Lipid-functionalized gold nanorods with plug-to-direct mitochondria targeting ligand for synergetic photothermal-chemotherapy of tumor therapy

Mitochondria targeting therapeutic strategies are promising for more effective and precise cancer therapy. Photothermal therapy are extensively studied as noninvasive cancer treatment. With regards to all-in-one nanocarrier-mediated drug delivery platform, it is still a challenge to enhance one of the features but not compromise other merits. Herein, we present a mitochondrial targeting photothermal-chemotherapy all-in-one nanoplatform involving lipid-functionalized gold nanorods (AuNR) with plug-to-direct mitochondria targeting ligand for synergetic enhanced tumor therapy. Firstly, AuNR were modified by DSPE-PEG-SH owing to the special affinity of sulfhydryl group and gold. And then, DSPE-PEG-DOX with mitochondrial targeting character was directly inserted into DSPE-PEG-SH layer. Meanwhile, paclitaxel (PTX) was loaded in hydrophobic region of the lipid layer. Quite different from introducing additional mitochondrial targeting molecules, we incorporated amphiphilic DSPE-PEG-DOX into a DSPE-PEG-SH layer modified around AuNR to achieve both mitochondrial targeting, photothermal and dual drug loading in a simple AuNR-lipid-DOX/PTX platform, in the case that efficiently enhanced production of reactive oxygen species (ROS) in mitochondria and excellent anti-tumor efficacy were achieved. With good biocompatibility, the constructed nanoplatform based on lipid-functionalized AuNR synergistically combined mitochondrial targeted DSPE-PEG-DOX with mitochondrial-acted PTX and photothermal therapy (PTT), which provided a feasible strategy for organelle-targeted combination PTT-chemotherapy to improve therapeutic effects.