Biomimetic Phytic Acid–Metal–Albumin Nanocomplexes for Tumor-Selective, Bioclearable Theranostics
Dengyi Duan, Jing Peng, Wenyi Zhang, Jianmin Li, Kangkang Liu, Lin Cao, Shuang Liu, Yiming Li, Yuanjie Niu, Xiaomin Wang, Gang Han, Yang ZhaoAbstract
Conventional nanoparticles for tumor imaging and therapy often fail due to poor clearance, prolonged circulation, and toxic off-target effects. We introduce a biomimetic phytic acid (PA)–metal–albumin nanoternary complex that repurposes the body’s natural PA–metal–protein assembly/clearance axis to enable tumor-targeted theranostics. The platform is serum-stable, bioclearable, and supports a broad spectrum of imaging and therapeutic payloads. For example, PA chelates manganese (Mn2+) for high-contrast T1-weighted magnetic resonance imaging, platinum (Pt) for chemotherapy, and radium-223 (Ra-223) for alpha radiotherapy. In the acidic environment of tumor endosomes, the complexes undergo programmed aggregation to maximize intratumoral retention, while systemic elimination follows physiological detox pathways. Released Mn2+ enhances cGAS–STING immune activation, amplifying antitumor responses. This clearance-competent, biomimetic nanoplatform unifies imaging, therapy, and immune modulation, advancing precision oncology with strong translational potential.