<p>Colorectal cancer (CRC) continues to rank among the most prevalent and clinically significant malignancies on a global scale. Traditional chemotherapy often leads to systemic drug dispersion, culminating in deleterious off-target effects on healthy, non-malignant tissues. This highlights the critical need for designing targeted drug delivery platforms that improve therapeutic accuracy by limiting off-target exposure. In this context, a temperature and pH responsive co-polymer, Alg-g-P(NIPAAm-co-NVP), was fabricated and evaluated for its potential to deliver Capecitabine specifically to colorectal tumour sites. Alg-g-P(NIPAAm-co-NVP) co-polymers were synthesized and 2² factorial design was employed to optimize sodium alginate and NVP concentrations to achieve tumour-specific responsiveness for co-polymer. Capecitabine was loaded into the optimized formulation and assessed for release behaviour, cytotoxicity and stability studies. Drug release studies revealed significantly enhanced release under tumour-like pH and temperature conditions (~ 82.62%) compared to physiological conditions (~ 38.24%), with MTT assay results corroborating increased drug release in the tumour microenvironment as CAP-loaded nanoparticles exhibited lower cytotoxicity than free Capecitabine (IC₅₀; 30 ± 1.2&#xa0;µg /mL), under physiological conditions (IC₅₀; 27 ± 1.4&#xa0;µg/mL), but higher cytotoxicity in the tumour-like environment (IC₅₀;23 ± 2.1&#xa0;µg/mL). The biocompatibility of the co-polymer and Capecitabine-loaded nanoformulation was validated via MTT assay using human fibroblast (NIH) cell lines. Stability studies indicated that the optimized formulation exhibits excellent stability when stored at 4–8 ± 2&#xa0;°C. The developed Alg-g-P(NIPAAm-co-NVP) nanoparticles exhibit considerable potential for Capecitabine to achieve tumour specific targeting, offering an innovative strategy for controlled and site-specific delivery in oncology.</p> Graphical abstract <p></p>