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.

Green synthesis of polysaccharide-based inorganic nanoparticles and biomedical aspects

“…Considering that tumor cells have different receptors on their surface, many studies have focused on developing NPs with specific moieties such as ligands, antibiotics, and peptides on the surface that can uptake by the tumor cells. Nevertheless, the chemical bonding strategies to attach the moieties on the particle surface may negatively affect the configuration of the binding site and consequently decrease the binding affinity [118]. Considering this, hyaluronic acid as a natural linear polysaccharide can bond to the surface of AuNPs, which could be correlated and recognized by the tested cancer cell CD 44 receptors [118].…”

“…Nevertheless, the chemical bonding strategies to attach the moieties on the particle surface may negatively affect the configuration of the binding site and consequently decrease the binding affinity [118]. Considering this, hyaluronic acid as a natural linear polysaccharide can bond to the surface of AuNPs, which could be correlated and recognized by the tested cancer cell CD 44 receptors [118]. Therefore, polysaccharide conjugated AuNPs may be considered as potential candidates for targeted delivery of therapeutic agents.…”

Preparation, Characterization and Application of Polysaccharide-Based Metallic Nanoparticles: A Review

“…Besides, polysaccharide-based AuNPs revealed desirable optical, electrical and chemical properties, which enabled to display high-amplitude photoacoustic signals in the cancer cells, suggesting promising potential in photoacoustic image-guided drug release and synergistic chemo-photoacoustic therapy [142,146]. Much evidence suggests that there are many receptors on the cell surface, which are responsible for the interaction between PMNPs and the microenvironment around the cells [147]. Based on this knowledge, hyaluronic acid supported AuNPs and Gracilaria lemaneiformis polysaccharide-based SeNPs achieved their anticancer effects by recognizing the receptors of CD44 and α v β 3 integrin in specific cancer cells, respectively [147,148], suggesting a new strategy for the design of targeted drug delivery.…”

“…Much evidence suggests that there are many receptors on the cell surface, which are responsible for the interaction between PMNPs and the microenvironment around the cells [147]. Based on this knowledge, hyaluronic acid supported AuNPs and Gracilaria lemaneiformis polysaccharide-based SeNPs achieved their anticancer effects by recognizing the receptors of CD44 and α v β 3 integrin in specific cancer cells, respectively [147,148], suggesting a new strategy for the design of targeted drug delivery. Another promising site-targeted type of MNPs was magnetic nanoparticles, which could be directed at the specific tissues by means of an external magnetic field and its significance in the anticancer drug delivery had been well discussed in the review [107].…”

The Effect of Quasi-Spherical Gold Nanoparticles on Two-Photon Induced Reactive Oxygen Species for Cell Damage

“…If a high-power CW laser is used to irradiate cells treated with GNPs, the generated heat damages proteins and other indispensable enzyme structures in the vicinity of GNPs, which leads to cell necrosis [ 5 , 6 ]. In addition, the apoptosis of these GNP-treated cells irradiated by a nanosecond-pulsed laser was also reported [ 7 ]. This is because that the transient heat around GNPs induces nanobubbles to disrupt the cytoskeletons, leading to cell lysis [ 7 ].…”