A mitochondria-targeting self-assembled carrier-free lonidamine nanodrug for redox-activated drug release to enhance cancer chemotherapy

Yang, Ting; Xian-fen, Zhang; Yang, Xing; Liu, Ying; Xiang, Jingjing; Xiang, Chunbai; Liu, Zhongke; Hai, Luo; Huang, Saipeng; Liang, Ruijing; Gong, Ping

doi:10.1039/d2tb02728c

Cited by 6 publications

(3 citation statements)

References 52 publications

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“…To enhance LND's effectiveness, researchers have developed mitochondria-targeted nanocarriers to improve bioavailability and achieve better therapeutic outcomes. Cheng et al [73] developed a mitochondria-targeted prodrug by linking mitochondria-targeting photosensitizer IR780 with sulfonyl aldehyde (TK), forming Cy-TK-LND prodrug. This prodrug selfassembles into carrier-free nanoparticles in an aqueous environment.…”

Section: Targeting Key Enzymesmentioning

confidence: 99%

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Intelligent Delivery Systems in Tumor Metabolism Regulation: Exploring the Path Ahead

Li,

Sun,

Jiang

2023

Advanced Materials

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Cancer metabolism plays multifaceted roles in the initiation and progression of tumors, and interventions in metabolism are considered fundamental approaches for cancer control. Within the vast metabolic networks of tumors, there exist numerous potential therapeutic targets, intricately interconnected with each other and with signaling networks related to immunity, metastasis, drug resistance, and more. Based on the characteristics of the tumor microenvironment, constructing drug delivery systems for multi‐level modulation of the tumor microenvironment is proven as an effective strategy for achieving multidimensional control of cancer. Consequently, this article summarizes several features of tumor metabolism to provide insights into recent advancements in intelligent drug delivery systems for achieving multi‐level regulation of the metabolic microenvironment in cancer, with the aim of offering a novel paradigm for cancer treatment.

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Section: Targeting Key Enzymesmentioning

confidence: 99%

“…Cheng et al. [ 73 ] developed a mitochondria‐targeted prodrug by linking mitochondria‐targeting photosensitizer IR780 with sulfonyl aldehyde (TK), forming Cy‐TK‐LND prodrug. This prodrug self‐assembles into carrier‐free nanoparticles in an aqueous environment.…”

Section: Intelligent Delivery Systems For Regulating Tumor Metabolismmentioning

confidence: 99%

Intelligent Delivery Systems in Tumor Metabolism Regulation: Exploring the Path Ahead

Li,

Sun,

Jiang

2023

Advanced Materials

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“…This suggests a potential mechanism for inducing immunogenic cell death (ICD) by triggering ROS generation in mitochondria. Targeting agents or nano-materials aimed at mitochondria have been reported to enhance ICD effects by precisely controlling mitochondrial ROS production, as demonstrated in previous studies showing that equivalent amounts of ROS generated in mitochondria can induce stronger ICD effects compared to cytoplasmic generation [23,24]. Therefore, endowing agents with mitochondrial targeting capability is crucial for inducing widespread ICD.…”

Section: Introductionmentioning

confidence: 98%

The Conjugate of Rhein–Artesunate for Inducing Immunogenic Cell Death to Prepare Cancer Vaccine and Suppress Tumor Growth

Xu,

Wang,

Huang

2024

Chemistry

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The conjugate of rhein and artesunate have shown promising effects in inducing immunogenic cell death (ICD) and inhibiting tumor growth. Rhein, a natural anthraquinone derivative found in various medicinal plants such as Rheum palmatum, possesses diverse pharmacological properties including anti-inflammatory and anticancer activities. Artesunate, a sesquiterpene lactone extracted from Artemisia annua, exhibits potent antimalarial efficacy and has garnered attention for its potential anticancer properties. Through rational drug design, the conjugation of rhein with artesunate has yielded compounds capable of selectively targeting mitochondria of cancer cells, inducing oxidative stress-mediated ICD, and enhancing the immunogenicity of tumor cells. The conjugate leverages the inherent cytotoxicity of artesunate while incorporating the capability to selectively target the mitochondria of rhein, thereby fostering a special approach to immunotherapy for cancer. Upon accumulation in the mitochondria, these compounds induce the generation of reactive oxygen species (ROS), leading to mitochondrial membrane potential (ΔΨm) reduction and endoplasmic reticulum (ER) stress. Notably, the conjugate exhibits far more potent ICD-inducing properties than their parent compounds. In vivo studies have demonstrated that the vaccine, when treated with the conjugate, effectively suppresses tumor growth.

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Zeolitic Imidazolate Frameworks Based Anticancer Drug Delivery System Associated with Dual Action of Surface Charge and Lewis Base Ligand

Yang,

Tian,

Zhao

et al. 2024

Advanced Therapeutics

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Zeolitic imidazole frameworks (ZIFs), which combine the favorable characteristics of tunable porosity, controlled structure, and facile functionalization, are explored as a novel class of nanocarriers for biomedical applications. In this study, different ZIF materials are investigated, including ZIF‐8, ZIF‐67, ZIF‐90, ZIF‐92, and ZIF‐108, with the same sodalite topology as the adenosine‐5′‐triphosphate (ATP)‐triggered drug delivery systems. Results indicated that ZIF‐90 and ZIF‐108 displayed good biological compatibility and efficiently accumulated in the mitochondria through competitive coordination between the metal nodes of the ZIFs and ATP, suggesting efficient intracellular delivery. With further interactions between these metal ions and ATP, the encapsulated drugs are released from the ZIF nanoparticles, thereby achieving optimal anti‐tumor activity. Through a systematic evaluation of the physicochemical properties of different ZIFs, it demonstrates that the surface charges of ZIFs have a significant impact on the cytotoxicity of cells, whereas the Lewis basicity of imidazole‐based ligands plays an essential role in the competitive coordination between the metal ions and ATP. These findings provide a potential method for screening ZIFs based nanocarriers with minimal toxicity and explain the different delivery efficiencies of these materials with similar topologies.

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A mitochondria-targeting self-assembled carrier-free lonidamine nanodrug for redox-activated drug release to enhance cancer chemotherapy

Abstract: Mitochondria play a vital role in maintaining cellular homeostasis. In recent years, studies have found that mitochondria have an important role in the occurrence and development of tumors, and targeting...

Cited by 6 publications

References 52 publications

Intelligent Delivery Systems in Tumor Metabolism Regulation: Exploring the Path Ahead

Intelligent Delivery Systems in Tumor Metabolism Regulation: Exploring the Path Ahead

The Conjugate of Rhein–Artesunate for Inducing Immunogenic Cell Death to Prepare Cancer Vaccine and Suppress Tumor Growth

Zeolitic Imidazolate Frameworks Based Anticancer Drug Delivery System Associated with Dual Action of Surface Charge and Lewis Base Ligand

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