A Redox-Sensitive Micelle-Like Nanoparticle Self-Assembled from Amphiphilic Adriamycin-Human Serum Albumin Conjugates for Tumor Targeted Therapy

Abstract EN

The application of chemotherapeutic drug adriamycin (ADR) in cancer therapy is limited byits side effects like high toxicity and insolubility.

Nanomedicine offers new hope forovercoming the shortcomings.

But how to increase in vivo stability and to control intracellulardrug release is a key issue for nano-based formulations.

Herein, the hydrophobic ADR wassuccessfully linked to the biocompatible human serum albumin (HSA) by disulfide bond3-(2-pyridyldithio) propionyl hydrazide (PDPH), resulting in amphiphilic HSA-ADR.

Thenovel ADR-HSA micellar NPs which were thus assembled exhibited a well-defined stablecore shell structure with glutathione (GSH) sensitive linkers.

The stable PDPH linkers atextracellular level were broken by GSH at intracellular level with a controlled ADR releaseprofile.

The in vitro cytotoxicity against gastric cancer cells (NCI-N87) was obviouslyenhanced by such redox-sensitive ADR-HSA NPs.

Additionally, as observed by IVISLumina II Imaging System (Xenogen), the intratumor accumulation of ADR-HSA NPs wasmuch higher than that of HSA/ADR NPs due to its high stability.

Consequently, the in vivotumor inhibition was significantly promoted after intravenous administration to the Balb/c nude micebearing gastric tumors.

These in vitro/vivo results indicated that disulfide-bond-containingADR-HSA NPs were an effective nanodrug delivery system for cancer therapy.