Proteins, enzymes, and peptides have long been recognized as valuable therapeutic agents, particularly in oncology. However, their complex chemical structures render them more sensitive than smaller chemotherapeutic drugs. As a result, their administration and pharmacokinetics have been the subject of extensive research to overcome limitations associated with premature clearance and degradation. The pharmaceutical industry has come up with various solutions, such as partial modification of their structure or their incorporation into targeted drug carrier systems. In this context, the advancement of nanotechnology has offered a promising strategy for the efficient delivery of these sensitive yet potent biopharmaceuticals to solid tumors, while enabling control of their action in response to specific stimuli. The versatility of nanoscience has endowed these nanovehicles with an expanding array of tailored features, enhancing their capabilities through controlled chemical composition and surface functionalization, and optimizing their interaction with both the immune system and the tumor microenvironment. This review compiles cutting‐edge research articles to explore the full potential of stimuli‐responsive nanocarriers in protein‐based cancer treatment, categorizing nanosystems based on their organic (polymeric, lipidic, protein) or inorganic (metallic, silica‐based, metal–organic framework) composition. Design principles and therapeutic performances are discussed, and emerging directions for next‐generation nanomedicine are highlighted.
Plaza-Palomo et al. (Mon,) studied this question.