Abstract
To design a new type of antitumor nanodrug carrier with good biocompatibility, a drug delivery system with a 2.19% drug-loading rate, measured by high-performance liquid chromatography (HPLC), was prepared by membrane hydration using a mixed polymer: Pluronic® F-127, which binds folic acid (FA), Pluronic® F-68 and triptolide (TPL) (FA-F-127/F-68-TPL). As a control, another drug delivery system based on a single polymer (FA-F-127-TPL) with a 1.90% drug-loading rate was prepared by substituting F-68 with F-127. The average particle sizes of FA-F-127/F-68-TPL and FA-F-127-TPL measured by a particle size analyzer were 30.7 nm and 31.6 nm, respectively. Their morphology was observed by atomic force microscopy (AFM). The results showed that FA-F-127-TPL self-assembled into nanomicelles, whereas FA-F-127/F-68-TPL self-assembled into nanogels. An MTT assay showed that a very low concentration of FA-F-127/F-68-TPL or FA-F-127-TPL could significantly inhibit the proliferation of multidrug-resistant (MDR) breast cancer cells (MCF-7/ADR cells) and induce cell death. The effects were signifcantly different from those of free TPL (P < 0.01). Using the fuorescent probe Nile red (Nr) as the drug model, FA-F-127/F-68-Nr nanogels and FA-F-127-Nr nanomicelles were prepared and then incubated with human hepatocarcinoma (HepG2) and MCF-7/ADR cells, and the fluorescence intensity in the cells was measured by a multifunctional microplate reader. The results indicated that both FA-F-127/F-68-Nr and FA-F-127-Nr had sustained release in the cells, but HepG2 and MCF-7/ADR cells exhibited significantly higher endocytosis of FA-F-127/F-68-Nr than that of FA-F-127-Nr (P < 0.01). A nude mice transplanted tumor model was prepared to monitor FA-F-127/F-68-Nr in the tumor tissue and organs by whole-body fluorescent imaging. The results showed that FA-F-127/F-68-Nr targeted tumor tissues. The prepared nanogels had small particle size, were easy to swallow, exhibited slow release property, targeted tumor cells, and could improve the antitumor effects of TPL; hence, they are ideal carriers for low-dose antineoplastic drugs.
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Funded by the National Natural Science Foundation of Hubei Province (No. 2014CFB306), the National Natural Science Foundation of China(No. 51772233), the National Key Research and Development Program of China (No. 2016YFC1101605) and the Science and Technology Support Program of Hubei Province (No. 2015BAA085)
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Yin, M., Su, Z., Cui, B. et al. A New Type of Nanogel Carrier based on Mixed Pluronic Loaded with Low-Dose Antitumor Drugs. J. Wuhan Univ. Technol.-Mat. Sci. Edit. 34, 960–967 (2019). https://doi.org/10.1007/s11595-019-2144-5
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DOI: https://doi.org/10.1007/s11595-019-2144-5