Jul 2026· Small· pp.
e74654
· 0 citations· 57 references
Medicine
TL;DR
A multifunctional nanoplatform by integrating a type I aggregation-induced emission photosensitizer (NTI) with a Cu-based nanozyme (MOF-Cu) enables efficient ROS generation, precise mitochondria targeting, and real-time fluorescence imaging, allowing more effective activation of ferroptosis and cuproptosis.
Abstract
Cancer therapeutic strategies centered on synergistic ferroptosis and cuproptosis have attracted considerable interest. However, current approaches predominantly relying on Fe and Cu sources face limitations including single mode of reactive oxygen species (ROS) production, poor organelle targeting, and lack of imaging capabilities. Herein, we developed a multifunctional nanoplatform, NMC NPs, by integrating a type I aggregation-induced emission photosensitizer (NTI) with a Cu-based nanozyme (MOF-Cu). This design enables efficient ROS generation, precise mitochondria targeting, and real-time fluorescence imaging, allowing more effective activation of ferroptosis and cuproptosis. Upon cellular uptake, MOF-Cu framework dissociates and releases NTI, which selectively accumulates in mitochondria. Under 635 nm laser irradiation, NTI generates type I ROS, triggering lipid peroxidation and activating ferroptosis. Simultaneously, MOF-Cu nanozyme exerts dual peroxidase-like and glutathione peroxidase-like activities, catalyzing H2O2 into hydroxyl radicals while depleting glutathione and releasing Cu+ ions, further promoting ferroptosis. Notably, the released Cu+ ions further disrupt mitochondrial function, induce dihydrolipoamide S-acetyltransferase aggregation, and activate cuproptosis. The synergistic action efficiently enhances immunogenic cell death. In vivo studies confirmed the potent antitumor efficacy of NMC NPs with minimal side effect. This study provides new insights into the cooperative regulation of metal-dependent cell death and advances the design of integrated theranostic nanoplatforms.
Cerium molybdate-doped polyaniline nanoparticles are developed to enable a synergistic combination of photothermal therapy (PTT) and CDT, thereby triggering immunogenic cell death (ICD) and enhancing antitumor immunity and presenting a robust nanoplatform integrating chemodynamic and photothermal therapies for potent cancer immunotherapy.
Yulin Kuang, Cheng Lu, Bolan Yu et al.· Bioactive Materials· 0 citations
Photodynamic therapy (PDT) efficacy is severely compromised by tumor hypoxia and the scarcity of efficient type-I photosensitizers, necessitating multimodal therapeutic strategies. Herein, we report a porphyrin-Cu (II) covalent organic framework (TBCOF) with intrinsic bifunctional photodynamic and chemodynamic activities. Sequential DOX encapsulation and hyaluronic acid (HA) surface functionalization afford HA-TBCOF@DOX, a tumor-targeted nanoplatform integrating four synergistic therapeutic modalities. Under 660 nm laser irradiation, the nanoplatform generates ROS signatures consistent with both type-I and type-II pathways for PDT, while the intrinsic Cu2+ centers are proposed to catalyze a Fenton-like reaction consistent with •OH generation for CDT. Concurrently, observations of O2 evolution suggest catalase-like activity that may decompose endogenous H2O2 into O2, alleviating hypoxia and potentiating oxygen-dependent PDT. Efficient photothermal conversion and pH-triggered DOX release contribute to photothermal and chemotherapeutic effects, respectively, while HA-mediated CD44 targeting enhances cellular uptake and therapeutic specificity. In vitro and in vivo studies demonstrate that laser-activated HA-TBCOF@DOX effectively suppresses tumor growth, induces apoptosis, and exhibits no apparent systemic toxicity under the tested experimental conditions. This work establishes a multifunctional COF-based nanoplatform that addresses PDT limitations observed in this study by integrating intrinsic PDT and CDT, providing a robust strategy for synergistic multimodal cancer therapy.
Yongjie Mo, Jie Hou, Hong-Li Li et al.· Materials Today Bio· 0 citations
A structurally reinforced ternary redox-cycling nanoreactor that integrates Zr4⁺-stabilized zeolitic imidazolate framework-8 with redox-active Cu/Mn centers and ultrasmall Au nanodots achieves sustained ROS amplification, iron-homeostasis remodeling, and enhanced tumor-selective ferroptosis, offering a promising therapeutic strategy for TNBC.
