Anti-angiogenic nano-delivery system promotes tumor vascular normalizing and micro-environment reprogramming in solid tumor

Shen, Ruoyu; Peng, Lijun; Zhou, Wentao; Wang, Ding; Jiang, Qi; Ji, Jian; Hu, Fuqiang; Yuan, Hong

doi:10.1016/j.jconrel.2022.07.015

Cited by 23 publications

(16 citation statements)

References 70 publications

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“…To confirm this view, mice with 231Br brain metastases were treated with an anti‐angiogenic agent vandetanib (ZD6474), an inhibitor of the receptor of vascular endothelial‐derived growth factor. [ 22 ] Neuroserpin and L1CAM recovered after vandetanib treatments (Figure 4d,e). Altogether, these data demonstrate the necessity of combining anti‐angiogenesis with anti‐vascular‐cooption for therapy against brain metastases.…”

Section: Resultsmentioning

confidence: 97%

DH5α Outer Membrane‐Coated Biomimetic Nanocapsules Deliver Drugs to Brain Metastases but not Normal Brain Cells via Targeting GRP94

Zhou

Chen

Zeng

et al. 2023

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Receptor‐mediated vesicular transport has been extensively developed to penetrate the blood‐brain barrier (BBB) and has emerged as a class of powerful brain‐targeting delivery technologies. However, commonly used BBB receptors such as transferrin receptor and low‐density lipoprotein receptor‐related protein 1, are also expressed in normal brain parenchymal cells and can cause drug distribution in normal brain tissues and subsequent neuroinflammation and cognitive impairment. Here, the endoplasmic reticulum residing protein GRP94 is found upregulated and relocated to the cell membrane of both BBB endothelial cells and brain metastatic breast cancer cells (BMBCCs) by preclinical and clinical investigations. Inspired by that Escherichia coli penetrates the BBB via the binding of its outer membrane proteins with GRP94, avirulent DH5α outer membrane protein‐coated nanocapsules (Omp@NCs) are developed to cross the BBB, avert normal brain cells, and target BMBCCs via recognizing GRP94. Embelin (EMB)‐loaded Omp@EMB specifically reduce neuroserpin in BMBCCs, which inhibits vascular cooption growth and induces apoptosis of BMBCCs by restoring plasmin. Omp@EMB plus anti‐angiogenic therapy prolongs the survival of mice with brain metastases. This platform holds the translational potential to maximize therapeutic effects on GRP94‐positive brain diseases.

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Section: Resultsmentioning

confidence: 97%

DH5α Outer Membrane‐Coated Biomimetic Nanocapsules Deliver Drugs to Brain Metastases but not Normal Brain Cells via Targeting GRP94

Zhou

Chen

Zeng

et al. 2023

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“…The cytotoxicity of PEVM to 4T1 and HUVEC was verified by MTT assay (Figure S12). Since the experiment of V@MG promoting the expression of vascular normalization-related proteins and migration of HUVEC has been described in detail in our previous studies, 16 we also evaluated the inhibitory effect of PEVM on VEGF/VEGFRs expression. In short, low dose and slow release of anti-angiogenic drugs from PEVM led to decreased expression of pro-angiogenic proteins VEGFA/ VEGFR2 and increased expression of pro-normalizing protein VEGFR1 in HUVEC (Figure S13).…”

Section: Cell Efficacy Of Pevm Npsmentioning

confidence: 99%

“…Tumor vascular normalization (TVN), with restoration of vascular endothelial junctions, improved pericyte coverage, increased blood perfusion, and reduced leakage; it has been used as a promising approach more effective for anti-tumor therapy. , Preclinical studies have shown that reducing vascular leakiness without pruning increases intratumoral oxygen delivery, , and anti-angiogenic tyrosine kinase inhibitors (TKIs) synergistically enhance anti-tumor effects of PDT in prostate, ovarian, and colorectal tumor models. , Therefore, the combination of TVN and PDT is a promising direction as a desirable anti-tumor strategy. ,,− Our previous research found that the sustained release of low-dose anti-angiogenic TKIs through a nanodrug delivery system can achieve stable and long-term normalization of tumor blood vessels and effectively improve TME hypoxia …”

