Assessment of drug delivery and anticancer potentials of nanoparticles-loaded siRNA targeting STAT3 in lung cancer, in vitro and in vivo.
Activation of signal transducer and activator of transcription3 (STAT3) is a hallmark of several types of cancer. Failure to inhibit STAT3 expression by injection of siRNA for STAT3 directly to Balb/c mice led us to adopt alternative means. We formulated nanoparticle-based encapsulation of siRNA (NsiRNA) with polyethylenimine (PEI) and poly(lactide-co-glycolide) (PLGA) and characterized them. The siRNA treated and NsiRNA-treated cells were subjected separately to different assay systems. We also checked if NsiRNA could cross the blood brain barrier (BBB). Cell viability reduced dramatically in A549 cells after NsiRNA administration (23.89% at 24 h), thereby implicating considerable silencing of STAT3 by NsiRNA, but not after siRNA administration. Compared to controls, a significant decrease in expression of IL-6 and the angiogenic factor (VEGF) and increase in Caspase 3 activity was observed with corresponding regression in tumor growth in mice treated with NsiRNA. NsiRNA induced apoptosis of cells and arrested cells at G1/G0 stage, both in vitro and in vivo. Apoptosis was also verified by Annexin-V-FITC/Propidium-iodide staining. NsiRNA could cross blood brain barrier. Overall results revealed PEI-PLGA to be a promising carrier for delivery of siRNA targeting STAT3 expression, which can be utilized as an effective strategy for cancer therapy.
Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India.
Jayeeta
J
Das
Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India.
Sreemanti
S
Das
Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India.
Avijit
A
Paul
Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India.
Asmita
A
Samadder
Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India.
Soumya Sundar
SS
Bhattacharyya
Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India. Electronic address: prof_arkb@yahoo.co.in.
Anisur Rahman
AR
Khuda-Bukhsh
D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D005434:Flow Cytometry; D020868:Gene Silencing; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000008:administration & dosage*; D011094:Polyethyleneimine / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000494:pharmacology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D015850:Interleukin-6; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D011100:Polyglycolic Acid; D012313:RNA; D011094:Polyethyleneimine; D053148:Caspase 3
Blood brain barrier; Drug delivery; Lung cancer; STAT3 siRNA nanoparticle; mice