PMID- 33073549
OWN - NLM
STAT- MEDLINE
DCOM- 20211011
LR  - 20231111
IS  - 2366-7478 (Print)
IS  - 2366-7478 (Electronic)
IS  - 2366-7478 (Linking)
VI  - 4
IP  - 11
DP  - 2020 Nov
TI  - Ligand Density Controls C-Type Lectin-Like Molecule-1 Receptor-Specific Uptake of 
      Polymer Nanoparticles.
PG  - e2000172
LID - 10.1002/adbi.202000172 [doi]
AB  - The newest generation of drug delivery systems (DDSs) exploits ligands to mediate 
      specific targeting of cells and/or tissues. However, studies investigating the 
      link between ligand density and nanoparticle (NP) uptake are limited to a small 
      number of ligand-receptor systems. C-type lectin-like molecule-1 (CLL1) is 
      uniquely expressed on myeloid cells, which enables the development of receptors 
      specifically targeting treat various diseases. This study aims to investigate how 
      NPs with different CLL1 targeting peptide density impact cellular uptake. To this 
      end, poly(styrene-alt-maleic anhydride)-b-poly(styrene) NPs are functionalized 
      with cyclized CLL1 binding peptides (cCBP) ranging from 240 +/- 12 to 31 000 +/- 940 
      peptides per NP. Unexpectedly, the percentage of cells with internalized NPs is 
      decreased for all cCBP-NP designs regardless of ligand density compared to 
      unmodified NPs. Internalization through CLL1 receptor-mediated processes is 
      further investigated without confounding the effects of NP size and surface 
      charge. Interestingly, high density cCBP-NPs (>7000 cCBP per NP) uptake is 
      dominated by CLL1 receptor-mediated processes while low density cCBP-NPs ( approximately 200 
      cCBP per NP) and untargeted NP occurred through non-specific clathrin and 
      caveolin-mediated endocytosis. Altogether, these studies show that ligand density 
      and uptake mechanism should be carefully investigated for specific 
      ligand-receptor systems for the design of targeted DDSs to achieve effective drug 
      delivery.
CI  - (c) 2020 Wiley-VCH GmbH.
FAU - Ackun-Farmmer, Marian A
AU  - Ackun-Farmmer MA
AUID- ORCID: 0000-0003-3081-5115
AD  - University of Rochester, Department of Biomedical Engineering, Rochester, NY, 
      USA.
AD  - University of Rochester Medical Center, Department of Orthopaedics and Center for 
      Musculoskeletal Research, Rochester, NY, USA.
FAU - Alatise, Kharimat L
AU  - Alatise KL
AD  - University of Rochester, Department of Biomedical Engineering, Rochester, NY, 
      USA.
FAU - Cross, Griffin
AU  - Cross G
AD  - Washington University in St. Louis, Biomedical/Medical Engineering, St. Louis, 
      MO, USA.
FAU - Benoit, Danielle S W
AU  - Benoit DSW
AUID- ORCID: 0000-0001-7137-8164
AD  - University of Rochester, Department of Biomedical Engineering, Rochester, NY, 
      USA.
AD  - University of Rochester Medical Center, Department of Orthopaedics and Center for 
      Musculoskeletal Research, Rochester, NY, USA.
AD  - University of Rochester, Materials Science Program, Rochester, NY, USA.
AD  - University of Rochester, Department of Chemical Engineering, Rochester, NY, USA.
LA  - eng
GR  - P30 AR069655/AR/NIAMS NIH HHS/United States
GR  - UL1 TR002001/TR/NCATS NIH HHS/United States
GR  - R01 AR056696/AR/NIAMS NIH HHS/United States
GR  - R01 AR064200/AR/NIAMS NIH HHS/United States
GR  - F31 CA228391/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20201019
PL  - Germany
TA  - Adv Biosyst
JT  - Advanced biosystems
JID - 101711718
RN  - 0 (Cell Adhesion Molecule-1)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Ligands)
RN  - 0 (Peptides)
RN  - 0 (Polymers)
SB  - IM
MH  - Cell Adhesion Molecule-1/chemistry/metabolism
MH  - Cell Line, Tumor
MH  - Drug Delivery Systems/*methods
MH  - Humans
MH  - *Lectins, C-Type/chemistry/metabolism
MH  - Ligands
MH  - *Nanoparticles/chemistry/metabolism
MH  - Peptides/chemistry/metabolism
MH  - Polymers/chemistry/pharmacokinetics
PMC - PMC7959326
MID - NIHMS1672499
OTO - NOTNLM
OT  - C-type lectin-like molecule-1 binding peptides
OT  - cell uptake
OT  - ligand density
COIS- Conflict of Interest The authors declare no conflict of interest.
EDAT- 2020/10/20 06:00
MHDA- 2021/10/12 06:00
PMCR- 2021/03/15
CRDT- 2020/10/19 06:05
PHST- 2020/07/01 00:00 [received]
PHST- 2020/10/01 00:00 [revised]
PHST- 2020/10/20 06:00 [pubmed]
PHST- 2021/10/12 06:00 [medline]
PHST- 2020/10/19 06:05 [entrez]
PHST- 2021/03/15 00:00 [pmc-release]
AID - 10.1002/adbi.202000172 [doi]
PST - ppublish
SO  - Adv Biosyst. 2020 Nov;4(11):e2000172. doi: 10.1002/adbi.202000172. Epub 2020 Oct 
      19.