Advances in carbohydrate polymer-based stimuli-responsive nanocarriers: precision strategies for overcoming multidrug resistance in targeted cancer therapy

Multidrug resistance (MDR) remains a formidable challenge in cancer therapy, often rendering conventional chemotherapeutics ineffective. Recent advances in carbohydrate polymer-based stimuli-responsive nanocarriers have opened new avenues for overcoming MDR while achieving targeted drug delivery. This narrative review highlights the unique properties of carbohydrate polymers, such as biocompatibility, biodegradability, and functional versatility, that make them ideal candidates for designing smart nanocarriers. We discuss molecular engineering strategies to develop stimuli-responsive systems capable of releasing drugs in response to tumor-specific cues like pH gradients, enzymatic activity, or external triggers such as light or temperature. A special emphasis is placed on the mechanisms by which these nanocarriers can overcome MDR, including inhibition of efflux pumps, modulation of the tumor microenvironment, and co-delivery of chemotherapeutics with gene therapies or immunomodulators. Applications in preclinical cancer models are reviewed to showcase their translational potential. This article provides a comprehensive overview of the current state-of-the-art while identifying critical knowledge gaps and emerging trends in carbohydrate polymer-based drug delivery systems for cancer therapy. By focusing on MDR and precision targeting strategies, this review offers a unique perspective that distinguishes it from existing literature.