Subcellular Targeting of Nanoparticles for Cancer Theranostics

The ability of the nanoformulations to reach their final subcellular targets is important for therapeutic efficacy against cancer. Excellent targets in cancer theranostics are generally biological macromolecules at subcellular target level, which play an important role in carcinogenesis. A number of organelle-targeted nanoformulations that can accumulate into specific organelles (cytosol, cytoplasm endosome/lysosome, endoplasmic reticulum (ER), mitochondrion, nucleus, nucleolus, Golgi apparatus, proteasomes and peroxisomes) intra-cancer cells are gaining more attention due to their ability to increase therapy efficacy while minimizing systemic toxicity, avoiding multidrug resistance, stopping recurrence and lowering drug content and other adverse effects. Site-specific drug delivery at the subcellular level could be achieved, for example, by tailoring the properties of nanoformulations/nanoparticles, such as size, shape and surface chemistry. Chemical (e.g., polymeric nanoformulations) or biological (e.g., signal sequences support) delivery methods are available. Technologies that allow multiple signals (e.g., virus-like delivery systems and protein switches, among others) that mimic nature while also allowing for a more sophisticated approach to drug delivery, such as unidirectional targeting to individual organelles, have proven extremely successful for drug therapy. In this chapter, we discuss the most recent advancements as well construction strategies and at the same time the release patterns of various cancer subcellular-targeting nanoformulations, with the goal of providing guidance in the overall design of precise nanoformulations. Aside from that, we discuss future challenges and potential future directions in the hope of improving efficacy and speeding up the translation process to precise nanoformulations.