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ACS Applied Materials & Interfaces · 2019 · IF 8.456

Cell Membrane-Coated Porphyrin Metal–Organic Frameworks for Cancer Cell Targeting and O2-Evolving Photodynamic Therapy

Di Zhang,Zhongju Ye,Lin Wei,Haibin Luo,Lehui Xiao

Photodynamic therapy (PDT) has attracted great attention as an alternative tumor treatment method. Unfortunately, it suffers from some limitations like poor targeting capability and insufficient therapeutic efficiency caused by tumor hypoxia. In this work, we introduce a novel O2-evolving PDT nanoparticle for homologous cancer cell targeting as well as dual-mode imaging [i.e., magnetic resonance imaging (MRI) and fluorescence imaging]. Specifically, the nanostructure consists of a MnO2 nanosheet-coated metal–organic framework core and cancer cell membrane shell (defined as CM-MMNPs). The MnO2 layer displays H+ and H2O2 responsiveness, which can produce O2 to enhance O2-mediated singlet oxygen (1O2) generation for PDT. Moreover, the resulted Mn2+ can also be used as an optimal MRI contrast agent. The introduction of cell membrane and membrane proteins endow the CM-MMNPs with good stability and integrity in the process of cellular endocytosis, as well as strong homologous cell-targeting ability. This multifunctional nanoparticle has the potential to overcome the hypoxia of cancer cells in PDT, and provides a new paradigm for tumor targeting, detection, and therapy, which is promising for biomedical applications in the future.

研究领域: 生物医学工程 · 癌症研究 · 纳米技术 · 诊疗学
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Biomaterials Science · 2020 ·Vol. 8 ·期 14 ·3844-3855 · IF 6.183

Hollow ferric-tannic acid nanocapsules with sustained O2 and ROS induction for synergistic tumor therapy

Huimin Zhu,Guodong Cao,Chu Qiang,YiKe Fu,Yulian Wu,Xiang Li,Gaorong Han

Nanoparticles presenting promoted catalytic activity, oxygen induction and loading capability are in high demand for effective synergistic tumor therapy. Herein, ferric-tannic acid complex nanocapsules with fine hollow microstructure (HFe-TA) are synthesized and loaded with a photosensitizer (indocyanine green, ICG) for synergistic tumor therapy. In acidic environment, ICG@HFe-TA decomposes and releases Fe3+ ions, TA and ICG molecules. Fe3+, with low catalytic activity, is effectively converted into highly catalytic Fe2+ by the reductant TA, enabling promoted efficacy of ˙OH induction. More importantly, the ROS (1O2) induction by ICG is significantly enhanced under 808 nm laser irradiation due to the O2 byproduct of Fe3+/Fe2+ conversion. In consequence, the ICG@HFe-TA nanoparticles exhibit considerable in vitro and in vivo tumor inhibition owing to the combined effect of ˙OH and 1O2 induced intracellularly. This study has therefore demonstrated a potential platform enabling combined photodynamic and chemodynamic therapy with high efficacy.

研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 生物化学
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Materials Today · 2022 · IF 26.943

Surface-engineered chlorella alleviated hypoxic tumor microenvironment for enhanced chemotherapy and immunotherapy of first-line drugs

Cheng Gao,Cheryl H.T. Kwong,Qingfu Wang,Hiotong Kam,Jianwen Wei,Qian Chen,Jian Zhang,Simon M.Y. Lee,Dayong Gu,Ruibing Wang

A large number of chemotherapeutic and immunotherapeutic agents have been shown to be less effective when exposed to a hypoxic solid tumor. The tumor hypoxia microenvironment contributes to multidrug resistance and immunosuppression, and current delivery of oxygen or enzyme to alleviate hypoxic microenvironment is often limited by the oxygen supplying capacity of material-based carriers and short window of oxygen production. Herein, macrophage membrane coated chlorella (M-Chl) is constructed for targeted delivery to the solid tumor and sustainable oxygen production via photosynthesis, which provides a new general strategy to overcome tumor hypoxia and improve chemotherapy and immunotherapy. The camouflaged strategy via macrophage membrane coating enhances tumor accumulation and retention of Chl due to the inflammatory homing effects of macrophage membrane, which contributes to long term oxygen production for at least 6 days with one dose of Chl, resulting in efficient downregulation of tumor HIF-1α. In vivo antitumor therapy in mice shows that M-Chl enhances the chemotherapeutic efficacy of doxorubicin via inhibiting hypoxia-mediated overexpression of drug efflux proteins, and also improves the poor immunotherapeutic performance of T cell activation agent, anti-CTLA-4 antibody, via downregulating hypoxia-mediated immunosuppressive proteins. Thus, M-Chl may serve as an important adjuvant for enhancing the therapeutic efficacy of clinical antitumor drugs against solid tumors.

