Janus "nano-bullets" for magnetic targeting liver cancer chemotherapy.
Tumor-targeted delivery of anti-cancer drugs with controlled drug release function has been recognized as a promising strategy for pursuit of increased chemotherapeutic efficacy and reduced adverse effects. Development of magnetic nanoparticulates as delivery carriers to accommodate cytotoxic drugs for liver cancer treatment has evoked immense interest with respect to their convenience in biomedical application. Herein, we engineered multifunctional Janus nanocomposites, characterized by a head of magnetic Fe3O4 and a body of mesoporous SiO2 containing doxorubicin (DOX) as "nano-bullets" (M-MSNs-DOX). This nanodrug formulation possessed nanosize with controlled aspect-ratio, defined abundance in pore structures, and superior magnetic properties. M-MSN-DOX was determined to induce selective growth inhibition to the cancer cell under magnetic field rather than human normal cells due to its preferable endocytosis by the tumor cells and pH-promoted DOX release in the interior of cancer cells. Ultimately, both subcutaneous and orthotropic liver tumor models in mice have demonstrated that the proposed Janus nano-bullets imposed remarkable suppression of the tumor growth and significantly reduced systematic toxicity. Taken together, this study demonstrates an intriguing targeting strategy for liver cancer treatment based on a novel Janus nano-bullet, aiming for utilization of nanotechnology to obtain safe and efﬁcient treatment of liver cancer.
Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China; Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
Dan
D
Shao
Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
Jing
J
Li
Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
Xiao
X
Zheng
Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
Yue
Y
Pan
Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China.
Zheng
Z
Wang
Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
Ming
M
Zhang
CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China.
Qi-Xian
QX
Chen
CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China. Electronic address: wenfeidong@126.com.
Wen-Fei
WF
Dong
Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; School of Nursing, Jilin University, Changchun 130021, China. Electronic address: chenl@jlu.edu.cn.
Li
L
Chen
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008813:Mice, Inbred ICR; D053761:Nanocomposites / Q000737:chemistry; D058726:Nanoconjugates / Q000737:chemistry*; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*
D000903:Antibiotics, Antineoplastic; D058185:Magnetite Nanoparticles; D058726:Nanoconjugates; D012822:Silicon Dioxide; D004317:Doxorubicin
Chemotherapy; Janus; Liver cancer; Low systemic toxicity; Magnetic mesoporous silica; Magnetic targeting