Encapsulation of Doxorubicin in Furcellaran/Chitosan Nanocapsules by Layer-by-Layer Technique for Selectively Controlled Drug Delivery

Vedran Milosavljević , Ewelina Jamróz , Milica Gagic , Yazan Haddad , Hana Michalkova , Radka Balková , Barbora Tesarova , Amitava Moulick , Zbynek Heger , Lukas Richtera , Pavel Kopel , Vojtech Adam

Abstract

Minimization of drug side effects is a hallmark of advanced targeted therapy. Herein we describe the synthesis of polysaccharide-based nanocapsules prepared from furcellaran and chitosan via layer-by-layer deposition using electrostatic interaction. Using doxorubicin as a model drug, prepared nanocapsules showed excellent drug loading properties and release influence by pH and stability. Targeted delivery of doxorubicin was achieved by nanocapsule surface modification using homing peptide (seq SMSIARLC). The synthesized nanocapsules possess excellent compatibility to eukaryotic organisms. In the case of nonmalignant cells (PNT1A and HEK-293), toxicity tests revealed the absences of DNA fragmentation, apoptosis, necrosis, and also disruption of erythrocyte membranes. In contrast, results from treatment of malignant cell lines (MDA-MB-231 and PC3) indicate good anticancer effects of synthesized bionanomaterial. Internalization studies revealed the nanocapsule’s ability to enter the malignant cell lines by endocytosis and triggering the apoptosis. The occurrence of apoptosis is mostly connected to the presence of ROS and inability of DNA damage reparation. Additionally, the obtained results strongly indicate that peptide modification increases the speed of nanocapsule internalization into malignant cell lines while simultaneously nonmalignant cell lines are untouched by nanocapsules highlighting the strong selectivity of the peptide.
Author Vedran Milosavljević - Brno University of Technology
Vedran Milosavljević,,
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, Ewelina Jamróz (FoFT / DoCh)
Ewelina Jamróz,,
- Department of Chemistry
, Milica Gagic - Brno University of Technology
Milica Gagic,,
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, Yazan Haddad - Brno University of Technology
Yazan Haddad,,
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, Hana Michalkova - Brno University of Technology
Hana Michalkova,,
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, Radka Balková - Mendel University in Brno
Radka Balková,,
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, Barbora Tesarova - Brno University of Technology
Barbora Tesarova,,
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, Amitava Moulick - Brno University of Technology
Amitava Moulick,,
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, Zbynek Heger - Brno University of Technology
Zbynek Heger,,
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, Lukas Richtera - Brno University of Technology
Lukas Richtera,,
-
et al.`
Journal seriesBiomacromolecules, ISSN 1525-7797, e-ISSN 1526-4602, (N/A 140 pkt)
Issue year2020
Vol21
No2
Pages418-434
Publication size in sheets0.8
ASJC Classification1502 Bioengineering; 2502 Biomaterials; 2505 Materials Chemistry; 2507 Polymers and Plastics
DOIDOI:10.1021/acs.biomac.9b01175
URL https://pubs.acs.org/doi/10.1021/acs.biomac.9b01175
Languageen angielski
Score (nominal)140
Score sourcejournalList
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.256; WoS Impact Factor: 2018 = 5.667 (2) - 2018=5.826 (5)
Citation count*
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FinansowanieThis research was carried out under the project CEITEC 2020 (LQ1601) with financial support from the Ministry of Education, Youth and Sports of the Czech Republic under the National Sustainability Programme II, and by ERDF “Multidisciplinary research to increase application potential of nanomaterials in agricultural” (No. CZ.02.1.01/0.0/0.0/16_025/0007314). Brno PhD. Talent Scholarship Holder – Funded by the Brno City Municipality
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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