Sushmita Chatterjee

Tel Aviv University | TAU · Department of nanotechnology

Lipid nanoparticles (LNPs) have recently emerged as a powerful and versatile clinically approved platform for nucleic acid delivery, specifically for mRNA vaccines. A major bottleneck in the field is the release of mRNA-LNPs from the endosomal pathways into the cytosol of cells where they can execute their encoded functions. The data regarding the...

Ionizable lipid‐based nanoparticles (LNPs) are the most advanced non‐viral drug delivery systems for RNA therapeutics and vaccines. However, cell type‐specific, extrahepatic mRNA delivery is still a major hurdle, hampering the development of novel therapeutic modalities. Herein, a novel ionizable lipid library is synthesized by modifying hydrophobi...

The potential of microtubule-associated protein targets for cancer therapeutics remains largely unexplored due to the lack of target-specific agents. Here, we explored the therapeutic potential of targeting cytoskeleton-associated protein 5 (CKAP5), an important microtubule-associated protein, with CKAP5-targeting siRNAs encapsulated in lipid nanop...

Cell mitosis is an attractive target for cancer therapy. Presently, anti-mitotic drugs are limited to tubulin binding agents and kinase inhibitors. While there is a long list of potential microtubule associated protein targets that play an important role in tubulin function, their therapeutic potential remains largely unexplored due to the lack of...

Immunotherapy In article number 2106350, Dan Peer and co‐workers propose a strategy to boost chemo‐immunotherapy by using a dual cell‐targeted lipid nanotherapeutic boost. With this approach, chemo‐induced immunogenic cancer cell death is increased, tumor myeloid cell is reprogrammed, and cytotoxic T cell is recruited, which consequently improves r...

Chemo-immunotherapy is a combination of "standard-of-care" chemotherapy with immunotherapy and it is considered the most advanced therapeutic modality for various types of cancers. However, many cancer patients still poorly respond to current regimen of chemo-immunotherapy and suggest nanotherapeutics as a boosting agent. Recently, heme oxygenase-1...

Currently there are no specific therapies addressing the distinctive biology of human papillomavirus (HPV)-induced cancer approved for clinical use. Short interfering RNA (siRNA) has much potential for therapeutic manipulation of HPV E6/E7 oncoproteins. Lipid-based nanoparticles (LNPs) can be utilized for systemic transportation and delivery of siR...

Lipid nanoparticles encapsulating two different small interfering ribonucleic acids are developed that block essential pathways for cancer cell survival. Targeting of metastasized ovarian cancer cells is further enhanced by coating nanoparticles with hyaluronan. Robust gene silencing in key tissues involved in ovarian cancer pathophysiology in an a...

Ovarian cancer is an aggressive tumor owing to its ability to metastasize from stage II onward. Herein, lipid nanoparticles (LNPs) that encapsulate combination of small interfering RNAs (siRNAs), polo‐like kinase‐1 (PLK1), and eukaryotic translation‐initiation factor 3c (eIF3c), to target different cellular pathways essential for ovarian cancer pro...

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western populations. Therapies such as mRNA and siRNA encapsulated in lipid nanoparticles (LNPs) represent a clinically advanced platform and are utilized for a wide variety of applications. Unfortunately, transfection of RNA into CLL cells remains a formidable challenge and a...

In article number 1906128, Dan Peer and co‐workers describe the design and synthesis of novel ionizable lipids based on a linker strategy. The lipids are formulated into lipid nanoparticles and are screened for their gene silencing efficacies in cell‐culture models in vitro. Potent lipids are identified and analyzed for in vivo gene silencing effic...

Lipid nanoparticles (LNPs) are the most advanced nonviral platforms for small interfering RNA (siRNA) delivery that are clinically approved. These LNPs, based on ionizable lipids, are found in the liver and are now gaining much attention in the field of RNA therapeutics. The previous generation of ionizable lipids varies in linker moieties, which g...

Failure of cancer therapies in clinical settings is often attributed to lack of relevant tumor model and pathological heterogeneity across tumor types in the clinic. The objective of this study was to develop a robust in vivo tumor model that better represents clinical tumors for the evaluation of anti-cancer therapies. We successfully developed a...

