TY - JOUR
T1 - Nanomedicine based approaches for the delivery of siRNA in cancer
AU - Ozpolat, B.
AU - Sood, A. K.
AU - Lopez-Berestein, G.
PY - 2010/1
Y1 - 2010/1
N2 - Small interfering RNA (siRNA) technology holds great promise as a therapeutic intervention for targeted gene silencing in cancer and other diseases. However, in vivo systemic delivery of siRNA-based therapeutics to tumour tissues/cells remains a challenge. The major limitations against the use of siRNA as a therapeutic tool are its degradation by serum nucleases, poor cellular uptake and rapid renal clearance following systemic administration. Several siRNA-based loco-regional therapeutics are already in clinical trials. Further development of siRNAs for anti-cancer therapy depends on the development of safe and effective nanocarriers for systemic administration. To overcome these hurdles, nuclease-resistant chemically modified siRNAs and variety of synthetic and natural biodegradable lipids and polymers have been developed to systemically deliver siRNA with different efficacy and safety profiles. Cationic liposomes have emerged as one of the most attractive carriers because of their ability to form complexes with negatively charged siRNA and high in vitro transfection efficiency. However, their effectiveness as potential therapeutic carriers is limited by potential for pulmonary toxicity. Recently, our laboratories described the use of neutral 1,2-dioleoyl-sn-glycero-3- phosphatidylcholine based nanoliposomes in murine tumour models. We found this approach to be safe and 10- and 30-fold more effective than cationic liposomes and naked siRNA, respectively, for systemic delivery of siRNA into tumour tissues. Here, we review potential approaches for systemic delivery of siRNA for cancer therapy.
AB - Small interfering RNA (siRNA) technology holds great promise as a therapeutic intervention for targeted gene silencing in cancer and other diseases. However, in vivo systemic delivery of siRNA-based therapeutics to tumour tissues/cells remains a challenge. The major limitations against the use of siRNA as a therapeutic tool are its degradation by serum nucleases, poor cellular uptake and rapid renal clearance following systemic administration. Several siRNA-based loco-regional therapeutics are already in clinical trials. Further development of siRNAs for anti-cancer therapy depends on the development of safe and effective nanocarriers for systemic administration. To overcome these hurdles, nuclease-resistant chemically modified siRNAs and variety of synthetic and natural biodegradable lipids and polymers have been developed to systemically deliver siRNA with different efficacy and safety profiles. Cationic liposomes have emerged as one of the most attractive carriers because of their ability to form complexes with negatively charged siRNA and high in vitro transfection efficiency. However, their effectiveness as potential therapeutic carriers is limited by potential for pulmonary toxicity. Recently, our laboratories described the use of neutral 1,2-dioleoyl-sn-glycero-3- phosphatidylcholine based nanoliposomes in murine tumour models. We found this approach to be safe and 10- and 30-fold more effective than cationic liposomes and naked siRNA, respectively, for systemic delivery of siRNA into tumour tissues. Here, we review potential approaches for systemic delivery of siRNA for cancer therapy.
KW - Cancer
KW - Delivery
KW - Gene silencing
KW - Liposomes
KW - Nanovectors
KW - siRNA
UR - http://www.scopus.com/inward/record.url?scp=71949092463&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71949092463&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2796.2009.02191.x
DO - 10.1111/j.1365-2796.2009.02191.x
M3 - Article
C2 - 20059643
AN - SCOPUS:71949092463
VL - 267
SP - 44
EP - 53
JO - Journal of Internal Medicine
JF - Journal of Internal Medicine
SN - 0954-6820
IS - 1
ER -