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
AbstractMinimization 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.
|Journal series||Biomacromolecules, ISSN 1525-7797, e-ISSN 1526-4602, (N/A 140 pkt)|
|Publication size in sheets||0.8|
|ASJC Classification||; ; ;|
|Publication indicators||= 0; : 2018 = 1.256; : 2018 = 5.667 (2) - 2018=5.826 (5)|
|Finansowanie||This 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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