Tumor-specific disintegratable nanohybrids containing ultrasmall inorganic nanoparticles: from design and improved properties to cancer applications

The size of nanoparticles is highly related to their intratumor penetration ability and long-time accumulation-derived toxicity to normal organs. The moderate particle size (50-200 nm) favors the intratumor accumulation, while both the deep penetration into tumors and the quick clearance from the body require particle size to be as small as possible (generally less than 10 nm). How to balance the contradiction regarding particle size is vitally important for enhancing cancer therapy efficacy and reducing toxicity, but is still challenging. One of the reasonable solutions is to design disintegratable nanohybrids, which are assembled into a desired size of bigger nanoparticles from ultrasmall particles and are also able to disassemble into ultrasmall particles in a responsive/controlled way. Tumor-specific disintegratable nanohybrids containing ultrasmall functional inorganic nanoparticles could achieve long blood circulation and extravasate after reaching the tumor site, and they could be triggered by stimuli to disintegrate into small particles in favor of their penetration into deep tumor tissue and their clearance by the body. Moreover, the integration of multiple functional nanoparticles into nanohybrids can significantly amplify their physicochemical performances, enhancing the efficacies for cancer diagnosis and treatment. Herein, this review summarizes the design strategies of tumor-specific disintegratable nanohybrids, indicates their improved properties, and highlights their applications in highly effective diagnosis and treatment of cancer.