Novel Fluorescent Benzimidazole-Hydrazone-Loaded Micellar Carriers for Controlled Release - Impact on Cell Toxicity, Nuclear and Microtubule Alterations in Breast Cancer Cells

Sep 24, 2026

Uploaded by Jake

Fluorescent micellar carriers with controlled release of a novel anticancer drug were developed to support simultaneous intracellular imaging and cancer treatment. The nanosized fluorescent systems embedded a benzimidazole-hydrazone (BzH) drug through self-assembly of PAA-b-PnBA block copolymers prepared by ATRP. Blank and drug-loaded micelles were characterized by DLS, TEM, and fluorescence spectroscopy. After 72 h, released drug amount reached 3.25 µM, showing enhanced antiproliferative and cytotoxic effects on MDA-MB-231 cells, long-lasting microtubule organization disruption, apoptotic alterations, and perinuclear localization, while effects on MCF-10A were weaker.

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1. Introduction

pharmaceutics Article Novel Fluorescent Benzimidazole-Hydrazone-Loaded Micellar Carriers for Controlled Release: Impact on Cell Toxicity, Nuclear and Microtubule Alterations in Breast Cancer Cells Rayna Bryaskova 1, *, Nikolai Georgiev 2, Nikoleta Philipova 1, Ventsislav Bakov 2, Kameliya Anichina 2, Maria Argirova 3, Sonia Apostolova 4, Irina Georgieva 4 and Rumiana Tzoneva 4 Citation: Bryaskova, R.; Georgiev, N.; Philipova, N.; Bakov, V.; Anichina, K.; Argirova, M.; Apostolova, S.; Georgieva, I.; Tzoneva, R. Novel Fluorescent BenzimidazoleHydrazone-Loaded Micellar Carriers for Controlled Release: Impact on Cell Toxicity, Nuclear and Microtubule Alterations in Breast Cancer Cells. Pharmaceutics 2023, 15, 1753. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)pharmaceutics15061753 Academic Editors: Stanislav Rangelov and Emi Haladjova Received: 29 May 2023 Revised: 11 June 2023 Accepted: 14 June 2023 Published: 16 June 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Polymer Engineering, University of Chemical Technology and Metallurgy, 8 Kliment Ohridsky Str., 1756 Soﬁa, Bulgaria 2 Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridsky Str., 1756 Soﬁa, Bulgaria 3 Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Soﬁa, Bulgaria 4 Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Science, Acad. G. Bonchev Str., Bl. 21, 1113 Soﬁa, Bulgaria * Correspondence: [rbryaskova@uctm.edu](rbryaskova@uctm.edu) Abstract: Fluorescent micellar carriers with controlled release of a novel anticancer drug were developed to enable intracellular imaging and cancer treatment simultaneously. The nanosized ﬂuorescent micellar systems were embedded with a novel anticancer drug via the self-assembling behavior of well-deﬁned block copolymers based on amphiphilic poly(acrylic acid)-block-poly(nbutyl acrylate) (PAA-b-PnBA) copolymer obtained by Atom Transfer Radical Polymerization (ATRP) and hydrophobic anticancer benzimidazole-hydrazone drug (BzH) . Through this method, welldeﬁned nanosized ﬂuorescent micelles were obtained consisting of a hydrophilic PAA shell and a hydrophobic PnBA core embedded with the BzH drug due to the hydrophobic interactions, thus reaching very high encapsulation efﬁciency. The size, morphology, and ﬂuorescent properties of blank and drug-loaded micelles were investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM), and ﬂuorescent spectroscopy, respectively. Additionally, after 72 hof incubation, drug-loaded micelles released 3.25 􀀖M of BzH, which was spectrophotometrically determined. The BzH drug-loaded micelles were found to exhibit enhanced antiproliferative and cytotoxic effects on MDA-MB-231 cells, with long-lasting effects on microtubule organization, with apoptotic alterations and preferential localization in the perinuclear space of cancer cells. In contrast, the antitumor effect of BzH alone or incorporated in micelles on non-cancerous cells MCF-10A was relatively weak. Keywords: drug carriers; micelles; ﬂuorescence; benzimidazole derivatives; drug release; cytotoxicity; nuclear and microtubule alterations 1. Introduction Cancer is a leading cause of mortality worldwide, responsible for estimated 10 million deaths in 2020, according to the World Health Organization (WHO) [1] . Fundamental discoveries and new technologies in the last decade have led to major advances in understanding the mechanisms of this heterogeneous disease. The traditional chemical drugs for cancer trea

FAQs

How were the fluorescent micellar carriers designed for controlled drug release?

They were built as nanosized fluorescent micelles formed by self-assembling PAA-b-PnBA block copolymers (from ATRP) that embed the hydrophobic benzimidazole-hydrazone drug (BzH) via hydrophobic interactions.

What methods were used to study the micelles and their drug release?

Blank and drug-loaded micelles were investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM), and fluorescence spectroscopy, and drug release was determined spectrophotometrically after incubation.

What biological effects did BzH-loaded micelles show in breast cancer cells compared with the free drug?

BzH-loaded micelles enhanced antiproliferative and cytotoxic effects on MDA-MB-231 cells, produced long-lasting microtubule organization disruption with apoptotic alterations, and localized preferentially in the perinuclear space, whereas BzH alone (and micelle-incorporated BzH) showed relatively weak effects on non-cancerous MCF-10A cells.

Sep 24, 2026

Uploaded by Jake