Polyamidoamine dendrimers of the third generation–chlorin e6 nanoconjugates: Nontoxic hybrid polymers with photodynamic activity

Dendrimer-based nanoconjugates play a key role as functional polymers for biomedical applications. In this work, the one-pot conjugation of polyamidoamine dendrimers of the third generation (PAMAM-G3) with the photosensitizer chlorin e6 (Ce6) is presented using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) to mediate the synthesis, resulting in a 9% substitution degree according to nuclear magnetic resonance data. The PAMAM-G3-Ce6 nanoconjugate exhibits reduced cytotoxicity compared with the native dendrimer and efficient photodynamic activity against HeLa cancer cells after 1 h of incubation with a 100 μmol L⁻¹ solution and 3 min of irradiation with red light-emitting diode light (628 nm, 259 W m⁻²). Molecular dynamics simulations confirm that the PAMAM-G3-Ce6 system adopts a spherical structure and retains the internal dendritic cavities that enable drug encapsulation, which is relevant for the potential use of these hybrid polymers in combined chemo/photodynamic therapy.