Nanotechnology-based reformulation of AUY922 mitigates retinal toxicity and retains potent anti-tumor activity
- Nanomedicine. 2026 Jun:74:102957. doi: 10.1016/j.nano.2026.102957.
- 1. School of Dentistry, Taipei Medical University, Taipei, Taiwan.
- 2. Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
- 3. Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Taiwan.
- 4. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, and College of Medicine and Cancer for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Clinical Pharmacy and Pharmaceutical Science and Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
- 5. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Doctoral Program in Tissue Engineering and Regenerative Medicine, Biotechnology Center, National Chung Hsing University, Taichung, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan. Electronic address: [email protected].
AUY922, a heat-shock protein 90 inhibitor, shows broad antitumor activity but is limited by dose-limiting ocular toxicity. In this study, we engineered FLIM02, a PLGA/DSPE-PEG2000 (1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[poly(ethylene glycol)-2000])-based nanoparticle via single-emulsion, and evaluated its physicochemical profile, biodistribution, ocular safety, and efficacy. FLIM02 formed ∼100-nm particles with efficient encapsulation and retained stability after lyophilization. In tumor-bearing mice, LC-MS/MS biodistribution showed reduced ocular retention of AUY922 with preserved tumor exposure and comparable hepatic/renal distribution versus prototype. FLIM02 preserved retinal architecture as evidenced by reduced TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)-positive cells and attenuated GFAP induction, while maintaining antitumor activity in xenograft tumor models. No overt systemic toxicity was observed, supported by stable body weight, normal serum biochemical parameters, and absence of apparent pathological abnormalities in major organs. These findings support that nanoparticle reformulation can decouple antitumor efficacy from tissue-specific toxicity. FLIM02 suggests potential to reduce ocular toxicity while preserving antitumor activity, meriting further mechanistic studies and longitudinal preclinical models.