Magnetically Targeted Nanocapsules for PAA-Cisplatin-Conjugated Cores in PVA/SPIO Shells via Surfactant-Free Emulsion for Reduced Nephrotoxicity and Enhanced Lung Cancer Therapy

Chih Sheng Chiang, Yi Hsuan Tseng, Bang Jie Liao, San-Yuan Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Cis-diamminedichloroplatinum (II) (cisplatin, CDDP) is one of the most potent chemotherapy agents, but its side effects toward normal tissues, particularly toxicity in the kidney and nonspecific biodistribution, limit its ability to have significant clinical activity against a variety of solid tumors. A magnetic CDDP-encapsulated nanocapsule (CDDP-PAA-NC) with CDDP-polyacrylic acid (PAA) core in amphiphilic polyvinyl alcohol/superparamagnetic iron oxide nanoparticles shell is synthesized through a double emulsion to provide both high loading efficiency and controlled drug release. The CDDP-PAA-NCs significantly increase the blood circulation time of CDDP in vivo, with nearly 100-fold higher concentration, and drastically reduce side effects, including nephrotoxicity and hepatotoxicity, compared with the delivery of free CDDP. Furthermore, with a magnetic targeting effect, the CDDP-PAA-NCs show ninefold higher level accumulation in tumor tissue than the free CDDP treatment when administered at the equivalent dose, and mice treated with the CDDP-PAA-NCs display approximately 3.5-fold lower tumor volume than those of the control group on day 24. This result demonstrates that the magnetic CDDP-PAA-NCs, which are synthesized using a facile emulsion process, can significantly reduce toxicity and exhibit anticancer activity in A549-tumor bearing mice with negligible side effects. Magnetic cis-diamminedichloroplatinum-encapsulated nanocapsules (CDDP-PAA-NCs) are synthesized via surfactant-free emulsion to conceal the polyacrylic acid -CDDP complex in the core of polyvinyl alcohol/superparamagnetic iron oxide. The nanocapsules display high loading efficiency and significantly increase the blood circulation time of CDDP in vivo. With magnetic targeting, the CDDP-PAA-NCs can achieve efficacious therapy with negligible side effects.

Original languageEnglish
Pages (from-to)1066-1075
Number of pages10
JournalAdvanced Healthcare Materials
Volume4
Issue number7
DOIs
StatePublished - 1 May 2015

Keywords

  • Cisplatin
  • Magnetic targeting
  • Superparamagnetic nanoparticles
  • Tumor selectivity

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