The treatment of liver cancer remains challenging due to the low responsiveness of advanced cancer to therapeutic options. Sorafenib is the first line chemotherapeutic drug for advanced liver cancer but is frequently associated with severe side effects lead to discontinuation of chemotherapy. We previously developed a specific SIRT7 inhibitor 2800Z, which suppressed tumor growth and enhanced the chemosensitivity of sorafenib. In this study, we constructed polylysine polymer nanoparticles modified with cholesterol and GSH-sensitive PEG (mPssPC) to load sorafenib (SOR) and the SIRT7 inhibitor 2800Z to form dual-loaded NPs (S2@PsPCs) to reduce the toxicity and increase efficacy of sorafenib in liver cancer. The average size of S2@PsPC NPs was approximately 370 nm and the zeta potential was approximately 50–53 mV. We found that the release of the drugs exhibited pH sensitivity and was significantly accelerated in an acid release medium simulating the tumor environment. In addition, S2@PsPC NPs inhibited the proliferation and induced apoptosis of liver cancer cells in vitro. An in vivo study further revealed that S2@PsPCs showed high specificity to the liver cancer but low affinity and toxicity to the main organs including the heart, kidneys, lungs, and liver. Our data thus further approved the combination of a SIRT7 inhibitor and sorafenib for the treatment of liver cancer and provided new drug delivery system for targeted therapy.

Triple negative breast cancer (TNBC), which has poor prognosis, easily develops drug resistance and metastasizes. In general, those TNBC characteristics are related to a high activation of the epithelial-mesenchymal transition (EMT) pathway, which is inhibited by shikonin (SKN). Therefore, the synergistic therapy of SKN and doxorubicin (DOX) will increase anti-tumor efficacy and reduce metastasis. In this study, we prepared the folic acid-linked PEG nanomicelle (NM) grafted with the DOX (denoted as FPD) to load the SKN. We prepared the SKN@FPD NM according to the effective ratio of dual drugs, where the drug loadings of DOX and SKN were 8.86 ± 0.21% and 9.43 ± 0.13%, with 121.8 ± 1.1 nm of its hydrodynamic dimension and 6.33 ± 0.16 mV of zeta potential, respectively. The nanomaterials significantly slowed down the release of DOX and SKN over 48 h, leading to the release of pH-responsive drugs. Meanwhile, the prepared NM inhibited the activity of MBA-MD-231 cells in vitro. Further in vitro study revealed that the SKN@FPD NM increased the DOX uptake and significantly reduced the metastasis of MBA-MD-231 cells. Overall, these active-targeting NMs improved the tumor-targeting of small molecular drugs and effectively treated TNBC.