The development of advanced nano-and micro-carriers for targeted drug delivery has gained significant attention, particularly for cancer therapy. There is a pressing need for smart systems that offer enhanced stability, tuneable properties, and the ability to encapsulate both hydrophilic and hydrophobic agents. A crucial aspect of designing effective drug delivery systems is multicompartmentalization, which enables the co-loading of biological active cargoes with different solubility profiles or functions, ultimately improving their therapeutic efficacy. One promising approach involves pH-responsive polymeric vesicles that exploit the acidic tumour microenvironment to trigger drug release, minimizing off-target effects. Curcumin, a natural polyphenol with potent anti-inflammatory and anticancer properties, holds promise but suffers from poor bioavailability and rapid degradation. Prior methods, including biodegradable microspheres, hydrogels, polymeric nanoparticles, and liposomes, have improved its stability. Encapsulation within pH-responsive polymeric vesicles further enhances its therapeutic potential. Furthermore, tumour progression is often driven by excessive extracellular matrix (ECM) components, such as hyaluronic acid and collagen, which hinder drug penetration. ECM-digesting enzymes can facilitate drug delivery, enhancing efficacy and potentially leading to tumour eradication. Incorporating these enzymes into polymeric nanocarriers allows for sitespecific activation, refining drug delivery precision.