S QDs, respectively. After the [email protected] was specifically targeted to the tumor site, the TeNRs were dissolved by the high concentration of H 2 O 2 at the tumor site to light up the fluorescence of Ag 2 S QDs for NIR-II fluorescence imaging. In addition, the generated toxic TeO 6 6− molecules decreased ATP production by selective cancer chemotherapy, which is beneficial for photothermal therapy. The elevated temperature due to photothermal therapy in turn promoted the chemical reaction in chemotherapy. In vitro and in vivo toxicity results showed that the [email protected] possesses high biocompatibility. Compared to single photothermal therapy and chemotherapy, the synergistic chemo-photothermal therapy can effectively suppress the growth of 4T1 tumor. This all-in-one nanoplatform provides a boulevard for the combination therapy of tumors guided by NIR-II fluorescence imaging. Statement of significance NIR-II fluorescence imaging shows the characteristics of low tissue absorption, reflection, and scattering, which can greatly reduce the influence of autofluorescence in vivo . However, the non-negligible effect of autofluorescence is still observed in fluorescence imaging in vivo . Therefore, there is an urgent need to develop a strategy of controlled release of fluorescence for accurate imaging and tumor therapy. Here, Ag 2 S quantum dots (QDs) with NIR-II fluorescence emission and good photothermal conversion efficiency are used as a fluorescence probe and photosensitizer, and tellurium nanorods (TeNRs) are used as a chemotherapeutic prodrug and quenching agent to quench the fluorescence of Ag 2 S QDs. This multiple nanoplatform provides an inspiration for the combination therapy of tumor guided by NIR-II fluorescence imaging.

研究领域: 生物医学工程 · 肿瘤学 · 纳米医学 · 影像医学
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Nature Communications · 2021 ·Vol. 12 ·期 1 ·1-15 · IF 14.919

A H2O2-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-II fluorescent imaging

Chen Junjie,Chen Longqi,Wu Yinglong,Fang Yichang,Zeng Fang,Wu Shuizhu,Zhao Yanli

Developing high-quality NIR-II fluorophores (emission in 1000–1700 nm) for in vivo imaging is of great significance. Benzothiadiazole-core fluorophores are an important class of NIR-II dyes, yet ongoing limitations such as aggregation-caused quenching in aqueous milieu and non-activatable response are still major obstacles for their biological applications. Here, we devise an activatable nanoprobe to address these limitations. A molecular probe named BTPE-NO 2 is synthesized by linking a benzothiadiazole core with two tetraphenylene groups serving as hydrophobic molecular rotors, followed by incorporating two nitrophenyloxoacetamide units at both ends of the core as recognition moieties and fluorescence quenchers. An FDA-approved amphiphilic polymer Pluronic F127 is then employed to encapsulate the molecular BTPE-NO 2 to render the nanoprobe BTPE-NO 2 @F127. The pathological levels of H 2 O 2 in the disease sites cleave the nitrophenyloxoacetamide groups and activate the probe, thereby generating strong fluorescent emission (950~1200 nm) and ultrasound signal for multi-mode imaging of inflammatory diseases. The nanoprobe can therefore function as a robust tool for detecting and imaging the disease sites with NIR-II fluorescent and multispectral optoacoustic tomography (MSOT) imaging. Moreover, the three-dimensional MSOT images can be obtained for visualizing and locating the disease foci.

研究领域: 生物医学工程 · 分子影像 · 纳米技术 · 药学
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Advanced Healthcare Materials · 2024 · IF 10

H2O2-Activatable Liposomal Nanobomb Capable of Generating Hypoxia-Irrelevant Alkyl Radicals by Photo-Triggered Cascade Reaction for High-Performance Elimination of Biofilm Bacteria

Ke Yang,Li Wang,Jinyi Chen,Zefeng Wang,Junqin Li,Xi Chen,Shuting Fu,Luo Hai,Le Deng,Dinggeng He

High H 2 O 2 levels are widely present at the infection sites or in the biofilm microenvironment. Herein, hemin with peroxidase-like catalytic activity and its substrate, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), are simultaneously introduced into a liposomal nanoparticle containing thermosensitive 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIBI)-loaded bovine serum albumin (BAG), rationally constructing an H 2 O 2 -activatable liposomal nanobomb (Lipo@BHA) for combating biofilm-associated bacterial infections with high performance. In the presence of H 2 O 2 , hemin can catalyze the conversion of ABTS into its oxidized form (ABTS· + ) with strong near-infrared (NIR) absorption, which produces photonic hyperpyrexia to cause the decomposition of AIBI into oxygen-independent alkyl radicals (·R) and nitrogen (N 2 ) microbubbles. The former not only directly damage bacterial cells but also significantly accelerates the oxidization of ABTS to ABTS· + for augmenting photothermal-triggered generation of ·R. Interestingly, the released N 2 can induce transient cavitation to rupture lysosomal nanoparticle and improve the biofilm permeability, thereby enhancing the antibiofilm effect of Lipo@BHA. The proposed Lipo@BHA exhibits satisfactory multi-mode combination antibacterial properties. Through endogenous H 2 O 2 -activated cascade reaction, Lipo@BHA achieves remarkable hypoxia-irrelevant ·R therapy of biofilm-associated wound infections with low cytotoxicity and good in vivo biosafety. Therefore, this work presents a versatile H 2 O 2 -activatable cascade ·R generation strategy for biofilm-specific therapeutic applications.

研究领域: 纳米技术 · 生物医学工程 · 药学 · 微生物学 · 材料科学
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Nano Research · 2021 ·Vol. 15 ·期 1 ·333-345 · IF 8.897

Cerium oxide nanoparticles-mediated cascade catalytic chemo-photo tumor combination therapy

Hu Zitao,Ding Yin

ROS-based tumor therapy based on nanocatalytic medicine has recently been proposed for its tumor-specificity. However, a safe and highly efficient strategy towards getting high enough ROS to kill the hypoxic cancer cells is still a great challenge. Herein, we report a simple pH/H 2 O 2 -activatable, O 2 -evolving, and ROS regulating doxorubicin (DOX) and indocyanine green (ICG) co-loading PEGylated polyaniline (PANI) coated CeOx@polyacrylic acid (PAA) nanoclusters for highly selective and optimized cancer combination treatment. It can selectively and greatly enhance intracellular O 2 and ROS levels in tumor region, which depends on two-step catalytic properties of nanoceria (Ce 4+ /Ce 3+ = 3.46, neutral surface charge, mostly localize into the cytoplasm, pH 7.4–6.5, catalase-like catalytic agents convert to Ce 4+ /Ce 3+ = 0.58, negative surface charge, mostly localize into the lysosomes, pH 5–4, oxidase-like catalytic agents, triggered by near infrared (NIR) laser irradiation). Furthermore, the protective effect of polyethylene glycol (PEG), PANI, and PAA ensure that the nanoceria can only play the role of catalase under the irradiation of NIR light arrived at the tumor area. Moreover, loading of nanoceria and ICG onto PANI greatly enhanced photo thermal effect of nanoparticles (NPs), which is useful for killing cancer cells by relieving hypoxia and promoting cross-membrane drug delivery to further enhance photodynamic therapy and chemotherapy efficiency. The chemo-photo combination therapies fantastically inhibited tumor growth and prevented tumor recurrence in vivo , suggesting a smart nanotheranostic system to achieve more precise and effective therapies in O 2 -deprived tumor tissue.

研究领域: 纳米技术 · 生物医学工程 · 癌症治疗 · 药学 · 材料科学
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