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

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.