期刊
BIOMATERIALS
卷 199, 期 -, 页码 76-87出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.01.036
关键词
Functional polymers; Guanidinium-functionalized polycarbonate; Anticancer; Multidrug resistance; Tumor metastasis
资金
- Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore)
- Zhejiang Provincial Natural Science Foundation of China [LQ16H160012]
- National Natural Science Foundation of China [NSFC-81502618]
Although mortality continues to decline over the past two decades, cancer is still a pervasive healthcare problem worldwide due to the increase in the number of cases, multidrug resistance (MDR) and metastasis. As a consequence of multidrug resistance, cancer treatment must rely on a host of chemotherapeutic agents and chemosensitizers to achieve remission. To overcome these problems, a series of biodegradable triblock copolymers of PEG, guanidinium-functionalized polycarbonate and polylactide (PEG-PGCx(-)PDLA(y)) is designed as chemotherapeutic agents. These copolymers self-assemble into micellar nanoparticles, and are highly effective against various cancer cell lines including human breast cancer (BCap37), liver cancer (HepG2), lung cancer (A549) and epidermoid carcinoma (A431) cell lines as well as MDR Bats-72 and Bads-200 cancer cells that were developed from BCap37. Multiple treatments with the polymers at sub-lethal doses do not induce resistance. The polymers kill cancer cells by a non-apoptotic mechanism with significant vacuolization and subsequent membrane disruption. In vivo antitumor efficacy is evaluated in a metastatic 4T1 subcutaneous tumor model. Treatment with stereocomplexes of PEG-PGC(43)-PLLA(19) and PEG-PGC(43)-PDLA(20) at a dose of 20 mg/kg of mouse body weight suppresses tumor growth and inhibits tumor metastasis in vivo. These polymers show promise in the treatment of cancer without the onset of resistance.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据