Tumor vasculature normalization by orally fed erlotinib to modulate the tumor microenvironment for enhanced cancer nanomedicine and immunotherapy
Abstract
The abnormal tumor vasculature is one of key reasons that lead to the limited tumor perfusion as well as hypoxic and immunosuppressive tumor microenvironment (TME). Herein, we uncover that by normalizing the tumor vasculature with erlotinib, a specific inhibitor of epidermal growth factor receptor (EGFR), the tumor perfusion and tumor oxygenation statuses in different types of tumors including murine breast tumors, colorectal tumors, and squamous cell carcinoma tumors, could be remarkably enhanced. As the results, the tumor uptake of drug-loaded nanoparticles as well as their interstitial penetration within the tumor would be greatly increased for mice pre-treated with erlotinib at the oral feeding dose of 50 mg/kg, leading to remarkably improved chemotherapeutic efficacy of nanomedicine. On the other hand, owing to the erlotinib-induced normalization of tumor vasculatures, the relieved hypoxic state in the three different types of tumors could alter the immunosuppressive TME into immunosupportive. Such an effect together with the increased tumor retention of anti-PDL1 antibody, a clinically approved checkpoint blockade agent, finally contributes to the greatly improved tumor inhibition effect in cancer immunotherapy. Therefore, our work presents a general yet effective strategy using a clinical drug to enhance the efficacies of cancer nanomedicine and immunotherapy by normalizing tumor vasculatures and modulating TME.
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Combination therapy of erlotinib and HAS-PTX produced significant tumor size reduction compared to HAS-PTX alone.
“A significant tumor size reduction was observed in models with combination therapy of erlotinib and has-PTX in comparison to the HAS-PTX group alone.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [27]
Higher vascular normalization resulted in higher distribution of HAS-PTX to the tumor site.
“A higher vascular normalization resulted in a higher distribution of hasHSA-PTX to the tumor site.”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [27]
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“This improved the accumulation of human serum albumin-bound paclitaxel (HAS-PTX) in vivo in tumor-bearing mice such as head and neck carcinoma cells (SCC7), colon carcinoma cells (CT26), and breast cancer cells (4T1) [27].”
Background
- Authors
- Chen, Q., Xu, L., Chen, J., Yang, Z., Liang, C., Yang, Y., & Liu, Z.
- Affiliations
- Soochow University (CN)
- University of Macau (MO)
- Corresponding author
- Liu, Zhuang
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 148
- Pages
- 69-80
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2760277446
- Cited by
- 104
- References
- 55
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 10 · 2023: 12 · 2022: 13 · 2021: 9 · 2020: 20 · 2019: 18 · 2018: 10
- FWCI
- 4.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Basic Research Programs of China (2016YFA0201200)
- National Natural Science Foundation of China (51525203, 31300824)
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- tumor vasculature normalization, erlotinib, EGFR inhibition, tumor microenvironment, tumor hypoxia, tumor perfusion, tumor oxygenation, oral drug delivery, nanoparticle drug delivery, cancer nanomedicine, cancer immunotherapy, PD-L1 inhibitors, tumor immunosuppression, breast cancer, colorectal cancer, squamous cell carcinoma
- MeSH terms
- Erlotinib Hydrochloride, Administration, Oral, Animals, Antibodies, Antibodies, Monoclonal, Breast Neoplasms, Carcinoma, Squamous Cell, Female, Humans, Immunotherapy, Mice, Inbred BALB C, Mice, Nude, Neoplasm Transplantation, Permeability, Colorectal Neoplasms, Cell Line, Tumor, Nanomedicine, Nanoparticles, Tumor Microenvironment, B7-H1 Antigen, Antibodies, Monoclonal, Humanized, Heterografts, ErbB Receptors
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