Chasing an intriguing biological question on the disparity of sodium iodide symporter (NIS, officially known as SLC5A5) expression and function in the clinical scenario of breast cancer, this study addresses key molecular defects involved. NIS in cancer patients has primarily been recorded to be a cytoplasmic protein, thus limiting the scope for ta...

Purpose: Aberrant expression of human sodium iodide symporter (NIS) in breast cancer (BC) is well documented but the transcription factors (TF) regulating its aberrant expression is poorly known. We identify the presence of three p53 binding sites on the human NIS promoter sequence by conducting genome-wide TF analysis, and further investigate the...

Radiosensitization using either metformin or 2-deoxy-d-glucose (2-DG) in various cancer cells has been reported. The present study reveals novel information on combining these drugs to enhance radiosensitization effect in breast cancer (BC) cells. Responses to low-dose Cobalt60 radiation, as well as a newly emerged radioiodine therapy target for BC...

(A) Foci assay images from Figure 5 (MCF-7 plain cells treated with 131I and its combination with radio sensitizers) showing foci staining with dylight 633 secondary antibody in red channel, nucleus stained with DAPI in blue channel, and merged image showing colocalization of foci with nucleus. Scale bars represent 10 μm. (B) Quantification of foci...

Cytotoxic effect of 2-DG and metformin in (A) MCF-7 and (B) MDA MB 231 breast cancer cell lines. Abbreviations: 2-DG, 2-deoxy-d-glucose; Met F, metformin.

Effect of Cobalt60 radiation and it’s combination with 2-DG and Met F on foci formation in MCF-7 cells. Notes: (A) Foci assay images from cells treated with Cobalt60 radiation and combination with radio sensitizers showing foci staining with dylight 633 secondary antibody in red channel, nucleus stained with DAPI in blue channel, and merged image s...

Effect of 2-DG, metformin, and their combination with Cobalt60 radiation on MDA MB 231 cells. Notes: (A and B) MDA MB231 cells were treated with different dose of 2-DG or metformin, with or without radiation exposure for 24 hours, and clonogenic assay was performed. (C) Combination of 5 mM 2-DG and 4 mM metformin with 2 Gy radiation dose showing fu...

(A) Foci assay images from Figure 4 (MCF-7 NIS cells treated with 131I and its combination with radio sensitizers) showing foci staining with dylight 633 secondary antibody in red channel, nucleus stained with DAPI in blue channel, and merged image showing colocalization of foci with nucleus. Scale bars represent 10 μm. (B) Quantification of foci f...

Molecular imaging provides the ability of simultaneous visual and quantitative estimation of long term gene expression directly from living organisms. To reveal the kinetics of gene expression by imaging method, often sustained expression of the transgene is required. Lentiviral vectors have been extensively used over last fifteen years for deliver...

Long chain lipid (LCL) based Tamoxifen loaded nanostructured lipid carriers (Tmx-NLC) meant to target intestinal lymphatic systems (ILS) was developed and characterized previously. The aim of the present work was to evaluate in vitro efficacy of developed Tmx-NLC against breast cancer cell lines and to confirm the hypothesis of targeting ILS after...

A one day pre-conference workshop on "molecular imaging in oncology" was held on November 21st, 2012 ahead of the International conference on radiation biology 2012 at Advanced Centre for Treatment Research and Education in Cancer (ACTREC), TMC, Navi Mumbai, India. The aim of the workshop was to illustrate various applications and the fundamentals...

Background: Human sodium iodide symporter (hNIS) gene over-expression is under active consideration worldwide as an alternative target molecule for breast cancer (BC) diagnosis and targeted radio-iodine treatment. However, the field demands better stratified analysis of endogenous hNIS expression across major BC subtypes. Therefore, we have analyz...

Images captured using higher magnification can assign correct scoring by reducing the averaging effect contributed from the stomal areas. A) Analysis of image score using a 20X image of a case where low tumor cells were present. After color deconvolution, the macro was used on the DAB image to plot a histogram profile and the score was determined a...

Summary of IHC scores for hNIS expression in different subtypes of breast cancer. (DOCX)