Cited by 41Nanoparticle-Based Drug DeliveryRNA Interference and Gene DeliveryNanoplatforms for cancer theranostics

Dual-pH responsive micelle platform for co-delivery of axitinib and doxorubicin

Xu, Xiuli, Li, Lian, Zhou, Zhou, Sun, Wei, Huang, Yuan·2016·International Journal of Pharmaceutics

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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Crossref · 10.1016/j.ijpharm.2016.04.060

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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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