A Novel Combinational Nanodrug Delivery System Induces Synergistic Inhibition of Lung Adenocarcinoma Cells In vitro

Background: The combination of two or more therapeutic drugs is an attractive approach to improve the treatment of experimental tumors. Leveraging nanocarriers for combinational drug delivery can allow control over drug biological fate and promote co-localization in the same area of the body. However, there are certain concerns regarding the biodegradability and potential long-term toxicity arising from these synthetic nanoscale carriers. Objective: Our aim was to develop a combinational nanodrug delivery system formed by self-assembling of amphiphilic drug molecules, minimizing potential toxicities associated with using additional synthetic nanocarriers. Methods: A novel prodrug chlorambucil gemcitabine conjugate was synthesized, this prodrug was used for the encapsulation of an additional hydrophobic anticancer drug paclitaxel, taking the form of combinational nanodrugs. Particle size and zeta potential were evaluated, cytotoxicity assay and apoptosis/cell cycle analysis were also performed to validate the anticancer efficacy of the combinational nanodrugs. Results: The combinational nanodrugs were acquired by means of nanoprecipitation. In A549 lung adenocarcinoma cell line, cellular assays revealed that co-delivery of low dosage paclitaxel with chlorambucil gemcitabine conjugate can act synergistically to inhibit cell growth and induce accumulation of cells in the G2/M phase with a concomitant decrease in G0/G1 compartment. Conclusion: Chlorambucil gemcitabine conjugate and paclitaxel can co-assemble into composite nanoparticles by a nanoprecipitation process and the resulting combinational nanodrugs showed a synergistic anticancer effect. This synthetic nanocarrier-free approach might broaden the nanodrug concept and have potential in cancer therapy.