Nanomaterials for subcellular organelle targeting: unlocking new avenues for enhanced therapeutic effectiveness

Subcellular organelle targeting is changing the way nanomedicine is designed, moving the field beyond simple cellular entry towards more precise intracellular localization, controlled cargo release, and functional activity within disease-relevant compartments. This review critically discusses nanomaterial-based strategies for targeting the nucleus, mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus, and cytoskeleton-associated trafficking pathways. Its main novelty is the use of a cross-organelle, mechanism-based framework that links nanocarrier physicochemical properties with intracellular transport biology, rather than examining each organelle or delivery platform separately. Nanocarriers are compared according to their targeting mechanisms, cargo compatibility, therapeutic potential, and translational limitations. Particular attention is given to nuclear import mediated by NLS-, CPP/TAT-, and aptamer-based strategies; mitochondrial delivery shaped by membrane potential, membrane fusion, and redox-responsive release; lysosomal targeting for pH- and enzyme-activated therapies; and ER/Golgi-directed delivery through retrograde trafficking, retention motifs, and modulation of stress-related pathways. The review also focus on stimuli-responsive release, biomimetic surface engineering, extracellular vesicle scalability, CRISPR/Cas delivery, base and prime editing, and targeted protein degradation, all of which may support more programmable forms of intracellular therapy. Importantly, it separates true organelle localisation from transient trafficking or non-specific perinuclear accumulation, emphasising the need for stronger and more reliable validation methods.