Dual pH/temperature-responsive β-cyclodextrin-grafted cellulose nanocrystals for co-delivery of methotrexate and curcumin to MCF-7 cells

The development of smart natural delivery systems that can deliver several chemotherapeutics in a controlled manner is a promising idea to enhance cancer treatment efficacy. In this study, we designed and synthesized a smart, dual pH- and thermo-responsive nanocarrier system based on β-CD-g-BCN, which was further functionalized with MSP and copolymerized with NIPAAm and DMAEMA to yield the final β-CD-g-BCN@MSP@PND formulation. The nanocarriers indicated efficient encapsulation of two anticancer agents, MTX and CUR, with encapsulation efficiencies of 64.5% and 87%, respectively. Successful functionalization and thermal stability were validated by characterization using FTIR, FESEM, TEM, DLS, zeta potential, and TGA. The nanoparticles exhibited sharp LCST behavior (~ 40.5 °C), which facilitates temperature-sensitive drug release. Improved drug release under acidic (pH 5.8) and hyperthermic (40 °C) conditions, simulating the tumor, was confirmed by in vitro release studies. Based on cytotoxicity studies, the MTX/CUR-loaded system had strong synergistic effects (CI < 0.1) on MCF-7 cells, while blank nanoparticles showed negligible toxicity. The time-dependent cellular uptake of RhB-labeled nanocarriers was validated by fluorescence microscopy. Overall, the prepared dual-responsive nanocarrier shows great promise for effective breast cancer treatment. However, this study is limited to in vitro evaluations, and further in vivo studies are required to confirm the therapeutic potential of the developed nanocarrier.