Immuno‐Polymeric Nanoparticles by Diels–Alder Chemistry

Doxorubicin‐Conjugated Immuno‐Nanoparticles for Intracellular Anticancer Drug Delivery

“…The furan-functionalized amphiphilic copolymer, poly(TMCC-co-LA)-g-PEG-furan, was synthesized as previously reported, [2] as was its ability to self-assemble into nanoparticle structures via a dialysis procedure. [2,12] As shown in Scheme 1, the hydrophobic segments of the poly(TMCC-co-LA) backbone form the dense inner core while the hydrophilic PEG chains orient toward the aqueous solution forming the outer corona upon self-assembly in aqueous environments.…”

“…[2,12] As shown in Scheme 1, the hydrophobic segments of the poly(TMCC-co-LA) backbone form the dense inner core while the hydrophilic PEG chains orient toward the aqueous solution forming the outer corona upon self-assembly in aqueous environments. The furan functional groups, located at the PEG termini, are easily accessible to maleimide-containing molecules in the aqueous solution.…”

“…We previously demonstrated that antibodies can be covalently bound on the surface of the polymeric nanoparticles via highly efficient Diels-Alder (DA) chemistry. [2] By calculating the aggregation number of the micellar nanoparticles, it was estimated that antibodies occupied only a few of the PEG-furan groups on the surface, leaving thousands of surface PEG-furan chains available for further modification. [2] In this study, we take advantage of the mild DA reaction conditions to couple DOX-maleimide to those unoccupied PEG-furan chains by the same DA chemistry, resulting in colabeled DOX-antibody-nanoparticles where both chemotherapeutics and targeting antibodies are on the outside of the nanoparticles (Scheme 1).…”

Microbubble Therapies

“…Cell targeting can be achieved with a series of complementary immunoliposome (Siwak et al, 2002) and nanoparticle ligands (Shi et al, 2007) to specific cell surface receptors attached to the microbubble shells. Isolated or preferential expression of particular diseased cell-specific receptors on their surface provides a means by which targeting discrimination can be achieved.…”

Biodegradable polycarbonate-based stimuli-responsive nanosystems for intracellular delivery

“…Shoichet's group described an elegant route to immuno-polymeric micelles based on P(TMCC-co-DLLA)-graft-furan-terminated PEG copolymer (P(TMCC-co-DLLA)-g-PEG-furan) via amido links through functional carboxyl groups on carbonate units [58]. Furan groups on the outer PEG shell of the micelles were then reacted with a maleimide-modified anti-HER2 (a therapeutic antibody used to treat breast cancer) by Diels-Alder cycloaddition.…”