BITS Faculty Publications
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Item Immunocyte Derived Exosomes: Insight into the Potential Chemo-immunotherapeutic Nanocarrier Targeting the Tumor Microenvironment(ACS, 2022-12) Mittal, Anupama“Cancer” is a dreadful immune-pathological condition that is characterized by anti-inflammatory and tumorigenic responses, elicited by the infiltrating immune cells in the vicinity of an uncontrollably proliferative tumor in the tumor microenvironment (TME). The TME offers a conducive microenvironment that supports cancer cell survival by modulating the host immune defense. Recent advancement in exosomal research has shown exosomes, originating from immune cells as well as the cancer cells, have immense potential for suppressing cancer progression and survival in the TME. Additionally, exosomes, irrespective of their diverse sources, have been reported to be efficient nanocarriers for cancer therapeutics with the ability for targeted delivery due to their biogenic nature, ease of cellular uptake, and scope for functionalization with biomolecules like peptides, aptamers, targeting ligands, etc. Immune cell-derived exosomes per se have been found efficacious against cancer owing to their immune-stimulant properties (in either naive or antigen primed form) even without loading any of cancer therapeutics or targeting ligand conjugation. Nevertheless, exosomes are being primarily explored as nanovesicular carriers for therapeutic molecules with different loading and targeting strategies, and the synergism between immunotherapeutic behavior of exosomes and the anticancer effect of the therapeutic molecules is yet to be explored. Hence, this review focuses specifically on the possible strategies to modulate the immunological nature of the source immune cells to obtain immune stimulant exosomes and bring these into the spotlight as chemo-immunotherapeutic nanovesicles, that can easily target and modulate the TME.Item Lipopolymeric Nanocarrier Enables Effective Delivery of CRISPR/Cas9 Expressing Plasmid(Wiley, 2023-04) Chitkara, Deepak; Mittal, AnupamaCRISPR/Cas9 has proven its accuracy and precision for gene editing by making a double-strand break at the predetermined site. Despite being a mainstream gene editing tool, CRISPR/Cas9 has limitations for its in vivo delivery due to the physico-chemical properties such as high molecular weight, supranegative charge, degradation in the presence of nucleases, etc. Hereby, a cationic lipopolymer is explored for its efficiency in delivering CRISPR/Cas9 plasmid (pCas9) in vitro and in vivo. The lipopolymer is utilized to form blank cationic nanoplexes having a zeta potential of +15.8 ± 0.7 mV. Being cationic, the blank nanoplexes are able to condense the pCas9 plasmid at a ratio of 1:20 with a complexation efficiency of ≈98% and show a size and zeta potential of ≈141 ± 16 nm and 4.2 mV ± 0.7, respectively. The pCas9-loaded nanoplexes show a transfection efficiency of ≈69% in ARPE-19 cells and show ≈22% of indel frequency, indicating the successful translation of Cas9 protein and guide RNA in the cytosol. Further, they are found to be stable under in vivo environment when given intravenously in Swiss albino mice. These lipopolymeric nanoplexes can be a potential carrier for CRISPR plasmids for genome editing applications.Item RNA Interference Nanotherapeutics for Treatment of Glioblastoma Multiforme(ACS, 2020-09) Chitkara, Deepak; Mittal, AnupamaNucleic acid therapeutics for RNA interference (RNAi) are gaining attention in the treatment and management of several kinds of the so-called “undruggable” tumors via targeting specific molecular pathways or oncogenes. Synthetic ribonucleic acid (RNAs) oligonucleotides like siRNA, miRNA, shRNA, and lncRNA have shown potential as novel therapeutics. However, the delivery of such oligonucleotides is significantly hampered by their physiochemical (such as hydrophilicity, negative charge, and instability) and biopharmaceutical features (in vivo serum stability, fast renal clearance, interaction with extracellular proteins, and hindrance in cellular internalization) that markedly reduce their biological activity. Recently, several nanocarriers have evolved as suitable non-viral vectors for oligonucleotide delivery, which are known to either complex or conjugate with these oligonucleotides efficiently and also overcome the extracellular and intracellular barriers, thereby allowing access to the tumoral micro-environment for the better and desired outcome in glioblastoma multiforme (GBM). This Review focuses on the up-to-date advancements in the field of RNAi nanotherapeutics utilized for GBM treatment.