A Proof‐of‐Concept Study on the Theranostic Potential of 177Lu‐labeled Biocompatible Covalent Polymer Nanoparticles for Cancer Targeted Radionuclide Therapy.

Theranostic nanomedicine combined bioimaging and therapy probably rises more helpful and interesting opportunities for personalized medicine. In this work, 177Lu radiolabeling and surface PEGylation of biocompatible covalent polymer nanoparticles (CPNs) have generated a new theranostic nanoformulation (177Lu‐DOTA‐PEG‐CPNs) for targeted diagnosis and treatment of breast cancer. The in vitro anticancer investigations demonstrate that 177Lu‐DOTA‐PEG‐CPNs possess excellent bonding capacity with breast cancer cells (4T1), inhibiting the cell viability, leading to cell apoptosis, arresting the cell cycle, and upregulating the reactive oxygen species (ROS), which can be attributed to the good targeting ability of the nanocarrier and the strong relative biological effect of the radionuclide labelled compound. Single photon emission computed tomography/ computed tomography (SPECT/CT) imaging and in vivo biodistribution based on 177Lu‐DOTA‐PEG‐CPNs reveal that notable radioactivity accumulation at tumor site in murine 4T1 models with both intravenous and intratumoral administration of the prepared radiotracer. Significant tumor inhibition has been observed in mice treated with 177Lu‐DOTA‐PEG‐CPNs, of which the median survival was highly extended. More strikingly, 50 % of mice intratumorally injected with 177Lu‐DOTA‐PEG‐CPNs was cured and showed no tumor recurrence within 90 days. The outcome of this work can provide new hints for traditional nanomedicines and promote clinical translation of 177Lu radiolabeled compounds efficiently. [ABSTRACT FROM AUTHOR]