Rattle-Structured Rough Nanocapsules with in-Situ-Formed Gold Nanorod Cores for Complementary Gene/Chemo/Photothermal Therapy.

The morphology of nanoparticles influences their cellular uptake process, while rough surface-enhanced affinity renders rough nanoparticles desirable in related biomedical applications. In this work, rattle-structured rough nanocapsules (Au@HSN-PGEA, AHPs) composed of in-situ-formed gold nanorod (Au NR) cores and polycationic mesoporous silica shells were constructed for trimodal complementary cancer therapy. Taking advantage of surface roughness, near-infrared (NIR) responsiveness, and controlled release manner, AHPs were expected to realize the co-delivery of sorafenib (SF, a hydrophobic antiproliferative and antiangiogenic drug) and antioncogene p53 for malignant hepatocellular carcinoma treatment. The rough surface feature of AHP was investigated for cellular uptake and the subsequent gene transfection. The feasibility of photothermal Au NR cores for NIR-triggered SF release was also tested. Notably, synergistic effects based on photothemal therapy-enhanced chemotherapy were achieved. In addition, the good in vivo performance of the proposed multifunctional nanoparticles with rough surfaces was also demonstrated. The current work extends the biomedical applications of the intriguing rough nanoparticles and provides a facile strategy to construct flexible platforms for complementary gene/chemo/photothermal therapy.