PMID- 31292126
OWN - NLM
STAT- MEDLINE
DCOM- 20200707
LR  - 20200707
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 3
IP  - 14
DP  - 2019 Jul 23
TI  - Dual-action CXCR4-targeting liposomes in leukemia: function blocking and drug 
      delivery.
PG  - 2069-2081
LID - 10.1182/bloodadvances.2019000098 [doi]
AB  - CXC chemokine receptor 4 (CXCR4) is overexpressed by a broad range of 
      hematological disorders, and its interaction with CXC chemokine ligand 12 
      (CXCL12) is of central importance in the retention and chemoprotection of 
      neoplastic cells in the bone marrow and lymphoid organs. In this article, we 
      describe the biological evaluation of a new CXCR4-targeting and -antagonizing 
      molecule (BAT1) that we designed and show that, when incorporated into a 
      liposomal drug delivery system, it can be used to deliver cancer therapeutics at 
      high levels to chronic lymphocytic leukemia (CLL) cells. CXCR4 targeting and 
      antagonism by BAT1 were demonstrated alone and following its incorporation into 
      liposomes (BAT1-liposomes). Antagonism of BAT1 against the CXCR4/CXCL12 
      interaction was demonstrated through signaling inhibition and function blocking: 
      BAT1 reduced ERK phosphorylation and cell migration to levels equivalent to those 
      seen in the absence of CXCL12 stimulation (P < .001). Specific uptake of 
      BAT1-liposomes and delivery of a therapeutic cargo to the cell nucleus was seen 
      within 3 hours of incubation and induced significantly more CLL cell death after 
      24 hours than control liposomes (P = .004). The BAT1 drug-delivery system is 
      modular, versatile, and highly clinically relevant, incorporating elements of 
      proven clinical efficacy. The combined capabilities to block CXCL12-induced 
      migration and intracellular signaling while simultaneously delivering therapeutic 
      cargo mean that the BAT1-liposome drug-delivery system could be a timely and 
      relevant treatment of a range of hematological disorders, particularly because 
      the therapeutic cargo can be tailored to the disease being treated.
CI  - (c) 2019 by The American Society of Hematology.
FAU - McCallion, Catriona
AU  - McCallion C
AD  - School of Chemistry.
AD  - Manchester Institute of Biotechnology, and.
AD  - Division of Cancer Sciences, School of Medical Sciences, University of 
      Manchester, Manchester, United Kingdom.
FAU - Peters, Anna D
AU  - Peters AD
AD  - School of Chemistry.
AD  - Manchester Institute of Biotechnology, and.
FAU - Booth, Andrew
AU  - Booth A
AD  - School of Chemistry.
AD  - Manchester Institute of Biotechnology, and.
FAU - Rees-Unwin, Karen
AU  - Rees-Unwin K
AD  - Division of Cancer Sciences, School of Medical Sciences, University of 
      Manchester, Manchester, United Kingdom.
FAU - Adams, Julie
AU  - Adams J
AD  - Department of Haematology, Manchester Royal Infirmary, Manchester University NHS 
      Foundation Trust, Manchester, United Kingdom.
FAU - Rahi, Raisa
AU  - Rahi R
AD  - Division of Cancer Sciences, School of Medical Sciences, University of 
      Manchester, Manchester, United Kingdom.
FAU - Pluen, Alain
AU  - Pluen A
AD  - Division of Pharmacy and Optometry, School of Health Sciences, University of 
      Manchester, Manchester, United Kingdom.
FAU - Hutchinson, Claire V
AU  - Hutchinson CV
AD  - Faculty of Dentistry and Medicine, Peninsula Medical School, University of 
      Plymouth, Plymouth, United Kingdom; and.
AD  - University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom.
FAU - Webb, Simon J
AU  - Webb SJ
AUID- ORCID: 0000-0001-9793-8748
AD  - School of Chemistry.
AD  - Manchester Institute of Biotechnology, and.
FAU - Burthem, John
AU  - Burthem J
AD  - Division of Cancer Sciences, School of Medical Sciences, University of 
      Manchester, Manchester, United Kingdom.
AD  - Department of Haematology, Manchester Royal Infirmary, Manchester University NHS 
      Foundation Trust, Manchester, United Kingdom.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Drug Carriers)
RN  - 0 (Liposomes)
RN  - 0 (Receptors, CXCR4)
RN  - 80168379AG (Doxorubicin)
RN  - EC 3.6.1.- (DDX39B protein, human)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
MH  - Antineoplastic Agents/*administration & dosage/chemistry
MH  - Cell Survival
MH  - Chemokine CXCL12/antagonists & inhibitors
MH  - DEAD-box RNA Helicases/chemistry/*metabolism
MH  - Doxorubicin/administration & dosage/chemistry
MH  - *Drug Carriers/chemistry
MH  - *Drug Delivery Systems
MH  - Humans
MH  - Leukemia/drug therapy/genetics/metabolism/pathology
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/metabolism/pathology
MH  - *Liposomes/chemistry
MH  - Lymphocytes/immunology/metabolism
MH  - Molecular Structure
MH  - Molecular Targeted Therapy
MH  - Protein Binding
MH  - Receptors, CXCR4/antagonists & inhibitors/chemistry/*metabolism
PMC - PMC6650733
COIS- Conflict-of-interest disclosure: The authors declare no competing financial 
      interests.
EDAT- 2019/07/12 06:00
MHDA- 2020/07/08 06:00
PMCR- 2019/07/10
CRDT- 2019/07/12 06:00
PHST- 2019/03/04 00:00 [received]
PHST- 2019/05/24 00:00 [accepted]
PHST- 2019/07/12 06:00 [entrez]
PHST- 2019/07/12 06:00 [pubmed]
PHST- 2020/07/08 06:00 [medline]
PHST- 2019/07/10 00:00 [pmc-release]
AID - bloodadvances.2019000098 [pii]
AID - 2019/ADV2019000098 [pii]
AID - 10.1182/bloodadvances.2019000098 [doi]
PST - ppublish
SO  - Blood Adv. 2019 Jul 23;3(14):2069-2081. doi: 10.1182/bloodadvances.2019000098.