Targeted Intraceptor Nanoparticle Therapy Reduces Angiogenesis and Fibrosis in Primate and Murine Macular Degeneration
详细信息 查看全文
- 作者：Ling Luo ; Xiaohui Zhang ; Yoshio Hirano ; Puneet Tyagi ; P茅ter Barab谩s ; Hironori Uehara ; Tadashi R. Miya ; Nirbhai Singh ; Bonnie Archer ; Yureeda Qazi ; Kyle Jackman ; Subrata K. Das ; Thomas Olsen ; Srinivas R. Chennamaneni ; Brian C. Stagg ; Faisal Ahmed ; Lyska Emerson ; Kristen Zygmunt ; Ross Whitaker ; Christina Mamalis ; Wei Huang ; Guangping Gao ; Sangly P. Srinivas ; David Krizaj ; Judit Baffi ; Jayakrishna Ambati ; Uday B. Kompella ; Balamurali K. Ambati
- 刊名：ACS Nano
- 出版年：2013
- 出版时间：April 23, 2013
- 年：2013
- 卷：7
- 期：4
- 页码：3264-3275
- 全文大小：880K
- 年卷期：v.7,no.4(April 23, 2013)
- ISSN：1936-086X
文摘
Monthly intraocular injections are widely used to deliver protein-based drugs that cannot cross the blood-retina barrier for the treatment of leading blinding diseases such as age-related macular degeneration (AMD). This invasive treatment carries significant risks, including bleeding, pain, infection, and retinal detachment. Further, current therapies are associated with a rate of retinal fibrosis and geographic atrophy significantly higher than that which occurs in the described natural history of AMD. A novel therapeutic strategy which improves outcomes in a less invasive manner, reduces risk, and provides long-term inhibition of angiogenesis and fibrosis is a felt medical need. Here we show that a single intravenous injection of targeted, biodegradable nanoparticles delivering a recombinant Flt23k intraceptor plasmid homes to neovascular lesions in the retina and regresses CNV in primate and murine AMD models. Moreover, this treatment suppressed subretinal fibrosis, which is currently not addressed by clinical therapies. Murine vision, as tested by OptoMotry, significantly improved with nearly 40% restoration of visual loss induced by CNV. We found no evidence of ocular or systemic toxicity from nanoparticle treatment. These findings offer a nanoparticle-based platform for targeted, vitreous-sparing, extended-release, nonviral gene therapy.