Journal
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 16, Issue 6, Pages 794-805Publisher
SHENYANG PHARMACEUTICAL UNIV
DOI: 10.1016/j.ajps.2021.08.002
Keywords
Self-delivery system; Chondroitin sulfate; Tumor metastasis; Multiphase
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Funding
- Major Projects of the National Natural Science Foundation of China [81974499]
- Sichuan Science and Technology Program [2018RZ0136]
- Sichuan Veterinary Medicine and Drug innovation Group of China Agricultural Research System [SCCXTD-2020-18]
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The synthesized CT NPs can effectively inhibit cancer metastasis and provide excellent therapeutic effects on solid tumors and metastases.
Metastasis is closely related to the high mortality of cancer patients, which is regulated by multiple signaling pathways. Hence, multiphase blocking of this biological process is beneficial for cancer treatments. Herein, we establish a multifunctional self-delivering system by synthesizing D-alpha-tocopheryl succinates (TOS)-conjugated chondroitin sulfate (CS) (CT NPs), which both serve as nanocarrier and antimetastatic agent that affects different phases of the metastatic cascade. TOS as the hydrophobic segment of CT NPs can inhibit the secretion of matrix metalloproteinase-9, while the hydrophilic segment CS targets B16F10 cells through CD44 receptors and reduces the interaction between tumor cells and platelets. The results show that CT NPs are able to inhibit metastasis successfully both in vitro and in vivo by interfering the multiphase of the metastatic cascade. Following encapsulating chemotherapeutic drug doxorubicin (DOX), the obtained micelles CT/DOX efficiently suppress both primary-tumor growth and metastases in B16F10 bearing mice. As a result, the rationally designed multifunctional NPs composing of biocompatible materials provide excellent therapeutic effects on solid tumors and metastases. (C) 2021 Shenyang Pharmaceutical University. Published by Elsevier B.V.
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