研究领域: 癌症研究 · 药学 · 生物技术 · 免疫学
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Advanced Healthcare Materials · 2024 · IF 10

Self-Produced O2 CNs-Based Nanocarriers of DNA Hydrophobization Strategy Triggers Photodynamic and Mitochondrial-Derived Ferroptosis for Hepatocellular Carcinoma Combined Treatment

Ming-Xuan Liu,Yan-Chao Liu,Yu-Ting Cai,Ying-Ying Gu,Ya-Qi Zhu,Nan Zhang,Wei-Zhong Zhu,Yong-Hong Liu,Lei Yu,Qi-Tao Zhang,Xiao-Ling Zhang

Hypoxia can aggravate tumor occurrence, development, invasion, and metastasis, and greatly inhibit the photodynamic therapy (PDT) effect. Herein, carbon nitride (CNs)-based DNA and photosensitizer co-delivery systems (BPSCNs) with oxygen-producing functions are developed to address this problem. Selenide glucose (Seglu) is used as the dopant to prepare red/NIR-active CNs (SegluCNs). The tumor-targeting unit Bio-PEG 2000 is utilized to construct BPSCNs nanoparticles through esterification reactions. Furthermore, DNA hydrophobization is realized via mixing P53 gene with a positively charged mitochondrial-targeted near-infrared (NIR) emitting photosensitizer (MTTPY), which is encapsulated in non-cationic BPSCNs for synergistic delivery. Ester bonds in BPSCNs@MTTPY-P53 complexes can be disrupted by lipase in the liver to facilitate P53 release, upregulated P53 expression, and promoted HIF-1α degradation in mitochondria. In addition, the oxygen produced by the complexes improved the hypoxic microenvironment of hepatocellular carcinoma (HCC), synergistically downregulated HIF-1α expression in mitochondria, promoted mitochondrial-derived ferroptosis and enhanced the PDT effect of the MTTPY unit. Both in vivo and in vitro experiments indicated that the transfected P53-DNA, produced O 2 and ROS by these complexes synergistically led to mitochondrial-derived ferroptosis in hepatoma cells through the HIF-1α/SLC7A11 pathway, and completely avoiding PDT resistance caused by hypoxia, exerting a significant therapeutic role in HCC treatment.

CAS / MDL: 2301-80-6 291279-14-6
研究领域: 癌症生物学 · 药学 · 生物医学工程 · 分子生物学 · 治疗学
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Applied Materials Today · 2024 · IF 7.2

Ti3C2Tx MXene nanosheet-based drug delivery/cascaded enzyme system for combination cancer therapy and anti-inflammation

Qianqian Qiao,Jinyu Wang,Bingjiao Li,Yuhao Guo,Tao Liao,Ziqiang Xu,Ying Kuang,Cao Li

Photothermal therapy (PTT)-based combination therapy is an effective approach to cancer treatment. However, there is a possibility of tumor development due to the inflammation caused by PTT. In addition, hyperthermia can cause damage to normal tissues. This work reported a drug delivery/cascade enzyme system based on Ti 3 C 2 T x MXene nanosheets. Ultra-small, degradable mesoporous silica nanoparticles (DS-MSN) were prepared to load phloretin (Phl), which has anti-inflammatory, antioxidant, and anticancer properties. Subsequently, glucose oxidase (GOx) was adsorbed on the surface of DS-MSN. The nanoparticles were then modified on Ti 3 C 2 T x MXene nanosheets and finally treated with polyethylene glycol (PEG) to obtain the multifunctional system named Ti 3 C 2 T x -Phl@DS-MSN-GOx-PEG (TPDMGP). The high near-infrared photothermal conversion efficiency of Ti 3 C 2 T x made it suitable for PTT. GOx and Ti 3 C 2 T x formed a cascade enzyme system inside cancer cells: Ti 3 C 2 T x exhibited catalase (CAT)-like activity that decomposed intracellular hydrogen peroxide (H 2 O 2 ) into O 2 , which was provided to GOx for enhanced starvation therapy. GOx in the presence of O 2 produces H 2 O 2 , for the oxygen production of Ti 3 C 2 T x . Meanwhile, DS-MSN could be degraded in the reducing environment inside cancer cells as it contains disulfide bonds in its backbone, thus releasing Phl for chemotherapy. Such a combination therapy strategy could achieve a satisfactory therapeutic outcome by low-temperature PTT while evading normal tissue damage by high temperature. The anti-inflammatory effects of both Ti 3 C 2 T x and Phl enabled TPDMGP to eliminate the inflammation caused by PTT via the scavenging of reactive oxygen species (ROS). The multifunctional system is expected to generate new paradigms for cancer PTT.

CAS / MDL: 919-30-2
研究领域: 纳米技术 · 癌症治疗 · 药物递送系统 · 酶工程 · 材料科学
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