Dual-pH responsive micelle platform for co-delivery of axitinib and doxorubicin
Abstract
While the complicated pathogenesis of cancer results in limited therapeutic efficacy of current mono-drug treatment, combination therapy by multiple drugs is becoming increasingly attractive due to the decreased side effects and synergistic anti-cancer activities. The recently emerging modality is the co-delivery of traditional chemotherapeutics and anti-angiogenesis agents. Although nanocarriers are frequently utilized for the co-delivery of different drugs, there are still concerns regarding their implementations. Most of the nanocarriers cannot release drugs separately into their different targeted sites of action. Therefore, we have developed a micellar platform for the co-delivery of an antiangiogenesis agent, axitinib (AXI) and a DNA intercalator, doxorubicin (DOX). Our results showed that this cross-linked micelle (DA-CM) could release AXI and DOX in tumor extracellular environment and intracellular lysosome compartments, respectively, in response to the dual pH stimulus. Notably, DA-CM exhibited remarkably improved tumor accumulation, cell internalization, tumor spheroids penetration and cytotoxicity. Ultimately, DA-CM reduced the number of immature vessels within xenograft tumors, demonstrating an effective antiangiogenesis effect. Meanwhile, they inhibited tumor growth by 88%. Our co-delivery micellar system with the dual-pH responsive feature might hold great promises for the combinatory cancer therapy.
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The advanced nanomicelle system led to effective tumor targeting with inhibition of the tumor development by 88%.
“The advanced nanomicelle system led to effective tumor targeting with inhibition of the tumor development by 88%.”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [160]
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- Authors
- Xu, X., Li, L., Zhou, Z., Sun, W., & Huang, Y.
- Affiliations
- Sichuan University (CN)
- Corresponding author
- Huang, Yuan
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 507
- Issue
- 1-2
- Pages
- 50-60
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W2346987617
- Cited by
- 41
- References
- 49
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 3
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81473167)
- Ministry of Education of the People's Republic of China (2013018111001)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- axitinib, doxorubicin, co-delivery, cross-linked micelles, angiogenesis inhibition, DNA intercalators, tumor extracellular pH, tumor spheroids, tumor vascularization, combination cancer therapy, tumor accumulation
- MeSH terms
- Axitinib, Cell Survival, Cells, Cultured, Doxorubicin, Humans, Hydrogen-Ion Concentration, Imidazoles, Indazoles, Micelles, Polymers, Drug Delivery Systems, Angiogenesis Inhibitors, Xenograft Model Antitumor Assays, Drug Liberation
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