Engineering of Yin Yang-like nanocarriers for varisized guest delivery and synergistic eradication of patient-derived hepatocellular carcinoma

During the different clinical manifestations and periods in the treatment of hepatocellular carcinoma (HCC), the species and doses of drugs could be optimized to realize personalized therapy for an individual patient. Here, we firstly reported Yin Yang-like ultrasmall nanoparticles-stacked oleic acid–NaYF4:Yb,Er@hollow porous SiO2 nanoparticles (Yin Yang-like OA–UCNPs@HPS NPs) with a hydrophobic eccentric hollow structure and hydrophilic exterior surface possessing a wide pore size distribution via a novel method. The obtained NPs achieved the loading of multiple varisized hydrophobic/hydrophilic guests into the discrete rooms and the release of each one from the independent channels to reduce the undesirable adverse effects of different guests, which greatly favors the selection of drugs for an individual patient and enhances synergistic theranostics. The in vitro and in vivo (cell line-derived xenograft and patient-derived xenograft models) results demonstrated that the HCPT/DOX-loaded NPs could act as excellent theranostics agents for multimodal imaging-guided synergic dual-drug cancer therapy of HCC. Meanwhile, the potential mechanisms of action of the HCPT/DOX-loaded NPs after endocytosis by HCC cells were evaluated. The nanocomposite could further motivate the progress of new architectures of nanocarriers for varisized guest delivery and personalized treatment.