In Vitro and In Vivo Biological Evaluation of O-Carboxymethyl Chitosan Encapsulated Metformin Nanoparticles for Pancreatic Cancer Therapy
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In vitro anticancer effect and in vivo biodistribution and biocompatibility of metformin encapsulated O-Carboxymethyl chitosan nanoparticles were evaluated for its application as pancreatic cancer therapy.
In vitro studies such as cell migration assay, clonogenic assay, cell cycle analysis and qRT-PCR analysis were done in pancreatic cancer cells (MiaPaCa-2) treated with O-CMC-metformin NPs for evaluating its anticancer potential. In vivo biodistribution studies were carried out by NIR imaging of O-CMC-metformin NPs after tagging it with ICG. In vivo biocompatibility of the NPs was assessed by histopathology analysis of organs from mice administered with the NPs.
In vitro cell migration assay showed marginal effect of NPs on migration property of pancreatic cancer cells (MiaPaCa-2). In vitro clonogenic assay established that the O-CMC-metformin NPs reduced colony formation ability of the cancer cells. While cell cycle analysis showed that the O-CMC-metformin NPs had only minor effect on progression of cell cycle in the cancer cells. qRT-PCR analysis exhibited reduced mRNA expression of p21, vanin 1 and MMP9 in pancreatic cancer cells treated with the nanoparticles. In vivo NIR imaging study showed normal biodistribution pattern of the intravenously injected O-CMC-metformin NPs suggesting normal clearance rate of nanoparticles and no adverse toxicity to the organs.
The biocompatible O-CMC-metformin NPs with anticancer potential and capability for normal biodistribution can be beneficial for the treatment of pancreatic cancer.
Key Wordscancer therapy clonogenecity drug delivery gene expression metformin migration O-CMC nanoparticles pancreatic cancer
Acknowledgments and Disclosures
The authors are thankful to Department of Science and Technology (DST), Government of India, for their financial support under Fast Track SERC project (Ref.No.: SERC 0558/2009/LS). K. S. Snima is grateful to Council of Scientific and Industrial Research (CSIR), India, for providing Senior Research Fellowship (09/963 (0030)/2 K 13-EMK-I) for carrying out her research work. We thank Dr. A.K.K. Unni, Dr. P. Reshmi, and Mr. Sunil Kumar O. R for the support and help they extended to carry out in vivo experiments in the Central animal house facility, Amrita Institute of Medical Science and Research centre, Kerala, India. We are also grateful to Mrs. Sreerekha P. R and Dr. G. Siddaramana Gowd for there helps in FACS analysis and in vivo NIR imaging. We thank Amrita Centre for Nanosciences and Molecular Medicine for the infrastructure support.
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