Core-shell nanostructures are promising platforms for
combination drug delivery. However, their complicated synthesis process, poor stability, surface engineering, and low biocompatibility are major hurdles. Herein, a
carboxymethyl chitosan-coated
poly(lactide-co-glycolide) (cmcPLGA) core-shell nanostructure is prepared via a simple one-step nanoprecipitation self-assembly process. Engineered core-shell nanostructures are tested for combination delivery of loaded
docetaxel and
doxorubicin in a
cancer-mimicked environment. The drugs are compartmentalized in a shell (
doxorubicin, Dox) and a core (
docetaxel, Dtxl) with loading contents of ∼1.2 and ∼2.06%, respectively.
Carboxymethyl chitosan with both
amine and carboxyl groups act as a polyampholyte in diminishing ΞΆ-potential of nanoparticles from fairly negative (-13 mV) to near neutral (-2 mV) while moving from a physiological pH (7.4) to an acidic
tumor pH (6) that can help the nanoparticles to accumulate and release the
drug on-site. The dual-
drug formulation was found to carry a clinically comparable 1.7:1 weight ratio of Dtxl/Dox, nanoengineered for the sequential release of Dox followed by Dtxl. Single and engineered combinatorial nanoformulations show better growth inhibition toward three different
cancer cells compared to free
drug treatment. Importantly, Dox-Dtxl cmcPLGA nanoparticles scored synergism with combination index values between 0.2 and 0.3 in BT549 (
breast ductal carcinoma), PC3 (
prostate cancer), and A549 (
lung adenocarcinoma) cell lines, demonstrating significant cell growth inhibition at lower
drug concentrations as compared to single-drug control groups. The observed promising performance of dual-
drug formulation is due to the G2/M phase arrest and apoptosis.