title: Selective Targeting and Restrictive Damage for Nonspecific Cells by Pulsed Laser-Activated Hyaluronan-Gold Nanoparticles.
abstract: Herein, we describe an approach that immobilizes low-molecular-weight hyaluronic acid (low-MW HA) on the surface of gold nanoparticles (GNPs), which can serve as a cellular probe and photodamage media, to evaluate the selectivity and efficiency of HA-based GNPs (HGNPs) as a mediator of laser-induced photothermal cell damage. In addition, it is known that solid tumors contain a higher content of low-MW HA than normal tissues. Thus, we used low-MW HA rather than high-MW HA used in other studies. In the present study, we conjugated low-MW HA, which is a linear polysaccharide with a disaccharide repeat unit, to prevent a reduction of the ligand-receptor binding efficiency in contrast to the conjugation of protein or peptides, which have unique three-dimensional structures. Three cell lines-MDA-MB-435 S (with CD44), MDA-MB-453 and NIH/3T3 (both are without CD44)-were investigated in the study, and qualitative observations were conducted by dark-field microscopy and laser scanning confocal microscopy (LSCM). In addition, quantitative measurements calculated using inductively coupled plasma emissions were taken for comparison. Our results showed that within the same treatment time, the uptake dosage of HGNPs by the MDA-MB-435 S cells was higher than that by the MDA-MB-453 and NIH 3T3 cells. Meanwhile, HGNPs uptake by the untreated MDA-MB-435 S cells was higher than that of MDA-MB-435 S cells with CD44 blocked by antibodies or silencing CD44 expression. This result implies that receptor-mediated endocytosis can enhance the cellular uptake of HGNPs. In addition, when exposed to a low-power pulsed laser, the former cell morphologies showed a more laser-induced giant plasma membrane vesicles (GPMV) than the latter morphologies. Therefore, this study utilized the specific photothermal property of HA-modified GNPs with laser-induced blebs to create a possible new method for medical applications.
authors.affiliation: Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University , Taoyuan 333, Taiwan.
authors.forename: Lih-Rou
authors.initials: LR
authors.lastname: Rau
authors.affiliation: Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University , Taoyuan 333, Taiwan.
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Tsao
authors.affiliation: Department of Mechanical Engineering, Chang Gung University , Taoyuan 333, Taiwan.|Center for Biomedical Engineering, Chang Gung University , Taoyuan 333, Taiwan.|Institute for Radiological Research, Chang Gung University and Chang Gung Memorial Hospital , Taoyuan 333, Taiwan.|Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital , Linkou 333, Taiwan.
authors.forename: Jiunn-Woei
authors.initials: JW
authors.lastname: Liaw
authors.affiliation: Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University , Taoyuan 333, Taiwan.|Center for Biomedical Engineering, Chang Gung University , Taoyuan 333, Taiwan.|Department of Orthopaedic Surgery, Chang Gung Memorial Hospital , Linkou 333, Taiwan.
authors.forename: Shiao-Wen
authors.initials: SW
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002470:Cell Survival / Q000528:radiation effects; D004705:Endocytosis; D005260:Female; D006046:Gold / Q000737:chemistry*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry*; D007834:Lasers; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D014407:Tumor Cells, Cultured
chemical_list: D018960:Hyaluronan Receptors; D006046:Gold; D006820:Hyaluronic Acid