Curcumin-Integrated Smart Nanocarriers: A Multi-Stimuli-Responsive Platform for Targeted Delivery of 5-Fluorouracil in Cancer Therapy

Conventional chemotherapy for cancer treatment often suffers from limitations such as non-specificity, multidrug resistance (MDR), poor drug circulation, and rapid metabolism. Designing a nanocarrier system with a targeting ability may aid in efficiently delivering chemotherapeutic agents with high specificity. This work deals with synthesis of a biotin-conjugated nanomicellar carrier derived from curcumin bearing pH-, enzyme-, and redox-responsive linkages. It is preliminarily characterized using FTIR, 1 H NMR, and 13 C NMR, and the size and morphology are studied using TEM and DLS measurements. The synthesized amphiphilic polymer self-assembles into spherical micelles having an average diameter of 80 nm. It exhibits a drug loading efficiency (DLE) of 51% and stimuli-triggered drug release in response to variation in pH, enzyme, and glutathione concentration. It shows a complete and sustained drug release profile in vitro under a simulated tumor microenvironment (TME). Encapsulation enhances potency, lowering the IC 5 0 to 49.5 μg/mL (MCF-7) and 46.3 μg/mL (HepG2) versus 91.82 and 76.3 μg/mL for the free drug with results further supported by in vivo hepatocarcinoma mouse models.