Vascular and extracellular matrix remodeling by physical approaches to improve drug delivery at the tumor site

Gouarderes, Sara; Mingotaud, Anne‐Françoise; Vicendo, Patricia; Gibot, Laure

doi:10.1080/17425247.2020.1814735

Cited by 20 publications

(10 citation statements)

References 188 publications

(235 reference statements)

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“…In accordance with previous studies 40 , 41 , we found that the combined PDT could remodel the tumor microenvironment by significantly reducing the amounts of cancer associated fibroblasts (CAFs) and the density of extracellular matrix proteins, such as collagen and fibronectin (Supplementary Fig. 18 ).…”

Section: Resultssupporting

confidence: 92%

Dissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging

et al. 2022

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Efficient delivery of payload to intracellular targets has been identified as the central principle for nanomedicine development, while the extracellular targets are equally important for cancer treatment. Notably, the contribution of extracellularly distributed nanoparticles to therapeutic outcome is far from being understood. Herein, we develop a pH/light dual-responsive monochromatic ratiometric imaging nanoparticle (MRIN), which functions through sequentially lighting up the intracellular and extracellular fluorescence signals by acidic endocytic pH and near-infrared light. Enabled by MRIN nanotechnology, we accurately quantify the extracellular and intracellular distribution of nanoparticles in several tumor models, which account for 65–80% and 20–35% of total tumor exposure, respectively. Given that the majority of nanoparticles are trapped in extracellular regions, we successfully dissect the contribution of extracellularly distributed nanophotosensitizer to therapeutic efficacy, thereby maximize the treatment outcome. Our study provides key strategies to precisely quantify nanocarrier microdistribtion and engineer multifunctional nanomedicines for efficient theranostics.

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Section: Resultssupporting

confidence: 92%

Dissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging

et al. 2022

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“…Combined PDT inhibited tumor metastasis by remodeling the tumor microenvironment. In accordance with previous studies 40,41 , we found that the combined PDT could remodel the tumor microenvironment by significantly reducing the amounts of cancer associated fibroblasts (CAFs) and the density of extracellular matrix proteins, such as collagen and fibronectin (Supplementary Fig. 12).…”

Section: Quantitative Imaging Of Extracellular and Intracellular Distribution Of Nanoparticles In Different Tumorssupporting

confidence: 91%

Dissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging

Yan

Chen

Yin

et al. 2021

Preprint

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Efficient delivery of payload to intracellular targets has been identified as the central principle for nanomedicine development, while the extracellular targets are equally important for cancer treatment. Notably, the contribution of extracellularly distributed nanoparticles to therapeutic outcome is far from being understood. Herein, we develop a pH/light dual-responsive monochromatic ratiometric imaging nanoparticle (MRIN), which functions through sequentially lighting up the intracellular and extracellular fluorescence signals by acidic endocytic pH and near-infrared light. Enabled by MRIN nanotechnology, we accurately quantify the extracellular and intracellular distribution of nanoparticles in several tumor models, which account for 65-80% and 20-35% of total tumor exposure, respectively. Given that the majority of nanoparticles are trapped in extracellular regions, we successfully dissect the contribution of extracellularly distributed nanophotosensitizer to therapeutic efficacy, thereby maximize the treatment outcome. Our study provides key strategies to precisely quantify nanocarrier microdistribtion and engineer multifunctional nanomedicines for efficient theranostics.

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“…The mobility of drugs in penetrating the extracellular matrix is also limited by cell-cell adhesion, high interstitial fluid pressure, lack of convection, drug metabolism, and binding (9,40). Recent data suggest that inefficient delivery of antineoplastic drugs in the tumor environment is a novel and important contributor to chemoresistance (19,20,(41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

Long Distance From Microvessel to Cancer Cell Predicts Poor Prognosis in Non-Small Cell Lung Cancer Patients

et al. 2021

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BackgroundBlood supply, which is crucial for nutrition and drug delivery, was determined by microvessel density as well as the diffusion distance between vessels and cancer cells. Therefore, we evaluated the distance from microvessels to cancer cells (Dmvcc) and its role in the prognosis of non-small cell lung cancer (NSCLC) patients.MethodsPatients with primary NSCLC were retrospectively analyzed. The tumor samples were immunochemically stained with CD31 to visualize the microvessels. The Dmvcc was defined as the mean distance from each microvessel to its nearest cancer cell in the “hot-spot” of an individual patient. The patients were stratified into short- and long-distance groups using five strategies, including dichotomy by the median value, optimal cutoff, trichotomy, quartation and per-10 µm increase. The correlation between the Dmvcc and survival was evaluated by using univariate and multivariate analyses with various Dmvcc strategies.ResultsIn total, 100 patients were analyzed. The median value of Dmvcc was 13.1 μm (ranged, 1.6 to 269.7 μm; mean value, 24.4 ± 33.5 μm). The optimal cutoff value of Dmvcc for predicting survival outcome was 20 μm. Dmvcc was significantly related to overall survival (OS) with all the five categories (p = 0.001–0.000004) and progression-free survival (PFS) categorized by optimal cutoff value (p = 0.024), trichotomy (p = 0.041) and per-10 µm increase (p = 0.040) after adjusting for other factors. Patients with longer Dmvcc (≥20 μm) were observed to have poor survival outcomes (OS: HR = 13.5, 95CI: 4.42–41.18, p = 0.000005; PFS: 3.26, 95CI: 1.56–6.81, p = 0.002). A high Dmvcc per-10 µm was associated with a significantly increased risk of cancer-related death and progression by 98% (p = 0.0001) and 30% (p = 0.044), respectively.ConclusionThe NSCLC tissues had varying distances from microvessels to cancer cells, and long distances were strongly associated with poor survival.

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Vascular and extracellular matrix remodeling by physical approaches to improve drug delivery at the tumor site

Cited by 20 publications

References 188 publications

Dissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging

Dissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging

Dissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging

Long Distance From Microvessel to Cancer Cell Predicts Poor Prognosis in Non-Small Cell Lung Cancer Patients

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