Indocyanine Green-Loaded PLGA Nanoparticles Conjugated with Hyaluronic Acid Improve Target Specificity in Cervical Cancer Tumors
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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.
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.
참고문헌 (29)
- Sung H, "Global cancer statistics 2020 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J Clin, 71, pp.209~249 (2021)
- Ferlay J, "Estimating the global cancer incidence and mortality in 2018 : GLOBOCAN sources and methods", Int J Cancer, 144, pp.1941~1953 (2019)
- Li B, "Paclitaxel-loaded lignin particle encapsulated into electrospun PVA", PVP composite nanofiber for effective cervical cancer cell inhibition, 2021, pp.32, 015101~
- Janicek MF, "Cervical cancer : prevention, diagnosis, and therapeutics", CA Cancer J Clin, 51, pp.92~114 (2001)
- Gioux S, "Image-guided surgery using invisible near-infrared light : fundamentals of clinical translation", Mol Imaging, 9, pp.237~255 (2010)
- Lee BT, "The FLARE intraoperative near-infrared fluorescence imaging system : a first-in-human clinical trial in perforator flap breast reconstruction", Plast Reconstr Surg, 126, pp.1472~1481 (2010)
- Buda A, "Nearinfrared fluorescence-guided sentinel node mapping of the ovary with indocyanine green in a minimally invasive setting : a feasible study", J Minim Invasive Gynecol, 24, pp.165~170 (2017)
- Holloway RW, "Detection of sentinel lymph nodes in patients with endometrial cancer undergoing robotic-assisted staging : a comparison of colorimetric and fluorescence imaging", Gynecol Oncol, 126, pp.25~29 (2012)
- West W, "The dimeric state of cyanine dyes", J Phys Chem, 69, pp.1894~1903 (1965)
- Zhou JF, "Laser surgery: advanced characterization, therapeutics and systems IV", pp.495~505 (1994), SPIE
- van den Biesen PR, "Yield of fluorescence from indocyanine green in plasma and flowing blood", Ann Biomed Eng, 23, pp.475~481 (1995)
- Desmettre T, "Fluorescence properties and metabolic features of indocyanine green(ICG)as related to angiography", Surv Ophthalmol, 45, pp.15~27 (2000)
- Li Y, "Localized electric field of plasmonic nanoplatform enhanced photodynamic tumor therapy", ACS Nano, 8, pp.11529~11542 (2014)
- Wang H, "Indocyanine green-incorporating nanoparticles for cancer theranostics", Theranostics, 8, pp.1227~1242 (2018)
- Hsiao YH, "Phloretin suppresses metastasis by targeting protease and inhibits cancer stemness and angiogenesis in human cervical cancer cells", Phytomedicine, 62, pp.152964~ (2019)
- Wiegand BD, "The use of indocyanine green for the evaluation of hepatic function and blood flow in man", Am J Digest Dis, 5, pp.427~436 (1960)
- Manchanda R, "Preparation and characterization of a polymeric(PLGA)nanoparticulate drug delivery system with simultaneous incorporation of chemotherapeutic and thermo-optical agents", Colloids Surf B Biointerfaces, 75, pp.260~267 (2010)
- Bahmani B, "Effect of polyethylene glycol coatings on uptake of indocyanine green loaded nanocapsules by human spleen macrophages in vitro", J Biomed Opt, 16, pp.051303~ (2011)
- Saxena V, "Polymeric nanoparticulate delivery system for Indocyanine green : biodistribution in healthy mice", Int J Pharm, 308, pp.200~204 (2006)
- Hill TK, "Indocyanine green-loaded nanoparticles for image-guided tumor surgery", Bioconjug Chem, 26, pp.294~303 (2015)
- Chen C, "The biology and role of CD44 in cancer progression : therapeutic implications", J Hematol Oncol, 11, pp.64~ (2018)
- Tran TH, "Hyaluronic acid-coated solid lipid nanoparticles for targeted delivery of vorinostat to CD44 overexpressing cancer cells", Carbohyd Polym, 114, pp.407~415 (2014)
- Yan HM, "Hyaluronic acid-modified didecyldimethylammonium bromide", d-a-tocopheryl polyethylene glycol succinate mixed micelles for delivery of baohuoside I against non-small cell lung cancer : in vitro and in vivo evaluation, 2017, pp.24, 30~39
- Xin Y, "Development of PLGA-lipid nanoparticles with covalently conjugated indocyanine green as a versatile nanoplatform for tumor-targeted imaging and drug delivery", Int J Nanomed, 11, pp.5807~5820 (2016)
- Park HS, "Hyaluronic acid", poly(β-amino ester)polymer nanogels for cancer-cell-specific NIR fluorescence switch, 2012, pp.33, 1549~1555
- Wilhelm S, "Analysis of nanoparticle delivery to tumours", Nat Rev Mater, 1, pp.16014~ (2016)
- Wojtkowiak JW, "Drug resistance and cellular adaptation to tumor acidic pH microenvironment", Mol Pharm, 8, pp.2032~2038 (2011)
- Moghimi SM, "A two-stage poly(ethylenimine)-mediated cytotoxicity : implications for gene transfer", therapy, 2005, pp.11, 990~995
- Wan L, "Hyaluronic acid modified mesoporous carbon nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells", Nanotechnology, 27, pp.135102~ (2016)