Indocyanine Green-Loaded PLGA Nanoparticles Conjugated with Hyaluronic Acid Improve Target Specificity in Cervical Cancer Tumors

Abstract

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.

Recent status and trends of nanotechnology in cervical cancer: a systematic review and bibliometric analysis

“…The efficiency of HINPs in delivering in vivo and the efficiency of free ICG in cervical cancer tumors were compared. Overall, HINPs have the potential to enhance NIR fluorescence image-guided surgery by assisting in the visualization of CD44-positive cervical cancer ( 75 ).…”

Hyaluronic acid in gynecology and obstetrics

“…The stability of HINP was confirmed at pH 5.0-8.0. It was shown, that compared to free ICG, HINPs had significantly higher internalization by cervical cancer cells than normal cells (p <0.001) and significantly higher accumulation in tumors (p <0.001) [22].…”

The utilization of nanotechnology in the female reproductive system and related disorders

“…Nanoparticles adorned with ligand-modified fluorescent dyes effectively zero in on lesions, thereby facilitating initial diagnosis and subsequent treatment. Notably, Choi et al accomplished the successful development of nanoparticles that target CD44-overexpressing cervical cancer cells, employing near-infrared FI to scrutinize tumors in vivo and trace metastatic cancer cells [ 16 ]. Additionally, Alomari et al harnessed tamoxifen (TAM) and poly(methyl methacrylate) nanoparticles loaded with Nile red to facilitate the delivery of TAM to ER-negative cervical cancer cells, thereby elucidating drug internalization [ 17 ].…”