Modular and efficient synthesis of a poly (propylene imine) (PPI) dendron applied to acid-sensitive doxorubicin conjugation

Targeted Doxorubicin-Loaded Dendronized Gold Nanoparticles

“…Starting from TA-TEG-G2NH 2 , a custommade azide-PEG 3 Michael acceptor was reacted to give the corresponding PPI-N 3 dendron 2 with a 65% yield. The PPI-DOX conjugate 3 (Figure 1), bearing three DOX molecules per PPI dendron, was synthesized as described in a previous publication [37]. and 48 h. The DOX release trend observed was similar to the release directly measured from the AuNP-DOX solution (see the previous paragraph).…”

“…Starting from TA-TEG-G2NH 2 , a custom-made azide-PEG 3 Michael acceptor was reacted to give the corresponding PPI-N 3 dendron 2 with a 65% yield. The PPI-DOX conjugate 3 ( Figure 1 ), bearing three DOX molecules per PPI dendron, was synthesized as described in a previous publication [ 37 ].…”

“…This value increased to λ SPR = 528 nm for AuNP-DOX/N 3 and further increased to λ SPR = 533 nm for AuNP-DOX/Fab ( Figure 4 B). The broadening of the SPR peak after the addition of DOX is most likely due to the absorption of PPI-DOX ( Figure S2 ) that occurs at a similar wavelength to AuNP but with a much broader peak (from 440 to 600 nm, with a λ max at around 505 nm) [ 37 , 48 ]. The addition of Fab fragments accentuates this broadening, because these 50 kDa proteins are significantly changing the environment of the AuNP core.…”

“…Starting from TA-TEG-G2NH2, a custom-made azide-PEG3 Michael acceptor was reacted to give the corresponding PPI-N3 dendron 2 with a 65% yield. The PPI-DOX conjugate 3 (Figure 1), bearing three DOX molecules per PPI dendron, was synthesized as described in a previous publication [37]. As a first attempt to prepare dendronized AuNP-Fab bioconjugates, PPI dendrons 1 and 2 were directly added to a basic solution of AuNP-citrate, as we reported previously, for the preparation of AuNP-CO 2 H [21].…”

“…These dendronized AuNPs had robust aqueous and serum stability, could withstand several rounds of lyophilization, and showed very low in vitro cytotoxicity. We have also shown that the PPI dendron could be conjugated to doxorubicin (DOX) as a model chemotherapeutic via an acid-labile hydrazone bond at a ratio of three DOX/dendron, giving PPI-DOX [ 37 ].…”