Genomic DNA Interactions Mechanize Peptidotoxin-Mediated Anticancer Nanotherapy.
Santosh K MisraAaron S Schwartz-DuvalDipanjan PanPublished in: Molecular pharmaceutics (2017)
Host defense peptides (HDPs) are a class of evolutionarily conserved substances of the innate immune response that have been identified as major players in the defense system in many living organisms. Some of the HDPs are also referred to as peptidotoxins, which offer immense potential for anticancer therapy. However, their therapeutic potential is yet to be fully translated mainly due to their off-target toxicity. Here we show that their nanoenabled delivery may become beneficial in controlling their delivery in intracellular space. We introduced an amphiphilic polymer to synthesize a well-defined, self-assembled, rigid-cored polymeric nanoarchitecture for controlled delivery of three model peptidotoxins, i.e., melittin, TSAP-1, and a negative control peptide of synthetic origin. Interestingly, our results revealed strong interaction of peptidotoxins with duplex plasmid DNA. Extensive biophysical characterization (UV-vis spectroscopy, gel electrophoresis, MTT assay, and flow assisted cell sorting) experimentally verified that peptidotoxins were able to interact with genomic DNA in vitro and in turn influence the cancer cell growth. Thus, we unraveled that, through genomic DNA regulation, peptidotoxins can play a role in cell cycle regulation and exert their anticancer activities.
Keyphrases
- circulating tumor
- single molecule
- cell cycle
- immune response
- cell free
- copy number
- single cell
- cell proliferation
- nucleic acid
- escherichia coli
- high resolution
- stem cells
- drug delivery
- cell therapy
- living cells
- circulating tumor cells
- oxidative stress
- crispr cas
- drinking water
- high throughput
- transcription factor
- dna methylation
- mass spectrometry
- inflammatory response
- sensitive detection
- mesenchymal stem cells
- quantum dots
- solid state
- gram negative
- amino acid