Fabricating an intelligent cell-like nano-prodrug via hierarchical self-assembly based on the DNA skeleton for suppressing lung metastasis of breast cancer

• Published in: Biomaterials science 2019-08, Vol.7 (9), p.3652-3661
• Main Authors: Li, Yunyan, Yan, Tong, Chang, Wenya, Cao, Chongjiang, Deng, Dawei
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - chemical synthesis; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Biocompatibility; Biomimetics; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemical compounds; Deoxyribonucleic acid; DNA; DNA, Neoplasm - drug effects; Dose-Response Relationship, Drug; Doxorubicin - administration & dosage; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Screening Assays, Antitumor; Drugs; Female; Homing; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Metastasis; Molecular Structure; Nanomaterials; Nanoparticles - chemistry; Optical Imaging; Particle Size; Prodrugs - administration & dosage; Prodrugs - chemical synthesis; Prodrugs - chemistry; Prodrugs - pharmacology; Self-assembly; Structure-Activity Relationship; Surface Properties; Tetrahedra; Therapy
• ISSN: 2047-4830; 2047-4849
• DOI: 10.1039/c9bm00630c

Cancer metastasis is a major cause of high mortality in breast cancer. Despite the progress achieved in nanomaterial-based treatments, the cure rate remains unsatisfactory, owing to their poor biocompatibility and non-specific recognition. Inspired by the cell-mimetic strategy, in this work, we fabricated an intelligent cell-like nano-prodrug (Dox-MPK@MDL) for lung metastasis of breast cancer. Specifically, a DNA tetrahedron dendrimer was selected to act as a rigid internal cytoskeleton, and then sequentially coated with a liposome and macrophage membrane to form cell-like Dox-MPK@MDL via hierarchical self-assembly. Here, it should be noted that pH-sensitive Dox-MPK prodrugs were synthesized and inserted into the DNA-based cytoskeleton (the Dox group is an intercalator of double stranded DNA) in advance for the next anti-metastatic therapy. Our results show that Dox-MPK@MDL specifically targeted the sites of lung metastasis via the biomimetic metastasis-homing effects and intelligently triggered Dox release at the metastatic cancer cells, thereby leading to the significant inhibition of lung metastasis. All these features help to enhance the anti-metastatic therapy efficiency of Dox while maximally reducing side-effects.