Modulation of hydrogel nanoparticle intracellular trafficking by multivalent surface engineering with tumor targeting peptide.
Surface engineering of a hydrogel nanoparticle (NP) with the tumor-targeting ligand, F3 peptide, enhances both the NP's binding affinity for, and internalization by, nucleolin overexpressing tumor cells. Remarkably, the F3-functionalized NPs consistently exhibited significantly lower trafficking to the degradative lysosomes than the non-functionalized NPs, in the tumor cells, after internalization. This is attributed to the non-functionalized NPs, but not the F3-functionalized NPs, being co-internalized with Lysosome-associated Membrane Protein-1 (LAMP1) from the surface of the tumor cells. Furthermore, it is shown that the intracellular trafficking of the F3-functionalized NPs differs significantly from that of the molecular F3 peptides (untethered to NPs). This has important implications for designing effective, chemically-responsive, controlled-release and multifunctional nanodrugs for multi-drug-resistant cancers.
Department of Chemistry, University of Michigan, 930 North University Ave, Ann Arbor, Michigan 48109, USA. kopelman@umich.edu.
Leshern
L
Karamchand
Gwangseong
G
Kim
Shouyan
S
Wang
Hoe Jin
HJ
Hah
Aniruddha
A
Ray
Ruba
R
Jiddou
Yong-Eun
YE
Koo Lee
Martin A
MA
Philbert
Raoul
R
Kopelman
D000180:Acrylic Resins / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002746:Chlorpromazine / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000737:chemistry / Q000378:metabolism; D008247:Lysosomes / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D013499:Surface Properties; D000097796:Nucleolin; D000099166:Polyacrylamides
D000180:Acrylic Resins; D016588:Anticarcinogenic Agents; D002746:Chlorpromazine; D015638:Cytochalasin D; D019833:Genistein; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D052118:Lysosomal-Associated Membrane Protein 1; D010455:Peptides; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; D000099166:Polyacrylamides