Wan-mei Zhou, Zixin Wang, Chengdong Nie et al.· International journal of pha...· 0 citations
Triple-negative breast cancer (TNBC) presents formidable treatment barriers due to dysfunctional vasculature and an immunosuppressive microenvironment. To address these challenges, we engineered a bioinspired near-infrared (NIR)-responsive copper–polyphenol nanoplatform, SCP, to implement a NIR-triggered “bridge-and-attack” therapeutic strategy. This nanoassembly was constructed through the coordination of salvianolic acid B (SAB) with copper ions and further stabilized by a polydopamine (PDA) shell. Upon NIR irradiation, SAB and Cu2+ were co-released from SCP, enabling simultaneous vascular remodeling and tumor cell killing. The released SAB promoted vascular normalization, increasing pericyte coverage to 51.6% and alleviating tumor hypoxia, thereby facilitating intratumoral penetration and immune-cell infiltration. Meanwhile, released Cu2+, together with PDA-mediated photothermal activation, induced cuproptosis and immunogenic cell death (ICD). This combined remodeling of the tumor microenvironment enhanced CD8+ T cell infiltration and achieved a tumor inhibition rate of 88.5% in 4T1 tumor-bearing mice with favorable systemic biosafety. Overall, this interfacial nanomaterial design integrates vascular normalization, photothermal-enhanced cuproptosis, and immunotherapy, providing a promising materials-based strategy for TNBC treatment.
Porphyrin bimetallic metal-organic frameworks (BMOFs) have promising applications in photodynamic therapy (PDT) and chemodynamic therapy (CDT) for tumor therapy. However, their therapeutic effect is restricted by the insufficient reactive oxygen species generated by BMOFs. Herein, a nanobomb, Fe-TCPP(Mn)/DOX/PEG/Apt-M (FTMDPA), with pH-responsive properties, was designed for fluorescence imaging-guided triple-action tumor annihilation. First, a novel Fe/Mn porphyrin BMOF, Fe-TCPP(Mn) (FTM), was assembled by a solvothermal method to achieve enhanced tumor therapy through ROS amplification. Under 660 nm laser irradiation, TCPP(Mn) could act as a photosensitizer to activate PDT. Significantly, TCPP(Mn) and Fe3+ exhibit peroxidase-like and Fenton-like activities, catalyzing the generation of •OH from H2O2, which effectively amplifies CDT. Besides, FTMDPA exhibits pH-responsive DOX release capability, which could achieve chemotherapy (CHT), and could efficiently accumulate at the tumor site with the aid of an aptamer. Importantly, FTMDPA exhibits fluorescence imaging, which has potential applications in detection and image-guided precision therapy. Therefore, the designed nanobomb integrates targeted delivery, pH responsiveness, fluorescence imaging, and amplified PDT-CDT-CHT triple-action tumor annihilation into a single system, providing a promising strategy for tumor diagnosis and treatment.
Photodynamic therapy (PDT) has garnered considerable attention due to its remarkable spatiotemporal selectivity, minimal invasiveness, and low potential for drug resistance. However, traditional photosensitizers (PSs) applied in PDT usually suffer from aggregation-caused quenching (ACQ) effect, the difficulty in overcoming tumor hypoxic resistance, single and inefficient photochemical mechanism of action (MoA), poor cancer targeting ability, etc. In this work, three novel dinuclear Ru(II) complexes (Ru1-Ru3) with aggregation-induced emission (AIE) activity were developed and their structure-property relationships were systematically investigated. Among them, Ru1 can efficiently generate both type I and type II reactive oxygen species (ROS). Notably, Ru1 is also able to potently photo-oxidize reduced nicotinamide adenine dinucleotide (NADH) with a record-breaking turnover frequency (TOF) value of approximately 2688 h-1. By further loading of Ru1 in bovine serum albumin (BSA) with tumor targeting ability, the resultant Ru1@BSA could selectively accumulate in tumor tissues and efficiently inhibit tumor growth by photo-inducing ferroptosis and immunogenic cell death (ICD) on a 4T1 tumor-bearing mouse model. This work highlights dinuclear Ru(II) AIE photosensitizers as a promising platform for multimodal photodynamic cancer therapy.
Yu Shi, Xiaoang Liu, Xuwen Da et al.· Journal of Inorganic Biochem...· 0 citations
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