Paclitaxel-loaded magnetic nanocrystals for tumor neovascular-targeted theranostics: an amplifying synergistic therapy combining magnetic hyperthermia with chemotherapy

A combination of chemotherapy and targeted magnetic hyperthermia (TMH) via a designed magnetic nanocrystal (MNC) drug delivery system was considered as an effective tumor synergistic therapy strategy. In this paper, we successfully synthesized tumor neovascular-targeted Mn-Zn ferrite MNCs, which encapsulated paclitaxel (PTX) in a biocompatible PEG-phospholipid (DSPE-PEG2000) layer and surface, simultaneously coupled with a tripeptide of arginine-glycine-aspartic acid (RGD). The high-performance RGD-modified MNC loaded with PTX (MNCs-PTX@RGD) embodied excellent magnetic properties, including high-contrast magnetic resonance imaging (MRI) and remarkable magnetically induced heat generation ability. We established the mouse model bearing subcutaneous 4T1 breast tumor, and demonstrated that MNCs-PTX@RGD could be effectively located in the tumor neovascular epithelial cells under the guidance of in vivo MRI. Notably, MNCs-PTX@RGD could easily penetrate into the tumor tissue from the tumor-fenestrated vascular networks for capturing a sufficient temperature (around 43 degrees C) exposed to an alternative current magnetic field (ACMF, 2.58 kA m(-1), 390 kHz), leading to an effective TMH effect. Subsequently, the TMH-mediated temperature elevation accelerated the PTX release from the inner lipid layer, promoting the synergetic thermo-chemotherapy in vivo. The amplifying synergistic treatment strategy obviously improved the anti-tumor efficacy of MNCs-PTX@RGD, and simultaneously increased the survival time of the mice to more than 46 days, which provided a broad development prospect in clinical applications.

Automated summary

This study successfully synthesized tumor neovascular-targeted Mn-Zn ferrite magnetic nanocrystals loaded with paclitaxel for effective tumor treatment through the combination of magnetic hyperthermia and chemotherapy. In vivo experiments demonstrated the excellent targeting and heating properties of this therapy, improving anti-tumor efficacy and increasing survival time in mice.