Progress on the pathological tissue microenvironment barrier-modulated nanomedicine

Han, Han; Liu, Xing; Chen, B; Liu, Yang; Zhou, Tian‐Jiao; Wang, Yi; Zhang, Lingfeng; Li, Ling; Cho, Chong‐Su; Jiang, Hu‐Lin

doi:10.1016/j.addr.2023.115051

Advanced Drug Delivery Reviews

2023

DOI: 10.1016/j.addr.2023.115051

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Progress on the pathological tissue microenvironment barrier-modulated nanomedicine

Han Han

Xing Liu

B Chen

et al.

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2024

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Cited by 13 publications

References 285 publications

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Dual Barrier‐Penetrating Inhaled Nanoparticles for Enhanced Idiopathic Pulmonary Fibrosis Therapy

Yang,

Han,

Tang

et al. 2024

Adv Funct Materials

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Idiopathic pulmonary fibrosis (IPF) is an age‐related pulmonary interstitial disease with unclear etiology that poses a serious threat to human health. IPF interventions in clinical settings mainly involve oral medications, such as nintedanib (NIN), which exhibit limited accumulation in the lungs and neglect the epithelial micro‐environment. Inhalation is an efficient route for the treatment of pulmonary diseases. However, the mucus barrier in the trachea and the extracellular matrix (ECM) barrier in the interstitium are the two main obstacles to inhaled therapeutic agent delivery. Therefore, in this study, dual barrier‐penetrating inhaled liposomes (AN‐TR) are constructed utilizing tris‐(2‐carboxyethyl)‐phosphine (TCEP) and l‐arginine to penetrate the mucus and ECM barriers, respectively. This approach facilitates the thorough and uniform distribution of NIN and navitoclax (ABT‐263) across all five lung lobes. Furthermore, ABT‐263 can remove the senescent epithelial cells in the trachea and alveoli, thereby improving the efficiency of NIN for IPF treatment. This study suggests dual barrier‐penetrating inhaled liposomes as efficient noninvasive vehicles for first‐line clinical medications to improve the efficacy of IPF treatment.

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Dual Barrier‐Penetrating Inhaled Nanoparticles for Enhanced Idiopathic Pulmonary Fibrosis Therapy

Yang,

Han,

Tang

et al. 2024

Adv Funct Materials

Self Cite

View full text Add to dashboard Cite

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Modulating Fibrotic Mechanical Microenvironment for Idiopathic Pulmonary Fibrosis Therapy

Li,

Lin,

Han

et al. 2024

Advanced Materials

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Idiopathic pulmonary fibrosis (IPF) is exacerbated by injurious mechanical forces that destabilize the pulmonary mechanical microenvironment homeostasis, leading to alveolar dysfunction and exacerbating disease severity. However, given the inherent mechanosensitivity of fibrotic lungs, where type II alveolar epithelial cells (AEC IIs) are subjected to persistent stretching and overactivated myofibroblasts experience malignant interactions during mechanotransduction, it becomes imperative to develop effective strategies to modulate the pulmonary mechanical microenvironment. Herein, cyclo (RGDfC) peptide‐decorated zeolitic imidazolate framework‐8 nanoparticles (named ZDFPR NPs) are constructed to target and repair the aberrant mechanical force levels in pathological lungs. Specifically, reduces mechanical tension in AEC IIs by pH‐responsive ZDFPR NPs that release zinc ions and 7, 8‐dihydroxyflavone to promote alveolar repair and differentiation. Meanwhile, malignant interactions between myofibroblast contractility and extracellular matrix stiffness during mechanotransduction are disrupted by the fasudil inhibition ROCK signaling pathway. The results show that ZDFPR NPs successfully restored pulmonary mechanical homeostasis and terminated the fibrosis process in bleomycin‐induced fibrotic mice. This study not only presents a promising strategy for modulating pulmonary mechanical microenvironment but also pioneers a novel avenue for IPF treatment.

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Programmable Morphology‐Adaptive Peptide Nanoassembly for Enhanced Catalytic Therapy

Zhang,

Song,

et al. 2024

Advanced Materials

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Nanocatalytic therapy holds significant promise in cancer treatment by exploiting the high oxidative stress within tumor cells. However, efficiently delivering nanocatalytic agents to tumor tissues and maximizing their catalytic activity in situ remain critical challenges. Morphology‐adaptive delivery systems, capable of adjusting their physical form in response to physiological conditions, offer unique spatiotemporal control for navigating complex biological environments like the tumor microenvironment. While designing systems that undergo multiple shape transformations often involves complex stimuli‐responsive mechanisms, making programmable responses through simple designs highly desirable yet challenging. Here, FeFKC, an innovative adaptive material is introduced that achieves multi‐step morphological transformations at the tissue level and amplifies catalytic activity through a straightforward design. As the microenvironmental pH decreases during drug delivery, FeFKC dynamically transitions between single chains, nanoparticles, and nanofibers. This programmable shape‐shifting facilitates deep tumor penetration, enhanced cellular uptake, and lysosomal escape, significantly improving its catalytic efficiency in nanocatalytic tumor therapy. In vivo studies demonstrate that FeFKC achieves impressive tumor suppression efficacy of up to 95% without notable biosafety concerns. The findings highlight the potential of adaptive nanomaterials with programmable shape‐transforming capabilities to overcome biological barriers and enhance catalytic therapy, opening new avenues for cancer treatment and other complex diseases.

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Progress on the pathological tissue microenvironment barrier-modulated nanomedicine

Cited by 13 publications

References 285 publications

Dual Barrier‐Penetrating Inhaled Nanoparticles for Enhanced Idiopathic Pulmonary Fibrosis Therapy

Dual Barrier‐Penetrating Inhaled Nanoparticles for Enhanced Idiopathic Pulmonary Fibrosis Therapy

Modulating Fibrotic Mechanical Microenvironment for Idiopathic Pulmonary Fibrosis Therapy

Programmable Morphology‐Adaptive Peptide Nanoassembly for Enhanced Catalytic Therapy

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