Low density lipoprotein-inspired nanostructured lipid nanoparticles containing pro-doxorubicin to enhance tumor-targeted therapeutic efficiency.

Inefficient tumor accumulation and controlling drug release at the tumor site are two major obstacles limiting the antitumor efficacy of nanoparticle delivery systems. Inspired by the biological structure and function of low-density lipoprotein (LDL), a pH-sensitive ApoB-100/Oleic acid-DOX/NLC (AODN) nanoparticle based on nanostructured lipid carrier (NLC) was prepared in this study. The biological composition of ApoB-containing NLC nanoparticles is similar to that of LDL, which can effectively increase the cycle time and targeting efficiency of nanoparticles. Meantime, the doxorubicin prodrug strategy was used to increase the drug loading of the nanoparticles and achieve drug-sensitive release. In vitro results indicated that AODN nanoparticles can cause more drugs to be phagocytosed by LDL receptor-mediated endocytosis, thus showing high cytotoxicity in 4T1 cells. In vivo experiments have shown that pH-sensitive AODN nanoparticles can cause more drugs to accumulate in the tumor site, reducing systemic toxicity and effectively inhibiting orthotopic breast cancer. These data provide strong evidence that the strategy of combining bionics and prodrug technology provides a new approach to improving the efficiency of chemotherapy drugs in cancer treatment. STATEMENT OF SIGNIFICANCE: Inefficient tumor accumulation and controlling drug release at the tumor site are two major obstacles limiting the antitumor efficacy of nanoparticle delivery systems. Inspired by low density lipoprotein, a pH-sensitive ApoB-100/oleic acid-DOX/NLC (AODN) nanoparticle based on nanostructured lipid carrier (NLC) was prepared. Its biological composition is similar to that of LDL, which can effectively increase the cycle time and targeting efficiency of drugs. Then, the doxorubicin prodrug strategy was used to increase the drug loading of the nanoparticles and achieve drug-sensitive release. AODN nanoparticles can effectively inhibit tumor by effectively accumulating at tumor site and controlling release. The strategy of combining bionics and prodrug technology provides a new approach to improving the efficiency of chemotherapy drugs in cancer treatment.