Title
Nano-rods of doxorubicin with poly(L-glutamic acid) as a carrier-free formulation for intratumoral cancer treatment
Author
Saina Yang, Feiyan Zhu, Qian Wang, Fuxin Liang, Xiaozhong Qu, Zhihua Gan, Zhenzhong Yang
Year
2016
Journal
Journal of Materials Chemistry B
Abstract
In addition to intravenous injections (i.v.), topical dosing of doxorubicin hydrochloride (DOX) has also been the focus of cancer treatment recently, although it normally requires well-designed drug carriers. In this work, we found that DOX could form fibril-shaped DOX aggregates via self-assembly in phosphate buffer (PB) and then co-assemble with poly(L-glutamic acid) (PGA) at a proper polymer–drug ratio, giving a unique nano-rod-shaped microstructure. The release rate of DOX from the PGA/DOX nano-rods was thus easily controlled at a slower release rate without being encapsulated by any classic carrier. In vitro cell culture demonstrated that the PGA/DOX nano-rods were not favorably taken up by cancer cells, which can be attributed to the negatively charged nature and the non-spherical shape of the aggregates. These features suggest great potential for the PGA/DOX assemblies for a sustained delivery through the intratumoral pathway (i.t.) as a carrier-free formulation. In the mouse model it diminished organ damage at a dose level of 30 mg kg−1 via i.t. injections compared to the serious cardiotoxicity and renal toxicity viatypical multiple i.v. dosage of free drug solution at 5 mg kg−1. As a result, the PGA/DOX formulation showed efficient anti-tumor activity. The survival rate of tumor bearing mice was significantly increased by over 35% compared to the i.v. injections of DOX solutions. Therefore, PGA/DOX nano-rods may provide a new and safe delivery route of the common anti-tumor drug.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Chemical stability, Nanostructures, Materials, Biochemistry