Biologically responsive nanotechnologies have attracted tremendous attentions for controlled delivery of therapeutic molecules and the development of precision medicines. Dr. Shi and his team have recently designed various bioresponsive nanoparticle platforms to tackle the challenges associated with systemic RNA delivery to tumor cells, such as enzymatic degradation, rapid elimination by renal excretion or the mononuclear phagocyte system, and insufficient tumor penetration, cellular uptake and endosomal escape. For example, a new generation of lipid-polymer hybrid nanoparticles has been rationally developed using a unique self-assembly technology, which are small and responsive to serum albumin, can efficiently encapsulate siRNA, and exhibit long blood circulation, high tumor accumulation, and negligible in vivo side effects. These hybrid nanoparticles have now been applied to the delivery of mRNAs for cancer therapy and vaccine development. Furthermore, Dr. Shi’s team has recently generated bioinspired ROS/RNS-scavenging melanin nanomaterials with multi-antioxidative and anti-inflammatory activities for controlling ischemic brain injury. We expect that bioresponsive nanotechnologies could become clinically useful tools for the development of novel therapeutics for different diseases.