The dynamic and versatile phytochemicals seen in nature are inspiring for the next generation of eco-friendly cancer therapeutics. Integrating phytochemicals in nanomedicine is an unorthodox approach that might revolutionize safe cancer therapy. Herein, we reported the synergistic enhancement of carboplatin (Cp), a second-generation platinum-based anticancer drug, anti-colorectal cancer efficacy through pH-sensitive plant-based nanoparticles formulated using naturally derived Frankincense oleo-gum resin extracted from the trunks of Boswellia sacra trees. Nanoparticles were prepared via the nanoprecipitation method, loaded with Cp, and coated with the positively charged chitosan (CS) for enhanced cell interaction, yielding Cp@CS/BME NPs with an average size of 160.2 ± 4.6 nm and a zeta potential of 12.7 ± 1.5 mV. In vitro release studies revealed a pH-sensitive release profile, with higher release rates at pH 5.4 than pH 7.4, highlighting the potential for targeted drug delivery in acidic tumor environments. The release kinetics of Cp@CS/BME NPs were analyzed using several mathematical models to understand the mechanism and rate of drug release under different pH conditions. The Higuchi model exhibited the highest correlation coefficient for both pH conditions, indicating that diffusion was the primary mechanism governing the release of Cp from the CS/BME NPs. Cellular uptake assessment showed a significant increase in Cp accumulation in both HT-29 and Caco-2 cells treated with Cp@CS/BME NPs compared to those treated with free Cp over the designated incubation periods. The in vitro studies showed potent cytotoxicity against HT-29 and Caco-2 colorectal cancer cell lines with significant apoptotic effects, a significant increase in the sub-G1 phase, and a marked decrease in the G1 phase population in both cell lines after treatment with Cp@CS/BME NPs. Further gene expression analysis demonstrated a substantial downregulation of the anti-apoptotic gene Bcl-2 and an upregulation of pro-apoptotic genes Bax, PUMA, and BID. To this end, our study would pave the way for employing versatile phytochemicals as future nanomedicines to enhance the therapeutic efficacy of chemotherapeutic agents at low doses while limiting their side effects.

Nada Sedky

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