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21 September 2020 : Animal Research

Construction and Evaluation of Folic Acid-Modified 3-Bromopyruvate Cubosomes

Fangyan Hou1ABCDEF*, Hairong Wang2BF, Yawen Zhang1CF, Na Zhu3ACF, Hao Liu1ACDG, Jianchun Li1ACDEG

DOI: 10.12659/MSM.924620

Med Sci Monit 2020; 26:e924620

Abstract

BACKGROUND: Direct 3-bromopyruvate chemotherapy often causes side effects. We thus aimed to construct and evaluate folic acid-modified 3-bromopyruvate liquid crystalline nanoparticles (3BP-LCNP-FA) and assess their targeted antitumor effects in tumor-bearing nude mice.

MATERIAL AND METHODS: A liquid crystalline nanoparticle formulation was screened, and the structure was characterized using polarizing light- and transmission electron microscopy. The folate target was then synthesized and characterized using differential scanning calorimetry and proton nuclear magnetic resonance spectroscopy. In vitro, human CNE-2Z and MDA-MB-231 tumor cells were used to evaluate 3BP-LCNP-FA effects on tumor cell morphology and proliferation. Different drug formulations were administered to tumor-bearing nude mice to observe the treatment effects. Hepatic and renal toxicities were assessed using hematoxylin and eosin-stained liver, kidney, and lung sections along with serological analysis of liver and kidney injury markers (e.g., aspartate aminotransferase, alanine transaminase, blood urea nitrogen, and creatinine). Tumor tissue was observed for changes using proliferating cell nuclear antigen immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling assay.

RESULTS: We successfully prepared 3BP-LCNP-FA of spherical shape with uniform size using the aforementioned techniques; drug loading did not alter crystal morphology. These cubosomes exhibited more potent antitumor activity than 3-bromopyruvate alone or non-folic acid-conjugated 3-bromopyruvate liquid crystalline nanoparticles in vitro and in vivo without obvious toxic side effects.

CONCLUSIONS: It is possible to successfully construct 3BP-LCNP-FA as a drug delivery vehicle that is more efficacious than 3-bromopyruvate and has no obvious toxic effects. Thus, folic acid-modified cubosomes can be used as effective carriers for targeted drug administration.

Keywords: Drug Delivery Systems, Folic Acid, Nanoparticles

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750