Cancer is a leading cause of death with rates expected to grow with life expectancy. Among leading treatments, cisplatin, widely used to combat cancer, suffers from low stability and selectivity. Here, we covalently conjugated an analog of cisplatin to biocompatible polydopamine nanoparticles (PDA-NPs) to increase both properties. Dynamic light scattering and electron microscopy studies suggest that the platinum-conjugated PDA particles (Pt-PDA-NPs) are monodispersed and spherical with a diameter of about 200 nm with platinum atoms mostly in the shell. Particles were also characterized with inductively coupled plasma mass atomic emission spectroscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy to determine the localization and amount of Pt atoms. The chelated metal did not leach from the conjugated particles under normal physiological conditions, while it was released only under acidic and oxidative conditions existing predominantly inside lysosomes and near cancer cells, suggesting their dual-stimuli responsiveness. Fluorescent microscopy confirmed that Pt-PDA-NPs are localized in the endoplasmic reticulum and internalized into cancer cells by endosomes. In cell survival experiments, particles are more toxic to human MCF-7 breast cancer cells compared to healthy NIH-3T3 cells. Mechanistic studies confirmed that the anticancer activity was induced by increased apoptosis. Field-dependent magnetization measurements suggest that Pt-PDA-NPs with a Gd3+-modified surface are paramagnetic and detectable by MRI, suggesting their promising theranostic application in cancer treatment.
Bibliographical noteFunding Information:
This research was supported by the Israel Innovation Authority (Grant 53876).
- cisplatin analogs
- dual stimuli responsive particles
- magnetic resonance imaging (MRI)
- polydopamine nanoparticles