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 ef-ficacy 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.

Automated summary

This study presents a lipid-functionalized gold nanorods-based mitochondrial targeting photothermal-chemotherapy all-in-one nanoplatform, which can effectively improve the therapeutic effects of cancer. The constructed nanoplatform achieves mitochondrial targeting, photothermal therapy, and dual drug loading, efficiently generating reactive oxygen species in mitochondria and exhibiting excellent anti-tumor efficacy. This promising strategy provides a feasible approach for organelle-targeted combination photothermal-chemotherapy to enhance therapeutic effects.