Breast cancer remains a major threat to women's health, and the incidence of breast cancer continues to increase each year. Paclitaxel (PTX) is commonly used to treat breast cancer, but shows limited solubility and is associated with major side effects, limiting its clinical applications. Photodynamic therapy (PDT) is a promising treatment for breast cancer but is limited by the poor solubility of photosensitizers and difficulties in targeting and enriching the tumor tissue with photosensitizers. Here, we prepared a new nanocarrier system using nanostructured lipid carriers (PTX@FA-NLC-PEG-Ce6) harboring PTX, chlorin e6 (Ce6), and folic acid-targeted head to overcome the limitations of PTX and Ce6 in hydrophobicity and increase the target efficiency of chemotherapy drugs and photosensitizers at the tumor. The results showed that the drug-loading system met the requirements for intravenous injection, had tumor targeting ability, and could be easily taken up by MDA-MB-231 cells. Moreover, Ce6 could be dissociated from the surface of the drug-loading system and evenly distributed in cells after a period of time when the nanostructured lipid carriers had entered lysosomes through endocytosis. Additionally, reactive oxygen species were then produced to induce PDT at a specific wavelength of illumination. In vitro pharmacodynamic experiments showed that combined PDT and chemotherapy had synergistic effects (combination index: 0.647). Furthermore, pharmacodynamic experiments in nude mice showed that the drug-loading system had ideal antitumor effects without obvious side effects. Thus, PTX@FA-NLC-PEG-Ce6 may have applications as a promising drug-loading system for PDT combined with chemotherapy in patients with breast cancer.

In this work, paclitaxel (Ptx) combined with tanshinone IIA (TanIIA) was found to show synergistic effect on inducing apoptosis of human acute promyelocytic leukemia (APL) cell line NB4, and the anti-tumor effect was strongest when its molar ratio was 1:1. To enhance the efficacy and reduce side effects, an active targeting drug delivery system with mesoporous silica nanoparticles (MSNs) coated with folic acid (FA) modified PEGylated lipid-bilayer (LB) membrane (FA-LB-MSNs) was established for co-loading drugs. The drug loadings of Ptx and TanIIA in FA-LB-MSNs were 5.5% and 1.8%, respectively. Compared with the uncoated MSNs, the FA-LB-MSNs showed a sustained drug release, and Ptx and TanIIA released synchronously from the carriers. By means of biological adhesion between FA and its receptors, the uptake of FA-LB-MSNs by NB4 cells was significantly higher than that of uncoated preparations, and Ptx combined with TanIIA had strong synergistic effect to enhance the apoptosis and differentiation of NB4 cells. The results of pharmacodynamics in vivo showed that the FA-LB-MSNs targeted tumor in nude mice more effectively than the compared formulations without FA modification. The Ptx and TanIIA-loaded FA-LB-MSNs group showed significantly better effects on inducing apoptosis and inhibiting tumor growth than the reference groups, which agreed with the results of anti-tumor experiments in vitro. Furthermore, no toxicity was observed to the heart, liver, spleen, lung and kidney of the tumor-bearing animals, indicating good biocompatibility of the prepared novel nanocarriers. This study confirmed the synergistic therapeutic effect of Ptx and TanIIA on APL, and the superior of FA-LB-MSNs as co-loaded nanocarriers for active targeted therapy of tumors.