Section: Introductionmentioning

confidence: 99%

“…2,3,40−42 Our previous research found that the sustained release of lowdose anti-angiogenic TKIs through a nanodrug delivery system can achieve stable and long-term normalization of tumor blood vessels and effectively improve TME hypoxia. 16 In this paper, a composite nanodrug delivery system combining PDT and TVN was rationally designed for promotion of vascular normalization and remodel of TME. We here chose breast cancer as the tumor model, which, as a type of cancer with high incidence and high lethality, has received extensive attention in both preclinical and clinical research because of its high heterogeneity and drug resistance and is a classic solid tumor model.…”

Section: Introductionmentioning

confidence: 99%

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Polymer-Modified Lipid Nanoparticles with Microenvironment-Responsive Graded Release for Amplified Photodynamic Therapy Through Tumor Vascular Normalization

Shen

Wang

et al. 2023

ACS Appl. Nano Mater.

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Photodynamic therapy (PDT) is a promising approach to cancer treatment, but the heterogeneity of the tumor microenvironment (TME) limits its application. Tumor vasculature is thought to be involved in abnormal TME. Therefore, tumor vascular normalization (TVN) is expected to be a strategy to reshape TME. We prepared a graded-release nanodrug combining TVN and PDT, named as PEVM, with the core of lipid nanoparticles for sustained release of anti-angiogenic drugs and the shell of a pH-sensitive polymer linked to a photosensitizer, and evaluated its therapeutic effect on a breast cancer model. We found that PEVM could achieve mutual benefits in both therapeutic effects. TVN not only increased the intratumoral oxygen level as a raw material for PDT, but also activated the anti-tumor immune response, further improving the efficacy of PDT. PEVM showed favorable anti-tumor efficiency and exhibited the potential of combining TVN and PDT.

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“…"Antitumor research is a very active field that has generated a large amount of information on clinical aspects of chemotherapy" [40]. "New therapeutic approaches for the screening of bioactive compounds present in medicinal plants have received increasing attention due to their chemopreventive properties activities" [41].…”

Section: Genus Antitumor Activitymentioning

confidence: 99%

Genus Vernonia (Asteraceae): A Promising Source of Antitumor Agents with Pharmacological Potentials

Gonzatto

Araújo²,

Albuquerque³

2022

AIR

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Antitumor research leads to the development of new molecules that act specifically in tumor cells by blocking or inhibiting their molecular targets. New therapeutic approaches for the screening of bioactive compounds present in medicinal plants have received increasing attention due to their chemopreventive and chemotherapeutic properties. In ethnomedicine, plants of the genus Vernonia (Asteraceae) are widely used and some have shown several and interesting biological activities, including anticancer. This present study aimed to document experimental evidence supporting the claimed ethnomedical uses of Vernonia species for the treatment of various types of cancer and also to confirm the anticancer potential of these plants. The compounds isolated from aqueous and alcoholic extracts, as well as fractions from different parts of Vernonia plants have acted as potential anticancer agents that inhibited the proliferation of various types of human cancer cell lines, including cervical cancer cells, melanoma cells, promyelocytic leucemia cells, breast adenocarcinoma cells, ovarian cancer, liver cancer cell, and human lung cancer cells. Studies have correlated the antitumor activity of Vernonia plants by inducing apoptosis and modulating mitochondrial signaling pathways controlled by NF-κB, Bcl-2 and p53, as well as inducing DNA damage and arresting the cell cycle at the S-phase checkpoint by oxidative stress. In conclusion, Vernonia species act as a promising source for drug development. However, further studies are needed to explore the exact mechanism of action, pharmacokinetics, chronic toxicological studies, safe dose consumption, and possible interactions with other herbs.

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Anti-angiogenic nano-delivery system promotes tumor vascular normalizing and micro-environment reprogramming in solid tumor

Cited by 23 publications

References 70 publications

DH5α Outer Membrane‐Coated Biomimetic Nanocapsules Deliver Drugs to Brain Metastases but not Normal Brain Cells via Targeting GRP94

DH5α Outer Membrane‐Coated Biomimetic Nanocapsules Deliver Drugs to Brain Metastases but not Normal Brain Cells via Targeting GRP94

Polymer-Modified Lipid Nanoparticles with Microenvironment-Responsive Graded Release for Amplified Photodynamic Therapy Through Tumor Vascular Normalization

Genus Vernonia (Asteraceae): A Promising Source of Antitumor Agents with Pharmacological Potentials

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