Normalizing Tumor Vessels To Increase the Enzyme-Induced Retention and Targeting of Gold Nanoparticle for Breast Cancer Imaging and Treatment
Abstract
Abnormal tumor vessels impede the transport and distribution of chemotherapeutics, resulting in low drug concentration at tumor sites and compromised drug efficacy. Normalizing tumor vessels can modulate tumor vascular permeability, alleviate tumor hypoxia, increase blood perfusion, attenuate interstitial fluid pressure, and improve drug delivery. Herein, a novel strategy combining cediranib, a tumor vessel normalizing agent, with an enzyme responsive size-changeable gold nanoparticle (AuNPs-A&C) was developed. In vivo photoacoustic and fluorescence imaging showed that oral pretreatment with 6 mg/kg/day of cediranib for two consecutive days significantly enhanced the retention of AuNPs-A&C in 4T1 tumor. In vivo photoacoustic imaging for hemoglobin (Hb) and oxyhemoglobin (HbO 2 ), Evans blue assay, and immunofluorescence assay showed that cediranib pretreatment markedly increased tumor vascular permeability and tumor oxygenation, while distinctly decreased the tumor microvessel density, demonstrating normalized tumor vessels and favorably altered microenvironment. Additionally, the combination strategy considerably elevated the tumor targeting capacity of different nanoparticle formulations (AuNPs-PEG, AuNPs-A&C), while coadministration of cediranib and AuNPs-A&C achieved prevailing tumor targeting and antitumor efficacy in 4T1 tumor bearing mouse model. In conclusion, we report a novel combined administration strategy to further improve tumor diagnosis and treatment.
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Increase in size led to increased residence time in tumor tissue and improved antitumor effect of size-changeable gold nanoparticles, which increased with coadministration of cediranib.
“The increase in size led to increased residence time in the tumor tissue and improved the antitumor effect of size-changeable gold nanoparticles that increased with the coadministration of cediranib.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [29]
Combination of cediranib (VEGFR TKI) and enzyme-responsive size-changeable gold nanoparticles (from around 40 nm to 300 nm upon enzymatic activity) showed around twofold increase in tumor size suppression in subcutaneous 4T1 tumor model than fixed size nanoparticles.
“Research groups such as Xiao et al. used a combination of cediranib (VEGFR TKI) and enzyme-responsive size changeable gold nanoparticles (from around 40 nm to 300 nm upon enzymatic activity) [29]. The size-changeable gold nanoparticles have shown an around twofold increase in the tumor size suppression in the subcutaneous 4T1 tumor model than the fixed size nanoparticles.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [29]
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- Authors
- Xiao, W., Ruan, S., Yu, W., Wang, R., Hu, C., Liu, R., & Gao, H.
- Affiliations
- Sichuan University (CN)
- Corresponding author
- Gao, Huile
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-09-05
- Volume
- 14
- Issue
- 10
- Pages
- 3489-3498
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- OpenAlex
- W2748893263
- Cited by
- 84
- References
- 53
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 13 · 2021: 12 · 2020: 17 · 2019: 11 · 2018: 11
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31571016, 81402866)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Photoacoustic and Ultrasonic Imaging
- Keywords
- tumor vasculature normalization, cediranib, gold nanoparticles, enzyme-responsive nanoparticles, tumor vascular permeability, tumor hypoxia, tumor microenvironment, 4T1 breast cancer, photoacoustic imaging, fluorescence imaging, tumor targeting, drug delivery, tumor oxygenation, microvessel density
- MeSH terms
- Animals, Antineoplastic Agents, Breast, Breast Neoplasms, Doxorubicin, Female, Gold, Humans, Indoles, Mice, Inbred BALB C, Permeability, Quinazolines, Tissue Distribution, Drug Delivery Systems, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, Metal Nanoparticles, Tumor Microenvironment, Photoacoustic Techniques, Human Umbilical Vein Endothelial Cells, Optical Imaging
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