<p>This study aimed to synthesize, characterize, and evaluate the biological activity of poloxamer F108-conjugated usnic acid nanomicelles (UANM). The newly syntehsized conjugate system comprises three components: (1) the hydrophobic drug usnic acid (UA), (2) a linker, succinic anhydride (SA), facilitating conjugation with amphiphilic polymers, and (3) the tri-block polymer Pluronic F108 (F108). The F108-UA conjugate (UANM), synthesized via succinyl linkage, self-assembled into nanomicelles with a critical micelle concentration (CMC) of 200&#xa0;µg/mL. The nanomicelles were comprehensively characterized using FTIR, ¹H-NMR, DLS, TEM, DSC, and PXRD analyses. The UANM exhibited a zeta size of 101.45 ± 1.2&#xa0;nm, PDI of 0.211 ± 0.003, and zeta potential of -11.5 ± 0.35 mV, with a uniform, spherical morphology confirmed by TEM analysis. DSC and PXRD analyses indicated that UA was molecularly dispersed in an amorphous state within the nanocarriers. The controlled release of the drug was investigated in the following media: pH 1.2, 6.8, 5.0, and 7.4. The UANM bioconjugate micelles demonstrated pH-responsive behaviour, providing stability in normal tissues and controlled drug release in tumour cancer cells (pH 5.0), making them a potential drug carrier for targeted cancer therapy. The anticancer activity of UANM was evaluated in H1299 human non-small cell lung carcinoma using MTT, trypan blue, apoptosis, and wound healing assays. The UANM exhibited superior efficacy compared to free UA, reducing cell viability and inhibiting migration by 54% after 48&#xa0;h. The IC₅₀ value of UANM (9.1 ± 0.35 µM) was markedly lower than that of pure UA (27.6 ± 0.25 µM), and the nanomicelles induced higher apoptosis. Overall, UA-conjugated nanomicelles enhanced solubility, stability, and tumour-selective drug release, overcoming the limitations of free UA and demonstrating strong potential as a targeted delivery system for lung cancer therapy.</p> Graphical abstract <p></p>