Carrier-free self-assembled nanodrugs show broad application prospects in cancer treatment. Compared with carrier-based nanodrugs, carrier-free self-assembled nanodrugs have the advantages of strong targeting ability and high safety, which can significantly improve the therapeutic efficacy against cancer. Their preparation process is simple, involving a variety of non-covalent interactions, and they exhibit better biocompatibility and immune effects in vaccine development. Carrier-free self-assembled nanodrugs can be divided into nanodrugs based on prodrugs, free drugs, and amphiphilic drug conjugates. In this review, the preparation methods of these three types of carrier-free self-assembled nanodrugs and their research progress in cancer treatment in recent years were summarized, and their clinical applications and future prospects were discussed.

Pullulan, a natural polysaccharide, has good biocompatibility and biodegradability. Pullulan and its derivatives show broad application prospects in tumor-targeted delivery and therapy. In this review, various nano delivery systems based on pullulan and its derivatives were reviewed. Among them, pullulan-related nanogels, nanoparticles, and nanomicelles can enhance the targeting and penetration of chemotherapeutic drugs while reducing toxicity to normal tissues, pullulan-related gene nano delivery systems can show good performance and improve gene transfection efficiency, and pullulan-related bioresponsive nano delivery systems can further enhance therapeutic efficacy while avoiding multidrug resistance.