E-POSTER DETAIL | 11th Asia Pacific Tele Ophthalmology Society Symposium

Title
A Programmable and Intrinsically Therapeutic tFNA Nanoplatform for Versatile Multi-Target Ocular Fundus Therapy

Authors
Ruobing Wang

Presenting
Ruobing Wang

PURPOSE:
Multifactorial retinal diseases, such as age-related macular degeneration (AMD), are driven by concurrent neovascularization and inflammation. Leveraging the structural superiority and spatial programmability of tetrahedral framework nucleic acids (tFNAs), this study aims to develop a multi-efficacy microinvasive nanoplatform. We propose that tFNA serves not merely as an intrinsically anti-inflammatory nanocarrier; its unique architecture essentially provides a universal platform for the simultaneous loading of other diverse drug targets, broadening the horizon beyond conventional anti-VEGF monotherapies.

PURPOSE:

Multifactorial retinal diseases, such as age-related macular degeneration (AMD), are driven by concurrent neovascularization and inflammation. Leveraging the structural superiority and spatial programmability of tetrahedral framework nucleic acids (tFNAs), this study aims to develop a multi-efficacy microinvasive nanoplatform. We propose that tFNA serves not merely as an intrinsically anti-inflammatory nanocarrier; its unique architecture essentially provides a universal platform for the simultaneous loading of other diverse drug targets, broadening the horizon beyond conventional anti-VEGF monotherapies.

METHODS:
Utilizing the highly modifiable vertices of the tFNA skeleton, we engineered a dual-action nanomedicine loaded with anti-VEGFA aptamers (apt-tFNAs) as a proof-of-concept for its versatile loading capacity. Following microinvasive subconjunctival administration to penetrate the outer blood-retinal barrier (oBRB), we evaluated both the targeted anti-angiogenic effects of the loaded aptamers and the inherent anti-inflammatory/antioxidant properties of the structural carrier itself in vivo and in vitro.

METHODS:

Utilizing the highly modifiable vertices of the tFNA skeleton, we engineered a dual-action nanomedicine loaded with anti-VEGFA aptamers (apt-tFNAs) as a proof-of-concept for its versatile loading capacity. Following microinvasive subconjunctival administration to penetrate the outer blood-retinal barrier (oBRB), we evaluated both the targeted anti-angiogenic effects of the loaded aptamers and the inherent anti-inflammatory/antioxidant properties of the structural carrier itself in vivo and in vitro.

RESULTS:
The apt-tFNA complex successfully permeated the oBRB intact. While the loaded aptamers precisely inhibited choroidal neovascularization, the naked tFNA carrier independently mitigated oxidative stress and inflammatory pathways in retinal cells. This intrinsic synergy validated that the structural integrity of tFNAs efficiently supports functional multiplexing without compromising ocular penetrability, firmly establishing its feasibility for conjugating other distinct pharmacological moieties.

RESULTS:

The apt-tFNA complex successfully permeated the oBRB intact. While the loaded aptamers precisely inhibited choroidal neovascularization, the naked tFNA carrier independently mitigated oxidative stress and inflammatory pathways in retinal cells. This intrinsic synergy validated that the structural integrity of tFNAs efficiently supports functional multiplexing without compromising ocular penetrability, firmly establishing its feasibility for conjugating other distinct pharmacological moieties.

CONCLUSIONS:
Featuring exceptional structural advantages, tFNAs represent a highly efficient, intrinsically therapeutic nanoplatform. By acting simultaneously as an active anti-inflammatory agent and a highly penetrable vehicle, it provides a robust structural foundation for the seamless integration of other diverse therapeutic targets, offering a highly programmable, multi-valent strategy for complex ocular disease management.

CONCLUSIONS:

Featuring exceptional structural advantages, tFNAs represent a highly efficient, intrinsically therapeutic nanoplatform. By acting simultaneously as an active anti-inflammatory agent and a highly penetrable vehicle, it provides a robust structural foundation for the seamless integration of other diverse therapeutic targets, offering a highly programmable, multi-valent strategy for complex ocular disease management.