Enhancement of cancer therapy efficacy by trastuzumab-conjugated and pH-sensitive nanocapsules with the simultaneous encapsulation of hydrophilic and hydrophobic compounds

Trastuzumab-conjugated pH-sensitive double emulsion nanocapsules (DENCs) stabilized by a single-component Poly (vinyl alcohol) (PVA) with magnetic nanoparticles can be fabricated through a two-step double emulsion process; these nanocapsules can be used to encapsulate hydrophilic doxorubicin (Dox) and hydrophobic paclitaxel (PTX) simultaneously. When PMASH was attached to the shell of the DENCs, enhanced dual drug release of PTX/Dox was detected, specifically in intracellular acidic pH environments. The targeting ability of these Trastuzumab-conjugated DENCs was demonstrated with confocal images, which revealed a significantly elevated cellular uptake in HER-2 overexpressing SkBr3 cells. More importantly, an intravenous injection of this co-delivery system followed by magnetic targeting (MT) chemotherapy suppressed cancer growth in vivo more efficiently than the delivery of either PTX or Dox alone. The integration of the functionalities makes this combination therapy system a powerfully new tool for in vitro/in vivo cancer therapy, especially for in HER-2 positive cancers.From the Clinical EditorTrastuzumab-conjugated pH-sensitive nanocapsules were used in this study for simultaneous targeted delivery of hydrophobic (PTX) and hydrophilic (Dox) anti-cancer agents to HER-2 positive cancer cells. Additional use of magnetic targeting demonstrated superior efficacy of this delivery system compared to PTX or Dox alone.

Graphical AbstractDouble emulsion nanocapsules (DENCs) which simultaneously encapsulated hydrophobic and hydrophilic drugs in reaching synergistic therapy were successfully synthesized. A dual targeting system for Trastuzumab modification and magnetic guidance was achieved which made the localization of DENCs to the targeting cells become available. Besides, pH-sensitivity of DENCs concealed the drugs in neutral environment but released them spontaneously in acidic intracellular compartments. Together with simultaneous delivering dual drugs, pH-sensitivity, and co-targeting effects, DENCs provides a novel therapy for HER-2 overexpressing breast cancer.Figure optionsDownload high-quality image (251 K)Download as PowerPoint slide