Engineering of doxorubicin-encapsulating and TRAIL-conjugated poly(RGD) proteinoid nanocapsules for drug delivery applications

Elad Hadad, Safra Rudnick-Glick, Ella Itzhaki, Matan Y. Avivi, Igor Grinberg, Yuval Elias, Shlomo Margel

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Proteinoids are non-toxic biodegradable polymers prepared by thermal step-growth polymerization of amino acids. Here, P(RGD) proteinoids and proteinoid nanocapsules (NCs) based on D-arginine, glycine, and L-aspartic acid were synthesized and characterized for targeted tumor therapy. Doxorubicin (Dox), a chemotherapeutic drug used for treatment of a wide range of cancers, known for its adverse side effects, was encapsulated during self-assembly to form Dox/P(RGD) NCs. In addition, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which can initiate apoptosis in most tumor cells but undergoes fast enzyme degradation, was stabilized by covalent conjugation to hollow P(RGD) NCs. The effect of polyethylene glycol (PEG) conjugation was also studied. Cytotoxicity tests on CAOV-3 ovarian cancer cells demonstrated that Dox/P(RGD) and TRAIL-P(RGD) NCs were as effective as free Dox and TRAIL with cell viability of 2% and 10%, respectively, while PEGylated NCs were less effective. Drug-bearing P(RGD) NCs offer controlled release with reduced side effects for improved therapy.

Original languageEnglish
Article number2996
Pages (from-to)1-14
Number of pages14
JournalPolymers
Volume12
Issue number12
DOIs
StatePublished - 16 Dec 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Doxorubicin
  • Proteinoid
  • RGD
  • TRAIL

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