2. Academic Validation
  3. Intravenous Multifunctional Nanotherapy for Treating Dry Age-Related Macular Degeneration

Intravenous Multifunctional Nanotherapy for Treating Dry Age-Related Macular Degeneration

  • Adv Healthc Mater. 2025 Aug 19:e02925. doi: 10.1002/adhm.202502925.
Xinyi Zhao 1 2 3,  Weiyi Xia 1 2 3,  Yu Wang 4,  Yihan Zhang 1 2 3,  Zheng Zhou 4,  Peixin Liu 5,  Shilin Zhang 4,  Zihan Zheng 1 2 3,  Weiai Shen 1 2 3,  Shujie Zhang 1 2 3,  Jing Yao 1 2 3,  Tao Sun 4 6,  Chen Jiang 4 7,  Chen Zhao 1 2 3
Affiliations

Affiliations

  • 1 Department of Ophthalmology and Vision Science, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China.
  • 2 Key laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China.
  • 3 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China.
  • 4 Key Laboratory of Smart Drug Delivery (Ministry of Education), Minhang Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Pharmacy, Fudan University, Shanghai, 201203, China.
  • 5 Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, 53705, USA.
  • 6 Quzhou Fudan Institute, Quzhou, 324003, China.
  • 7 Department of Digestive Diseases, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.
PMID: 40827631 DOI: 10.1002/adhm.202502925
Abstract

Retinal pigment epithelium (RPE) degeneration is the pathological hallmark of multifactorial dry age-related macular degeneration (dAMD). Mounting evidence implicates oxidative stress and aberrant activation of mammalian target of rapamycin (mTOR) as key drivers of this process. Recent studies have shown that simultaneous modulation of these pathways may offer therapeutic benefit. However, clinical trials of rapamycin, an mTOR Inhibitor widely employed in retinal research, have demonstrated limited efficacy, potentially due to poor bioavailability and paradoxical effects on RPE and photoreceptors. To overcome these challenges, APMNP@Rapa, a rapamycin-loaded, methionine-based ROS-responsive polymeric micellar system functionalized with an Ab peptide for active targeting of damaged RPE is developed. The micelles self-assemble from poly(ethylene glycol) - poly-methionine copolymers, leveraging methionine's endogenous nature and innate biocompatibility as an innovative ROS-responsive motif. This design yields particles with exceptional circulation stability and enhanced biocompatibility. In the high-ROS microenvironment of diseased RPE, APMNP@Rapa triggers on-demand rapamycin release. In a sodium iodate (NaIO3)-induced RPE oxidative stress model, APMNP@Rapa simultaneously inhibited aberrant mTOR activation, attenuated oxidative damage, and suppressed inflammatory response. These combined effects resulted in a marked preservation of the retina against degradation. Overall, the research establishes a paradigm for intravenous treatment of dAMD using multifunctional nanotherapy.

Keywords

age‐related macular degeneration; intravenous injection; mTOR signaling; multifunction; oxidative stress.

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