Assessment of drug delivery and anticancer potentials of nanoparticles-loaded siRNA targeting STAT3 in lung cancer, in vitro and in vivo

Jayeeta Das; Sreemanti Das; Avijit Paul; Asmita Samadder; Soumya Sundar Bhattacharyya; Anisur Rahman Khuda-Bukhsh

doi:10.1016/j.toxlet.2014.01.009

Assessment of drug delivery and anticancer potentials of nanoparticles-loaded siRNA targeting STAT3 in lung cancer, in vitro and in vivo

Jayeeta Das, Sreemanti Das, Avijit Paul, Asmita Samadder, Soumya Sundar Bhattacharyya, Anisur Rahman Khuda-Bukhsh

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	454-466
Number of pages	13
Journal	Toxicology Letters
Volume	225
Issue number	3
DOIs	https://doi.org/10.1016/j.toxlet.2014.01.009
State	Published - 21 Mar 2014
Externally published	Yes

Keywords

Blood brain barrier
Drug delivery
Lung cancer
Mice
STAT3 siRNA nanoparticle

ASJC Scopus subject areas

Toxicology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.toxlet.2014.01.009

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@article{53e16e28ef20488388b1ecd1f9260802,

title = "Assessment of drug delivery and anticancer potentials of nanoparticles-loaded siRNA targeting STAT3 in lung cancer, in vitro and in vivo",

abstract = "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.",

keywords = "Blood brain barrier, Drug delivery, Lung cancer, Mice, STAT3 siRNA nanoparticle",

author = "Jayeeta Das and Sreemanti Das and Avijit Paul and Asmita Samadder and Bhattacharyya, {Soumya Sundar} and Khuda-Bukhsh, {Anisur Rahman}",

note = "Funding Information: This work was financially supported by a grant sanctioned to Prof. A. R. Khuda-Bukhsh, Department of Zoology, University of Kalyani, Kalyani 741235, India by Boiron Laboratory , Lyon, France. We are also thankful to Dr. Kumaresh Ghosh, Mr. Tanmoy Sarkar, Department of Chemistry. Thankful acknowledgements are made to Dr. Tarak Das Basu and Ms. Ruchira Chakraborty, Department of Biochemistry, University of Kalyani, India. We are thankful to Dr T.C. Nag and Mr. Sandeep Arya, Department of Anatomy, AIIMS, India for TEM. We are also thankful to Dr. Anindita Chakraborty UGC-DAE Consotorium, Jadavpur University, Kolkata. We are grateful to Dr. Suvendra Nath Bhattacharyya and Mr. Diptadeep Sarkar, IICB, Kolkata for Confocal microscopy.",

year = "2014",

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doi = "10.1016/j.toxlet.2014.01.009",

language = "English",

volume = "225",

pages = "454--466",

journal = "Toxicology Letters",

issn = "0378-4274",

publisher = "Elsevier BV",

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T1 - Assessment of drug delivery and anticancer potentials of nanoparticles-loaded siRNA targeting STAT3 in lung cancer, in vitro and in vivo

AU - Das, Jayeeta

AU - Das, Sreemanti

AU - Paul, Avijit

AU - Samadder, Asmita

AU - Bhattacharyya, Soumya Sundar

AU - Khuda-Bukhsh, Anisur Rahman

N1 - Funding Information: This work was financially supported by a grant sanctioned to Prof. A. R. Khuda-Bukhsh, Department of Zoology, University of Kalyani, Kalyani 741235, India by Boiron Laboratory , Lyon, France. We are also thankful to Dr. Kumaresh Ghosh, Mr. Tanmoy Sarkar, Department of Chemistry. Thankful acknowledgements are made to Dr. Tarak Das Basu and Ms. Ruchira Chakraborty, Department of Biochemistry, University of Kalyani, India. We are thankful to Dr T.C. Nag and Mr. Sandeep Arya, Department of Anatomy, AIIMS, India for TEM. We are also thankful to Dr. Anindita Chakraborty UGC-DAE Consotorium, Jadavpur University, Kolkata. We are grateful to Dr. Suvendra Nath Bhattacharyya and Mr. Diptadeep Sarkar, IICB, Kolkata for Confocal microscopy.

PY - 2014/3/21

Y1 - 2014/3/21

N2 - 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.

AB - 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.

KW - Blood brain barrier

KW - Drug delivery

KW - Lung cancer

KW - Mice

KW - STAT3 siRNA nanoparticle

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M3 - Article

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IS - 3

ER -

Assessment of drug delivery and anticancer potentials of nanoparticles-loaded siRNA targeting STAT3 in lung cancer, in vitro and in vivo

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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