Preclinical Development – Biomolecular
2019 PharmSci 360
Nature has inspired the advance in bio-derived structures attempting to act on the complex biological systems in a natural manner. Native high density lipoprotein (nHDL) is one of noteworthy platform candidates with highly adaptable nanostructure and tumor-homing capacity. Herein, we proposed nHDL based nanodrug for tumor site-specific dissociation and strengthened chemo-immunotherapy. The CpG oligodeoxynucleotides (CpG ODN) was conjugated with lipid to facilitate nHDL-surface decoration; then doxorubicin (Dox) was inserted into CpG ODN, completing decorated nHDL dHDL/CpG-Dox. After intravenously administration, dHDL/CpG-Dox collapsed in the tumor extracellular resulted from the interaction between apolipoproteins and HDL-receptor. Subsequently, Dox released from CpG-Dox and generated potent immunogenic cell apoptosis, while the liberated CpG ODN recruited and activated infiltrated M1 macrophages, cytotoxic T lymphocytes and natural killer cells for orchestration of immune cascade. Our study suggested that simultaneous influencing tumor cells and infiltrated immune cells mediated by dHDL/CpG-Dox could be an efficient method for cancer treatment.