Targeted delivery of metastasis-specific tumour homing TMTP1 peptide to
non-small-cell lung cancer (NSCLC) using inhalable hybrid
Nano-assemblies
Abstract
Lung cancer is one of the most fatal malignancies, with the highest
death rates (~19%), of which NSCLC type, contributes to
~85%. In the search for new treatments, antimicrobial
peptides have received much attention due to their propensity for
selective destruction of cancer cells. In the current study, we
evaluated the efficacy of metastasis-specific tumour-homing-TMTP1peptide
against lung cancer using inhalable hybrid-nano-assemblies of
PEG–PLGA-copolymer as a carrier for pulmonary delivery which was
assessed for aerodynamic and physicochemical properties, along with
peptide-release profile, physical stability, cellular uptake &
biocompatibility, generation of reactive-oxygen-species, cell migration,
autophagic flux, and apoptotic cell death in A549 lung cancer cells.
Optimization of inhaled dose, lung retention, and efficacy studies was
conducted to evaluate the formulation in NNK (Nicotine-derived
nitrosamine ketone) induced tumour-bearing lung cancer, murine model.
After inhalation, the formulation with nano-scale physiognomies showed
good lung deposition, retention, and metabolic stability. The
inhalable-nano-assemblies have shown enhanced generation of
reactive-oxygen-species with increased autophagy-flux and apoptotic-cell
death. Pre-clinical animal trials show substantial tumour regression by
inhalable-TMTP1-based-nano-formulation with limited side effects. Our
results on metastasis targeting and tumour-homing peptide TMTP1 exhibit
effective tumour targeting and tumour-killing efficacy and provide a
reference for the development of new therapeutics for NSCLC.