Silica–Polymer Hybrid with Self‐Assembled PEG Corona Excreted Rapidly via a Hepatobiliary Route

Nanotechnology‐based diagnostics and therapeutics usually suffer from long‐term retention of nanosized devices in the major organs, which may cause unwanted side effects. Herein, we describe the development of ultra‐small silica‐polymer hybrid dots (Sdots) through the self‐assembly between a polyethylene oxide‐poly(propylene oxide)‐polyethylene oxide (PEO‐PPO‐PEO) triblock copolymer and a silica precursor. Sdots feature a silica particle size of 4.2 nm and a hydrated size of 14 nm. The larger hydrated size is related to their polyethylene glycol (PEG) surface ligands, which evolve from the PEO blocks in the copolymer. The densely packed PEG corona can effectively shield the hybrid from reticuloendothelial uptake, which gives rise to rapid and thorough hepatobiliary clearance. In vivo experiments demonstrated that, upon intravenous injection, almost complete clearance of Sdots from mouse bodies could be realized through hepatobiliary excretion within only 5 days. Compared to renal clearable nanoparticles with short blood‐circulation times, the proposed Sdots have a prolonged blood‐circulation half‐life of 19 h, so that the Sdots could effectively accumulate at a subcutaneous transplanted tumor through enhanced penetration and retention. As the PPO core of the Sdots can be utilized to accommodate hydrophobic guest molecules, such as anticancer drugs, these Sdots can prospectively serve as fast‐clearable drug carriers for targeted cancer treatment.