title: Nucleolin-aptamer therapy in retinoblastoma: molecular changes and mass spectrometry-based imaging.
abstract: Retinoblastoma (RB) is an intraocular childhood tumor which, if left untreated, leads to blindness and mortality. Nucleolin (NCL) protein which is differentially expressed on the tumor cell surface, binds ligands and regulates carcinogenesis and angiogenesis. We found that NCL is over expressed in RB tumor tissues and cell lines compared to normal retina. We studied the effect of nucleolin-aptamer (NCL-APT) to reduce proliferation in RB tumor cells. Aptamer treatment on the RB cell lines (Y79 and WERI-Rb1) led to significant inhibition of cell proliferation. Locked nucleic acid (LNA) modified NCL-APT administered subcutaneously (s.c.) near tumor or intraperitoneally (i.p.) in Y79 xenografted nude mice resulted in 26 and 65% of tumor growth inhibition, respectively. Downregulation of inhibitor of apoptosis proteins, tumor miRNA-18a, altered serum cytokines, and serum miRNA-18a levels were observed upon NCL-APT treatment. Desorption electrospray ionization mass spectrometry (DESI MS)-based imaging of cell lines and tumor tissues revealed changes in phosphatidylcholines levels upon treatment. Thus, our study provides proof of concept illustrating NCL-APT-based targeted therapeutic strategy and use of DESI MS-based lipid imaging in monitoring therapeutic responses in RB.
authors: Department of Nanobiotechnology, Vision Research Foundation, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Chennai, India.|Nanomedicine Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Centre for Molecular and Medical Research (C-MMR), Faculty of Health, Deakin University, Geelong, Australia.
authors: Nithya
authors: N
authors: Subramanian
authors: DST Unit of Nanoscience and Thematic Unit of Excellence, Department of Chemistry, Indian Institute of Technology Madras, Chennai, India.
authors: Amitava
authors: A
authors: Srimany
authors: Nanomedicine Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Centre for Molecular and Medical Research (C-MMR), Faculty of Health, Deakin University, Geelong, Australia.
authors: Jagat R
authors: JR
authors: Kanwar
authors: Nanomedicine Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Centre for Molecular and Medical Research (C-MMR), Faculty of Health, Deakin University, Geelong, Australia.
authors: Rupinder K
authors: RK
authors: Kanwar
authors: Department of Nanobiotechnology, Vision Research Foundation, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Chennai, India.
authors: Balachandran
authors: B
authors: Akilandeswari
authors: Department of Ocular Oncology and Vitreo Retina, Medical Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Pukhraj
authors: P
authors: Rishi
authors: Department of Ocular Oncology and Vitreo Retina, Medical Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Vikas
authors: V
authors: Khetan
authors: Bionivid Technologies, Bangalore, India.
authors: Madavan
authors: M
authors: Vasudevan
authors: DST Unit of Nanoscience and Thematic Unit of Excellence, Department of Chemistry, Indian Institute of Technology Madras, Chennai, India.
authors: Thalappil
authors: T
authors: Pradeep
authors: Department of Nanobiotechnology, Vision Research Foundation, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Chennai, India.|L&T Ocular Pathology Department, Vision Research Foundation, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Chennai, India.
authors: Subramanian
authors: S
authors: Krishnakumar