Purpose Indocyanine green (ICG) is a promising agent for intraoperative visualization of tumor tissues and sentinel lymph nodes in early-stage gynecological cancer. However, it has some limitations, including a short half-life and poor solubility in aqueous solutions. This study aimed to enhance the efficacy of near-infrared (NIR) fluorescence imaging by overcoming the shortcomings of ICG using a nano-drug delivery system and improve target specificity in cervical cancer. Materials and Methods ICG and poly(lactic-co-glycolic acid) (PLGA) conjugated with polyethylenimine (PEI) were assembled to enhance stability. Hyaluronic acid (HA) was coated on PEI-PLGA-ICG nanoparticles to target CD44-positive cancer cells. The manufactured HA-ICG-PLGA nanoparticles (HINPs) were evaluated in vitro and in vivo on cervical cancer cells (SiHa; CD44+) and human dermal cells (ccd986sk; CD44-), respectively, using NIR imaging to compare intracellular uptake and to quantify the fluorescence intensities of cells and tumors. Results HINPs were confirmed to have a mean size of 200 nm and a zeta-potential of 33 mV using dynamic light scattering. The stability of the HINPs was confirmed at pH 5.0–8.0. Cytotoxicity assays, intracellular uptake assays, and cervical cancer xenograft models revealed that, compared to free ICG, the HINPs had significantly higher internalization by cervical cancer cells than normal cells ( p <0.001) and significantly higher accumulation in tumors ( p <0.001) via CD44 receptor-mediated endocytosis. Conclusion This study demonstrated the successful application of HINPs as nanocarriers for delivering ICG to CD44-positive cervical cancer, with improved efficacy in NIR fluorescence imaging.

Background Ototoxicity currently has no available treatment other than medication withdrawal as soon as toxicity is suspected. The human inner ear organs have little potential for regeneration; thus, ototoxicity-induced hair cell injury is deemed permanent. Dexamethasone (Dexa) is a synthetic steroid analog that has significant potential for otoprotection in the treatment of various inner ear diseases; however, its low absorption into the inner ear prevents significant recovery of function. Nanoparticles facilitate targeted drug delivery, stabilize drug release, and increase half-life of the drug. Methods This study aimed to develop poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded superparamagnetic iron oxide nanoparticles (SPIONs) and Dexa (PSD-NPs) to control localized drug delivery by magnetic attraction in the treatment of ototoxicity-induced hearing loss. PSD-NPs and without SPIONs (PD-NPs) were prepared using a nanoprecipitation method. Results Using an inner ear simulating system, we confirmed that PSD-NPs has an otoprotective effect in organotypic culture that is enhanced by magnetic attraction. PSD-NPs delivered via intrabullar injection in a magnetic field penetrated the inner ear and prevented hearing loss progression to a greater degree than equivalent doses of Dexa or PSD-NPs alone (day 28: ototoxic: 80.0 ± 0.0 dB; Dexa 100: 60.0 ± 15.5 dB; PSD 100: 50.0 ± 8.2 dB; PSD 100 with magnet: 22.5 ± 5.0 dB; P < 0.05). The protective effects were confirmed in various in vivo and in vitro models of ototoxicity. Conclusion Our findings suggest that SPIONs with Dexa and magnetic field application prevent the progression of ototoxicity-induced hearing loss through anti-apoptotic mechanisms in the inner ear.