TY - JOUR
T1 - Immunomodulation of hematological malignancies using oligonucleotides based-nanomedicines
AU - Hazan-Halevy, Inbal
AU - Landesman-Milo, Dalit
AU - Rosenblum, Daniel
AU - Mizrahy, Shoshy
AU - Ng, Brandon D.
AU - Peer, Dan
N1 - Funding Information:
B.D.N acknowledges the Fulbright Fellowship . This work was supported in part by grants from the NIH ( 5R01CA139444-10 ); The Dotan Hematology Center at Tel Aviv University ; The Lewis Family Trust ; The William Cohen Trust for CLL ; the I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (Grant 41/11 ); the FTA: Nanomedicines for Personalized Theranostics of the Israeli National Nanotechnology Initiative ; by The Leona M. and Harry B. Helmsley Nanotechnology Research Fund and By the ERC grant LeukoTheranostics (# 647410 ) awarded to D.P.
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/12/28
Y1 - 2016/12/28
N2 - Hematological malignancies are a group of diseases characterized by clonal proliferation of blood-forming cells. Malignant blood cells are classified as myeloid or lymphoid cells depending on their stem cell origin. Lymphoid malignancies are characterized by lymphocyte accumulation in the blood stream, in the bone marrow, or in lymphatic nodes and organs. Several of these diseases are associated with chromosomal translocations, which cause gene fusion and amplification of expression, while others are characterized with aberrant expression of oncogenes. Overall, these genes play a major role in development and maintenance of malignant clones. The discovery of antisense oligonucleotides and RNA interference (RNAi) mechanisms offer new tools to specifically manipulate gene expression. Systemic delivery of inhibitory oligonucleotides molecules for manipulation of gene expression in lymphocytes holds a great potential for facilitating the development of an oligonucleotides -based therapy platform for lymphoid blood cancer. However, lymphocytes are among the most difficult targets for oligonucleotides delivery, as they are resistant to conventional transfection reagents and are dispersed throughout the body, making it difficult to successfully localize or deliver oligonucleotides payloads via systemic administration. In this review, we will survey the latest progress in the field of oligonucleotides based nanomedicine in the heterogeneous group of hematological malignancies with special emphasis on RNA based strategies. We will describe the most advanced non-viral nanocarriers for RNA delivery to malignant blood cells. We will also discuss targeted strategies for cell specific delivery of RNA molecules using nanoparticles and the therapeutic benefit of manipulating gene function in hematological malignancies. Finally, we will focus on the ex vivo, in vivo, and clinical trial strategies, that are currently under development in hematological malignancies - strategies that might increase the arsenal of drugs available to hematologists in the upcoming years.
AB - Hematological malignancies are a group of diseases characterized by clonal proliferation of blood-forming cells. Malignant blood cells are classified as myeloid or lymphoid cells depending on their stem cell origin. Lymphoid malignancies are characterized by lymphocyte accumulation in the blood stream, in the bone marrow, or in lymphatic nodes and organs. Several of these diseases are associated with chromosomal translocations, which cause gene fusion and amplification of expression, while others are characterized with aberrant expression of oncogenes. Overall, these genes play a major role in development and maintenance of malignant clones. The discovery of antisense oligonucleotides and RNA interference (RNAi) mechanisms offer new tools to specifically manipulate gene expression. Systemic delivery of inhibitory oligonucleotides molecules for manipulation of gene expression in lymphocytes holds a great potential for facilitating the development of an oligonucleotides -based therapy platform for lymphoid blood cancer. However, lymphocytes are among the most difficult targets for oligonucleotides delivery, as they are resistant to conventional transfection reagents and are dispersed throughout the body, making it difficult to successfully localize or deliver oligonucleotides payloads via systemic administration. In this review, we will survey the latest progress in the field of oligonucleotides based nanomedicine in the heterogeneous group of hematological malignancies with special emphasis on RNA based strategies. We will describe the most advanced non-viral nanocarriers for RNA delivery to malignant blood cells. We will also discuss targeted strategies for cell specific delivery of RNA molecules using nanoparticles and the therapeutic benefit of manipulating gene function in hematological malignancies. Finally, we will focus on the ex vivo, in vivo, and clinical trial strategies, that are currently under development in hematological malignancies - strategies that might increase the arsenal of drugs available to hematologists in the upcoming years.
KW - Hematological malignancies
KW - Nanoparticles
KW - RNAi
KW - Targeted delivery
UR - http://www.scopus.com/inward/record.url?scp=84994626272&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994626272&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2016.07.052
DO - 10.1016/j.jconrel.2016.07.052
M3 - Article
C2 - 27491881
AN - SCOPUS:84994626272
SN - 0168-3659
VL - 244
SP - 149
EP - 156
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -