Doxorubicin‐Conjugated Immuno‐Nanoparticles for Intracellular Anticancer Drug Delivery

Abstract

A polymeric nanoparticle comprised of surface furan groups is used to bind, by Diels–Alder (DA) coupling chemistry, both targeting anti‐human epidermal growth factor receptor 2 (anti‐HER2) antibodies and chemotherapeutic doxorubicin (DOX) for targeted, intracellular delivery of DOX. In this new approach for delivery, where both chemotherapeutic and targeting ligand are attached, for the first time, to the surface of the delivery vehicle, the nuclear localization of DOX in HER2‐overexpressing breast cancer SKBR‐3 cells is demonstrated, as determined by confocal laser scanning microscopy. Flow cytometric analysis shows that the conjugated DOX maintains its biological function and induces similar apoptotic progression in SKBR‐3 cells as free DOX. The viable cell counts of SKBR‐3 cancer cells following incubation with different nanoparticle formulations demonstrates that the combined DOX and anti‐HER2 nanoparticle is more efficacious than the nanoparticle formulation with either DOX or anti‐HER2 alone. While free DOX shows similar cytotoxicity against both cancerous SKBR‐3 cells and healthy HMEC‐1 cells, the combined DOX‐anti‐HER2 nanoparticle is significantly more cytotoxic against SKBR‐3 cells than HMEC‐1 cells, suggesting the benefit of nanoparticle‐conjugated DOX for cell type‐specific targeting. The DOX‐conjugated immuno‐nanoparticle represents an entirely new method for localized co‐delivery of chemotherapeutics and antibodies.

Click Chemistry for Drug Delivery Nanosystems

“…The anti-HER2 immunomicelles specifically bound to HER2-over-expressing cells, demonstrating the strength of this procedure to create bioactive immuno-micelles. As only a few anti-HER2 antibodies on the surface of micelles were necessary for targeting, thousands of PEG-furan chains were available for coupling to a DOX-maleimide conjugate in a subsequent step (50). Resulting DOX-conjugated immuno-micelles represent an entirely new method for localized codelivery of chemotherapeutics and antibodies.…”

Direct Synthesis of Biodegradable Polysaccharide Derivative Hydrogels Through Aqueous Diels‐Alder Chemistry

“…[36][37] 0.5 g HA sodium (MW %1.6 Â 10 6 ) was dissolved in 100 ml nanopure H 2 O and activated by N-ethyl-N 0 -(3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysulfosuccinimide (EDAC/Sulfo-NHS). 0.5 g Furan-PEG-NH 2 was dissolved in a borate buffer solution (500 mM, pH 9.0) and then slowly added to the activated HA sodium solution under stirring.…”

Temperature-Tunable Iron Oxide Nanoparticles for Remote-Controlled Drug Release

“…The intracellular localization of DOX plays an important role in its anticancer activity (34,35). Therefore, localization of DOX in the multidrug-resistant A2780/AD ovarian carcinoma cells after incubation with drug loaded into IONPs-PNAP was evaluated by fluorescence microscopy employing intrinsic fluorescence properties of DOX.…”