Nanospheres of doxorubicin as cross-linkers for a supramolecular hydrogelation.
In this study, we synthesized a peptide of Nap-GFFYGRGD, which could self-assemble into supramolecular nanofibers. The peptide itself could only form nanofibers but not hydrogels due to the relative weak inter-fiber interactions. The resulting nanofibers were then utilized as the vehicles for anticancer drug doxorubicin. It was found that the nanofibers of Nap-GFFYGRGD could not encapsulate doxorubicin, whereas the drug formed nanospheres, which were located at the surface of the nanofibers. Due to the electrostatic interactions between the negatively charged nanofibers and the positively charged doxorubicin nanospheres, the doxorubicin nanospheres were able to serve as a cross-linker to increase the inter-fiber interactions, leading to the formation of stable three-dimentional fiber networks and hydrogels. The resulting doxorubicin-peptide hydrogels were capable of releasing the drug in a sustained manner, which also showed comparable cytotoxicity as compared to free doxorubicin against a variety of cancer cell lines including HeLa and MCF-7 cancer cells. Therefore, this successful example using drug as the peptide nanofiber cross-linkers provided a new strategy for fabricating supramolecular hydrogelation for controlled delivery of anticancer drugs.
National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. R. China.
Qiang
Q
Xue
National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. R. China.
He
H
Ren
National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. R. China.
Chao
C
Xu
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin. 300071, P. R. China.
Gang
G
Wang
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin. 300071, P. R. China.
Chunhua
C
Ren
National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. R. China.
Jihui
J
Hao
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin. 300071, P. R. China.
Dan
D
Ding
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000633:toxicity; D057139:Nanofibers / Q000737:chemistry / Q000648:ultrastructure; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry*
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D020100:Hydrogels; D010455:Peptides; D004317:Doxorubicin