Advanced Healthcare Materials
·
2026
·
IF 11
Hong Jiang,Qin-Xie Xie,Tianzhao Tian,Qingqing Yang,Peipei Qian,Jia-Yi Liu,Wending Yan,Shengfeng Huang,Cui Shao,Wei Yi,Yifa Chen,Xu-Jia Hong
The complex tumor microenvironment (TME), characterized by coexisting normoxic and hypoxic regions, demands oxygen-adaptive nanomedicines for multimodal therapy. Herein, GTPZ is presented, an oxygen-adaptive covalent organic framework (COF)-based nanoplatform that can achieve quadruple-modal synergistic therapy through the integration of chemodynamic therapy (CDT), photothermal therapy (PTT), Type I/II photodynamic therapy (PDT), and hypoxia-activated chemotherapy. Remarkably, GTPZ exhibits a record-high photothermal conversion efficiency of 72% among COF-based nanomedicines, enabling spatiotemporal control over hypoxia-activated tirapazamine (TPZ) release to generate cytotoxic radicals. Besides, GTPZ dynamically adapts to oxygen gradients by activating Type II PDT in normoxia and switching to Type I PDT in hypoxia, with phototherapy-induced oxygen depletion amplifying TPZ activation, exhibiting high oxygen-adaptive ability. In MCF-7 models, GTPZ achieves high tumor suppression through synergistic lipid peroxidation, cell cycle arrest, and ferroptosis. This work provides a paradigm for designing intelligent nanomedicines capable of dynamically adapting to TME.
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高影响因子
Nano-Micro Letters
·
2021
·Vol. 14
·期 1
·1-21
·
IF 16.419
Zhang Xiaoge,Cheng Lili,Lu Yao,Tang Junjie,Lv Qijun,Chen Xiaomei,Chen You,Liu Jie
Gene-engineering tumor cell membrane with CD47 over-expression is achieved to improve the macrophage-mediated phagocytosis of tumor cells by blocking CD47 immune checkpoint.
A cascade-enzyme nanoreactor combining tumor enzyme dynamic therapy, phototherapy, and deoxygenation-activated chemotherapy is proposed.
Glucose oxidase and chloroperoxidase can generate sufficient HClO to kill normoxic tumor cells, and tirapazamine can be subsequently activated to kill hypoxic tumor cells.
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PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-18
·
IF 12.6
An Jie,Chu Kaile,Li Xirong,Ma Huizhu,Zhou Qin,Niu Chenliang,Gao Jie,Lv Junping,Cao Jianbo,Zhang XinYu,Zhou Haitao,Wang Hongliang,Li Min,Wu Zhifang,Li Sijin
Radionuclide therapy and chemotherapy are effective for pancreatic cancer, yet their efficacy is often limited by tumor hypoxia. In this study, manganese porphyrin (MnTTP) and tirapazamine (TPZ) were encapsulated in polylactic-co-glycolic acid (PLGA) spheres, which were subsequently coated with polydopamine to label the radionuclide 131 I, forming a theranostic nanoplatform. The nanoplatform demonstrated excellent biocompatibility, stable labeling efficiency, and dual-modal MRI/SPECT imaging capabilities. The nanoplatform generated reactive oxygen species (ROS) under ultrasound(US) activation, in combination with the β-rays emitted by 131 I, synergistically eradicate tumor cells and exacerbate hypoxia in the tumor microenvironment. Furthermore, TPZ was activated to produce toxic free radicals under hypoxic conditions, enabling a synergistic therapeutic approach that combined radionuclide therapy and sonodynamic therapy. This approach effectively inhibited tumor stem cell formation and enhanced anti-tumor efficacy. Additionally, the nanoplatform’s metabolism in vivo and the therapeutic effect were monitored in real-time under MRI/SPECT dual-modality imaging. This therapeutic strategy offers a promising solution for overcoming tumor hypoxia and achieving efficient combination therapy for tumors.
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ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jialiang Zheng,Zhenhang Lin,Xi Li,Fenglin Miao,Tuerhong Maimaitiming,Yuan Ma,Zhao Wang,Yilai Gao,Zhe Xi,Aobo Zhuang,Ruyi Zhang,Yingxue Cheng,Xiaogang Xia,Yue Wang,Yan Huang,Xu Kong,Fanghong Luo,Huichen Li,Chundong Yu,Wengang Li
Embolotherapy is an effective antitumor method, which essentially blocks the oxygen supply and induces hypoxia to treat tumors; however, traditional practices demand high expertise and harbor risks of complications. This study presents a mesoporous polydopamine-based (MPDA) drug delivery platform modified by engineered fusion proteins, which can specifically embolize tumor blood vessels and deliver the hypoxia-activated prodrug tirapazamine (TPZ). The fusion protein consists of an affibody targeting HER-2, a substrate for MMP-2, an RGD tripeptide, and a truncated tissue factor (tTF), which is then connected to MPDA loaded with TPZ. This nanodrug can actively target HER-2, interact with MMP-2 in the tumor microenvironment (TME), and embolize blood vessels; then, under TME acidic circumstances, MPDA releases TPZ, which is activated by hypoxia aggravated by embolization, and kills tumors. This embolization strategy, which is activated only under specific conditions, is extremely safe, and it compensates for the inadequacies of conventional embolization therapy, while also addressing the issue of hypoxia deficiency in hypoxia-activated prodrug therapy.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Kunpeng Lin,Shaochen Wang,Shuling Yu,Wen Si,Miaojie Yang,Ningning Xu,Yu Liu,Yan Zheng,Shuang Zhao,Jiahua Shi,Jintao Yuan
Porphyrins are popular photosensitizers for photodynamic therapy of diseases. However, the poor water solution and short absorption wavelengths of porphyrins limit their clinical application. In this work, a novel worm-like porphyrin covalent organic framework (Por-COF) with excellent dispersibility and near-infrared absorption was prepared via a facile method. First, a pH-responsive macromolecule was prepared using Schiff base bonds between porphyrin and terephthalaldehyde, and the spatial arrangement of macromolecules was controlled to prepare Por-COF. Second, the hypoxia-responsive drug tirapazamine (TPZ) and tumor-targeted hyaluronic acid (HA) were loaded to Por-COF through the electrostatic effect to prepare a multifunction nanomedicine (Por-COF@TPZ/HA) that could simultaneously produce abundant reactive oxygen species and high temperature via808 nm laser irradiation. TPZ was cascaded for the synergistic therapy of cancers. In vitro cytotoxicity showed that the inhibition rate of cell activity in the Por-COF@TPZ/HA + Laser group was 1.2 times higher than that in the Por-COF/HA + Laser group. In vivo experiments also demonstrated that the aggravated tumor hypoxia caused by photodynamic therapy could activate TPZ to achieve high-efficiency chemotherapy. Combined photodynamic–photothermal therapy and chemotherapy had an outstanding synergistic effect. This work provides a promising method for Por-COF preparation and a feasible strategy for the synergistic therapy of cancers.
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