PMID- 34278745
OWN - NLM
STAT- MEDLINE
DCOM- 20220210
LR  - 20231107
IS  - 2198-3844 (Electronic)
IS  - 2198-3844 (Linking)
VI  - 8
IP  - 18
DP  - 2021 Sep
TI  - Biodegradable and Dual-Responsive Polypeptide-Shelled Cyclodextrin-Containers for 
      Intracellular Delivery of Membrane-Impermeable Cargo.
PG  - e2100694
LID - 10.1002/advs.202100694 [doi]
LID - 2100694
AB  - The transport of membrane impermeable compounds into cells is a prerequisite for 
      the efficient cellular delivery of hydrophilic and amphiphilic compounds and 
      drugs. Transport into the cell's cytosolic compartment should ideally be 
      controllable and it should involve biologically compatible and degradable 
      vehicles. Addressing these challenges, nanocontainers based on cyclodextrin 
      amphiphiles that are stabilized by a biodegradable peptide shell are developed 
      and their potential to deliver fluorescently labeled cargo into human cells is 
      analyzed. Host-guest mediated self-assembly of a thiol-containing short peptide 
      or a cystamine-cross-linked polypeptide shell on cyclodextrin vesicles produce 
      short peptide-shelled (SPSV(ss) ) or polypeptide-shelled vesicles (PPSV(ss) ), 
      respectively, with redox-responsive and biodegradable features. Whereas SPSV(ss) 
      are permeable and less stable, PPSV(ss) effectively encapsulate cargo and show a 
      strictly regulated release of membrane impermeable cargo triggered by either 
      reducing conditions or peptidase treatment. Live cell experiments reveal that the 
      novel PPSV(SS) are readily internalized by primary human endothelial cells (human 
      umbilical vein endothelial cells) and cervical cancer cells and that the 
      reductive microenvironment of the cells' endosomes trigger release of the 
      hydrophilic cargo into the cytosol. Thus, PPSV(SS) represent a highly efficient, 
      biodegradable, and tunable system for overcoming the plasma membrane as a natural 
      barrier for membrane-impermeable cargo.
CI  - (c) 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.
FAU - Kudruk, Sergej
AU  - Kudruk S
AD  - Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, 
      University of Muenster, Von-Esmarch-Str. 56, Munster, 48149, Germany.
FAU - Pottanam Chali, Sharafudheen
AU  - Pottanam Chali S
AD  - Center for Soft Nanoscience and Organic Chemistry Institute, University of 
      Muenster, Busso Peus Strasse 10, Munster, 48149, Germany.
FAU - Linard Matos, Anna Livia
AU  - Linard Matos AL
AD  - Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, 
      University of Muenster, Von-Esmarch-Str. 56, Munster, 48149, Germany.
FAU - Bourque, Cole
AU  - Bourque C
AD  - Center for Soft Nanoscience and Institute of Medical Physics and Biophysics, 
      University of Muenster, Busso Peus Strasse 10, Munster, 48149, Germany.
AD  - Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, Dortmund, 
      44227, Germany.
FAU - Dunker, Clara
AU  - Dunker C
AD  - Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, 
      University of Muenster, Von-Esmarch-Str. 56, Munster, 48149, Germany.
FAU - Gatsogiannis, Christos
AU  - Gatsogiannis C
AD  - Center for Soft Nanoscience and Institute of Medical Physics and Biophysics, 
      University of Muenster, Busso Peus Strasse 10, Munster, 48149, Germany.
AD  - Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, Dortmund, 
      44227, Germany.
FAU - Ravoo, Bart Jan
AU  - Ravoo BJ
AUID- ORCID: 0000-0003-2202-7485
AD  - Center for Soft Nanoscience and Organic Chemistry Institute, University of 
      Muenster, Busso Peus Strasse 10, Munster, 48149, Germany.
FAU - Gerke, Volker
AU  - Gerke V
AUID- ORCID: 0000-0001-7208-8206
AD  - Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, 
      University of Muenster, Von-Esmarch-Str. 56, Munster, 48149, Germany.
LA  - eng
GR  - SFB 858/B19/Deutsche Forschungsgemeinschaft/
GR  - GE514/6-3/Deutsche Forschungsgemeinschaft/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210718
PL  - Germany
TA  - Adv Sci (Weinh)
JT  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
JID - 101664569
RN  - 0 (Cyclodextrins)
RN  - 0 (Peptides)
SB  - IM
MH  - Cyclodextrins/*metabolism
MH  - Drug Delivery Systems/*methods
MH  - *Drug Liberation
MH  - Endothelial Cells/*metabolism
MH  - Humans
MH  - *Hydrophobic and Hydrophilic Interactions
MH  - Nanoparticles/metabolism
MH  - Peptides/*metabolism
PMC - PMC8456233
OTO - NOTNLM
OT  - biodegradable
OT  - cyclodextrin
OT  - dual-responsive
OT  - intracellular delivery
OT  - polypeptides
COIS- The authors declare no conflict of interest.
EDAT- 2021/07/20 06:00
MHDA- 2022/02/11 06:00
PMCR- 2021/07/18
CRDT- 2021/07/19 06:31
PHST- 2021/07/01 00:00 [revised]
PHST- 2021/02/19 00:00 [received]
PHST- 2021/07/20 06:00 [pubmed]
PHST- 2022/02/11 06:00 [medline]
PHST- 2021/07/19 06:31 [entrez]
PHST- 2021/07/18 00:00 [pmc-release]
AID - ADVS2902 [pii]
AID - 10.1002/advs.202100694 [doi]
PST - ppublish
SO  - Adv Sci (Weinh). 2021 Sep;8(18):e2100694. doi: 10.1002/advs.202100694. Epub 2021 
      Jul 18.