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J Control Release. 2017 Aug 10;259:203-211. doi: 10.1016/j.jconrel.2016.10.029. Epub 2016 Oct 28.

Andrographolide-loaded polymerized phenylboronic acid nanoconstruct for stimuli-responsive chemotherapy.

Author information

1
Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
2
Center for Self-assembly and Complexity, Institute of Basic Science (IBS), Pohang 37673, Republic of Korea.
3
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
4
Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea; Center for Self-assembly and Complexity, Institute of Basic Science (IBS), Pohang 37673, Republic of Korea; School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea. Electronic address: wjkim@postech.ac.kr.

Abstract

Along with the successful discovery of paclitaxel as an anticancer drug, natural products have drawn great attention in drug discovery. Recently, andrographolide (AND) from Andrographis paniculata was reported to provide several benefits, including an anticancer effect. However, the extremely low solubility of the compound in an aqueous medium was an obstacle to overcome for the systemic administration and clinical application of AND. Based on our previous report, we formulated a water-soluble nanoconstruct by forming a boronic ester between the cis-1,3-diol of AND with hydrophilically polymerized phenylboronic acid (pPBA). The release of loaded AND was controlled by intracellular conditions, specifically, by low pH and high ATP concentrations, due to the pH- and diol-dependent affinity of the boronic ester. Because of the intrinsic property of the PBA moiety, the pPBA-AND nanoconstruct exhibited an excellent tumor targeting ability both in vitro and in vivo. Finally, a significant inhibition of tumor growth was observed in vivo. Taken together, our strategy, which is based on the formulation of a soluble nanoconstruct using hydrophilically polymerized PBA and a cis-diol, is plausible and provides a delivery system for a wide variety of chemotherapeutics. This strategy has applications not only in cancer therapy but also broader fields such as anti-inflammation or immunotherapy.

KEYWORDS:

Andrographolide; Boronic ester chemistry; Drug delivery; Phenylboronic acid; Tumor targeting

PMID:
27984106
DOI:
10.1016/j.jconrel.2016.10.029
[Indexed for MEDLINE]

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