Carrier-free nanoparticles for cancer therapy: assembly strategies, therapeutic applications, and clinical translation.
Carrier-free nanoparticles have emerged as a promising class of nanomedicines for cancer therapy, characterized by ultrahigh drug-loading capacity, reduced dependence on inert carriers, and enhanced therapeutic efficiency. Diverse design strategies, including molecular self-assembly, covalent prodrug conjugation, and stimuli-responsive construction, have enabled the development of structurally versatile and functionally integrated carrier-free nanoplatforms. These systems exhibit improved physicochemical properties, enhanced tumor accumulation, and multifunctional therapeutic capabilities. However, existing reviews have mainly focused on specific assembly strategies or individual therapeutic applications, while a systematic understanding linking nanoparticle design, tumor-specific responses, and clinical translation remains insufficient. This review summarizes recent advances in the design and fabrication of carrier-free nanoparticles and provides an integrated analysis of their assembly mechanisms, physicochemical characteristics, and therapeutic applications across diverse cancer types, including breast, lung, and liver cancers. In addition, this review comparatively discusses different therapeutic modalities, including chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, ferroptosis, and immunotherapy, with emphasis on their advantages, limitations, and translational potential. Current clinical progress, patent trends, and future challenges are also analyzed to provide insights into the rational design and clinical development of carrier-free nanoparticles for cancer therapy.