A comparison of acyl-moieties for noncovalent functionalization of PLGA and PEG-PLGA nanoparticles with a cell-penetrating peptide

• Published in: RSC advances Vol. 11; no. 57; pp. 36116 - 36124
• Main Authors: Paulino da Silva Filho, Omar, Ali, Muhanad, Nabbefeld, Rike, Primavessy, Daniel, Bovee-Geurts, Petra H, Grimm, Silko, Kirchner, Andreas, Wiesmüller, Karl-Heinz, Schneider, Marc, Walboomers, X. Frank, Brock, Roland
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 10.11.2021; The Royal Society of Chemistry
• Subjects: Acylation; Block copolymers; Chemistry; Conjugation; drugs; endocytosis; nanomedicine; Nanoparticles; particle size; Peptides; polymers; storage quality; Storage stability
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d1ra05871a

Efficient intracellular drug delivery in nanomedicine strongly depends on ways to induce cellular uptake. Conjugation of nanoparticles (NPs) with cell-penetrating peptides (CPPs) is a known means to induce uptake via endocytosis. Here, we functionalized NPs consisting of either poly( d , l -lactide- co -glycolide) (PLGA) or polyethene glycol (PEG)-PLGA block-copolymer with a lactoferrin-derived cell-penetrating peptide (hLF). To enhance the association between the peptide and the polymer NPs, we tested a range of acyl moieties for N-terminal acylation of the peptide as a means to promote noncovalent interactions. Acyl moieties differed in chain length and number of acyl chains. Peptide-functionalized NPs were characterized for nanoparticle size, overall net charge, storage stability, and intracellular uptake. Coating particles with a palmitoylated hLF resulted in minimal precipitation after storage at −20C and homogeneous particle size (<200 nm). Palmitoyl-hLF coated NPs showed enhanced delivery in different cells in comparison to NPs lacking functionalization. Moreover, in comparison to acetyl-hLF, palmitoyl-hLF was also suited for coating and enhancing the cellular uptake of PEG-PLGA NPs. Noncovalent functionalization with acylated cell-penetrating peptides achieves an efficient cellular uptake of PLGA and PEG-PLGA nanoparticles.