Synthesis of nanostructured polypeptide materials based on poly(cysteine) and poly(histidine) for the encapsulation and release of anticancer drugs

Doctoral Dissertation uoadl:2946167 131 Read counter

Unit:
Department of Chemistry
Library of the School of Science
Deposit date:
2021-05-26
Year:
2021
Author:
Stavroulaki Dimitra
Dissertation committee:
Ιατρού Ερμόλαος, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Πιτσικάλης Μαρίνος, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Παπαευσταθίου Ιωάννης, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Σακελλαρίου Γεώργιος, Αναπληρωτής Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Χατζηχρηστίδη Μαργαρίτα, Αναπληρώτρια Καθηγήτρια, Τμήμα Χημείας, ΕΚΠΑ
Δήμας Κωνσταντίνος, Αναπληρωτής Καθηγητής, Τμήμα Ιατρικής, Παν. Θεσσαλίας
Φραγκούλη Παναγιώτα, Επίκουρος Καθηγήτρια, Τμήμα Μηχανικών Βιομηχανικής Σχεδίασης και Παραγωγής, ΠΑΔΑ
Original Title:
Σύνθεση νανοδομημένων πολυπεπτιδικών υλικών βασισμένα στην πολυ(κυστεΐνη) και την πολυ(ιστιδίνη) για τον εγκλωβισμό και αποδέσμευση αντικαρκινικών φαρμάκων
Languages:
Greek
Translated title:
Synthesis of nanostructured polypeptide materials based on poly(cysteine) and poly(histidine) for the encapsulation and release of anticancer drugs
Summary:
In the present research project, the synthesis of a series of hybrid polypeptide copolymers based on poly(histidine) and poly(cysteine), of the general type PEO-b-P(Cys)-b-P(His) is presented. The synthesis of polymers was achieved through ring-opening polymerization (ROP) process of the corresponding protected N-carboxy anhydrides (monomers), using an amine end-functionalized poly(ethylene oxide) (mPEO-NH2) macroinitiator. High-vacuum techniques were used for the synthesis of N-carboxy anhydrides of α-amino acids, for the purification of solvents and for the isolation of well-defined polymers as well, ensuring the high purity of the system. The successful synthesis of the polymers was confirmed by Size Exclusion Chromatography (SEC), proton Nuclear Magnetic Resonance (1H-NMR) and Fourier-Transform Infrared Spectroscopy (FT-IR). In addition, the relation between the secondary structure of the polypeptides, and the pH and the temperature was studied, using the technique of circular dichroism (CD). Dynamic Light Scattering (DLS), Static Light Scattering (SLS) and Transmission Electron Microscopy were employed, in order to investigate the ability of the polypeptides to self-assemble into micelles, as well as their size. Z-potential measurements revealed the surface charge of the synthesized nanoparticles. These amphiphilic copolymers of the PEO-b-P(Cys)-b-P(His) type possess the ability to self-assemble in aqueous media and form micelle-like nanostructures, comprised of an outer hydrophilic corona of poly(ethylene oxide) chains, and a pH- and a redox- responsive hydrophobic core based on poly(histidine) and poly(cysteine). These nanoparticles have the ability to encapsulate and release the anticancer drug of doxorubicin in a controlled manner at cancer tissue conditions, as in vitro trials in breast cancer cell lines revealed.
Main subject category:
Science
Keywords:
polypeptides, secondary structure, nanoparticles, doxorubicin, breast cancer
Index:
Yes
Number of index pages:
7
Contains images:
Yes
Number of references:
137
Number of pages:
242
File:
File access is restricted until 2024-05-27.

STAVROULAKI DIMITRA_DIDAKTORIKO.pdf
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File access is restricted until 2024-05-27.