Boosting Cancer Therapy with Organelle-Targeted Nanomaterials.

The ultimate goal of cancer therapy is to eliminate malignant tumors while causing no damage to normal tissues. In the past decades, numerous nanoagents have been employed for cancer treatment because of their unique properties over traditional molecular drugs. However, lack of selectivity and unwanted therapeutic outcomes have severely limited the therapeutic index of traditional nanodrugs. Recently, a series of nanomaterials that can accumulate in specific organelles (nucleus, mitochondrion, endoplasmic reticulum, lysosome, Golgi apparatus) within cancer cells have received increasing interest. These rationally designed nanoagents can either directly destroy the subcellular structures or effectively deliver drugs into the proper targets, which can further activate certain cell death pathways, enabling them to boost the therapeutic efficiency, lower drug dosage, reduce side effects, avoid multidrug resistance, and prevent recurrence. In this Review, the design principles, targeting strategies, therapeutic mechanisms, current challenges, and potential future directions of organelle-targeted nanomaterials will be introduced.