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

Abstract

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.

Branched-Chain-Induced Host–Guest Assembly in Covalent-Organic Frameworks for Efficient Separation of No-Carrier-Added 177Lu

“…177 Lu ( T 1/2 = 6.64 d) is one of the most clinically valuable radionuclides in anticancer investigation and practice. − Its +3 oxidation state is available for the efficient radiolabeling of various cancer-targeting bioactive vectors via common bifunctional chelators . Suitable half-life benefits multistep radiolabeling chemistry, drug transportation/storage, and long-distance delivery of related radiopharmaceuticals but short enough for the safety of nontargeted organs/tissues from high doses.…”

Preparation of Porphyrin-Based Unimolecular Micelles for Synergistic Photodynamic Therapy and Radiotherapy

“…This issue is often addressed by developing a variety of nanocarriers to deliver radionuclides to tumors through passive infiltration or active targeting to minimize side effects. 23 Polymeric carriers including micelles 24,25 have been widely used in biomedical fields because of their strong structural tunability, excellent biocompatibility, and long-term blood circulation, which often proximately determines the in vivo behavior of the drug and is crucial in practical application. 26−28 Compared to linear counterparts, amphiphilic polymers with specific topology such as star-shaped 29−31 and hyperbranched 32,33 exhibit unique aggregation behavior in water, namely, assembly as multimolecular joined micelles at high concentrations while unimolecular micelles (UIMs) 34−36 at low concentrations, and the concentration threshold at which the aggregation behavior varies is called the critical aggregation concentration (CAC).…”