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Cross-linking Poly(caprolactone)–Polyamidoamine Linear Dendritic Block Copolymers for Theranostic Nanomedicine

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journal contribution
posted on 06.01.2022, 20:44 by Indika Chandrasiri, Mahesh Loku Yaddehige, Bo Li, Yuzhe Sun, William E. Meador, Austin Dorris, Mohammad Farid Zia, Nathan I. Hammer, Alex Flynt, Jared H. Delcamp, Edward Davis, Alexander Lippert, Davita L. Watkins
This study represents a comparative analysis of the solution behavior and self-assembly pattern of two linear dendritic block copolymers (LDBCs) composed of a generation 3 polyamidoamine (PAMAM) dendron as the dendritic block and poly­(caprolactone) (PCL) as the linear block, the latter of which is modified with pendant phenyl groups. Phenyl substituents were introduced to induce physical cross-linking in LDBC nanoparticles via π–π stacking. A synthetic strategy was developed to access phenyl substituted LDBCs through an ε-caprolactone monomer derivative followed by ring-opening polymerization to form a library of LDBCs with yields above 83%. Polymersome-like nanoparticles were observed in water with a 74.4 nm average diameter. Cross-linked LDBC nanoparticles demonstrated a 37.1% relative decrease in the critical aggregation concentration (CAC) and a 27.3–41.2% relative increase of hydrophobic loading efficiency relative to unsubstituted LDBCs. Nanoparticles loaded with a potential photothermal agent (phenyl indolizine-C5 (C5)) showed a photothermal efficiency of 49.4% with a heating temperature of 44.4 °C. These nanoparticles were efficiently loaded into HEK293 cells with cell viability above 87.5% at the highest concentration. Upon illumination with red light, nanoparticles loaded with photothermal agent were able to induce cell death in cancer cells. This work suggests that the phenyl substituted LDBCs form nanoparticles with enhanced stability and loading efficiencies compared to conventional nonphenylated systems and display a greater potential to be used as nanocarriers in theranostic nanomedicine.