Lanthanide-integrated supramolecular polymeric nanoassembly with multiple regulation characteristics for multidrug-resistant cancer therapy

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

20 Scopus Citations
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Author(s)

  • Weihong Jin
  • Qiwen Wang
  • Min Wu
  • Yang Li
  • Guping Tang
  • Yuan Ping

Detail(s)

Original languageEnglish
Pages (from-to)83-97
Journal / PublicationBiomaterials
Volume129
Publication statusPublished - 1 Jun 2017

Abstract

Cancer treatment can in principle be enhanced by the synergistic effects of chemo- and nucleic acid-based combination therapies but the lack of efficient drug nanocarriers and occurrence of multidrug resistance (MDR) are major obstacles adversely affecting the effectiveness. Herein, a lanthanide-integrated supramolecular polymeric nanoassembly that delivers anticancer drugs and siRNA for more effective cancer therapy is described. This nanotherapeutic system is prepared by loading adamantane-modified doxorubicin (Dox) into polyethylenimine-crosslinked-γ-cyclodextrin (PC) through the supramolecular assembly to form the interior Dox-loaded PC (PCD) followed by electrostatically driven self-assembly of siRNA and PCD to produce the PCD/siRNA nanocomplexes. The PCD/siRNA nanocomplex is further decorated with the exterior neodymium (Nd)-integrated PC (Nd-PC) layer to obtain the PCD/siRNA/Nd-PC nanoassembly in which the interior PC serves as an efficient carrier for simultaneous delivery of Dox and siRNA to the human breast cancer cell line, Dox-resistant MCF-7 (MCF-7/ADR) both in vitro and in vivo. The exterior Nd-PC layer improves the drug sensitivity to the MCF-7/ADR cells as a result of the improved nanoassembly uptake, reduced drug efflux, and enhanced apoptosis, as evidenced by multiple regulation of a series of intracellular proteins related to MDR. Furthermore, in vivo delivery of the PCD/siRNA/Nd-PC nanoassembly is demonstrated to inhibit tumor growth in the mouse model with MCF-7/ADR tumor xenografts as a result of reduced angiogenesis and increased necrosis at the tumor site. This study reveals a simple and universal strategy to transform polymer-based nanoassemblies into advanced organic-inorganic nanotherapeutics suitable for cancer MDR therapy.

Research Area(s)

  • Chemotherapy, Drug delivery, Nanomedicine, Organic-inorganic hybrid materials, siRNA

Citation Format(s)

Lanthanide-integrated supramolecular polymeric nanoassembly with multiple regulation characteristics for multidrug-resistant cancer therapy. / Jin, Weihong; Wang, Qiwen; Wu, Min; Li, Yang; Tang, Guping; Ping, Yuan; Chu, Paul K.

In: Biomaterials, Vol. 129, 01.06.2017, p. 83-97.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal