Organelle-targeted precision cancer theranostics: From molecular design to NIR-II imaging

The disruption of organelle homeostasis is a hallmark in the process of tumor occurrence and development. The abnormalities of these subcellular structures not only indicate the pathological state of the body tissue, but also provide actionable targets for clinical intervention. In recent years, organelle targeted fluorescence imaging technology has shown unique advantages in tumor identification, subcellular localization and dynamic function monitoring. In this review, we systematically summarize the latest progress of organelle-targeted theranostics platforms for precise cancer diagnosis and treatment, focusing on five major organelles: Mitochondria (Mt), Lysosomes, Endoplasmic reticulum (ER), Nucleus and Golgi apparatus (GA). We discussed the molecular design strategies for these platforms to achieve targeted organelle diagnosis imaging. At the same time, we focused on comparing the activation mechanism of targeting motifs, imaging platforms, and advanced strategies such as Aggregation-Induced Emission (AIE), ratiometric imaging and signal amplification. These common strategies jointly ienhance the accuracy of tumor diagnosis. In addition, this review explores how organelle imaging information has evolved from a simple localization imaging tool to the basis for tumor treatment decision-making, including determining the best treatment window, regulating probe activation, monitoring intracellular transport, evaluating organelle damage, multi-organelle cascade therapies, and promoting immunogenic cell death. In addition to these cellular strategies, the emergence of Near-infrared II (NIR-II) fluorescence imaging provides the latest and key technical advantages for deep tissue tracking of biological distribution, tumor retention and treatment timing in vivo. This review aims to overcome the technical challenges of insufficient tissue penetration depth and insufficient targeted specificity in the field of tumor diagnosis and treatment, so as to promote the development of high-efficiency, low-toxic and accurate tumor platforms and accelerate their clinical translation.