The comparative effect of wrapping solid gold nanoparticles and hollow gold nanoparticles with doxorubicin-loaded thermosensitive liposomes for cancer thermo-chemotherapy

Abstract

Since conventional chemotherapy is a systemic treatment that affects the body globally and will not concentrate inside the tumor, it causes adverse side effects to patients. In this study, doxorubicin (DOX) together with solid gold nanoparticles (GNPs) or hollow gold nanoparticles (HGNPs), respectively, is loaded inside thermosensitive liposomes (GNPs&DOX-TLs and HGNPs&DOX-TLs), where the GNPs and HGNPs act as a "nanoswitch" for killing tumor cells directly by hyperthermia and triggering DOX release from TLs in the tumor quickly by near infrared laser (NIR) illumination. In addition, this study investigated the photothermal transformation ability, NIR triggered drug release behavior, and the intracellular uptake and cytotoxicity of breast tumor cells and the thermo-chemotherapy mediated by the co-delivery of GNPs&DOX-TLs and HGNPs&DOX-TLs. GNPs and HGNPs had very different light-to-heat transduction efficiencies, while the hollow HGNPs had the advantage of NIR surface plasmon tunability, resulting in the photothermal ablation of tumors with 800 nm light penetration in tissue. The prepared HGNPs&DOX-TLs exhibited a spherical shape with a diameter of 190 nm and a ξ potential of -29 mV, which were steadily dispersed for at least one month. The co-encapsulated DOX was released under hyperthermia caused by NIR-responsive HGNPs and the local drug concentration increased along with the disintegration of the liposomal membrane. This co-delivery of HGNPs&DOX-TLs produced a synergistic cytotoxicity response, thereby enhancing anticancer efficacy 8-fold and increasing the survival time compared to GNPs&DOX-TLs. This work suggested that the co-delivery of HGNPs&DOX-TLs followed by burst-release of DOX using NIR-responsive HGNPs sensitized cancer cells to the chemotherapeutic compound, which provided a novel concept for the combination strategy of chemotherapy and photothermal therapy. These results suggest that the markedly improved therapeutic efficacy and decreased systemic toxicity of the NPs presented in this study hold significant potential for future cancer treatment.

A polyoxyethylene sorbitan oleate modified hollow gold nanoparticle system to escape macrophage phagocytosis designed for triple combination lung cancer therapy via LDL-R mediated endocytosis

“…HGNPs and HGNPs-DOX were prepared as previously described (Li et al., 2018 ) and is summarized in the Supporting Information section. An appropriate amount of PSO-LA was added to the prepared HGNP-DOX solution and incubated at 37 °C for 8 h. The PSO-HGNPs-DOX solution prepared above was centrifuged at 10,000 rpm for 15 min, the unreacted PSO-LA in the supernatant was discarded, and the precipitate was re-dissolved in ultrapure water to obtain PSO-HGNPs- DOX.…”

“…Further, local surface plasmon resonance (LSPR) is a unique property of noble metal nanoparticles. When the frequency of incident light is equivalent to the vibration frequency of AuNPs, they can strongly absorb photon energy (Li et al., 2018 ; Wang et al., 2019 ). Because tissue and blood have low absorption and scattering of near-infrared light (NIR) in the 650–900 nm range, NIR in this range can penetrate nearly 10 cm without damaging healthy tissue (Pastrana, 2012 ); this is the depth of most lung tumors.…”

“…Of all of the possible AuNPs geometries, hollow gold nanoparticles (HGNPs) are the most attractive for lung cancer combination therapies since their hollow structure can form a larger absorption cross section and the LSPR can be between 650 and 900 nm by simply adjusting the thickness and size of the outer shell. HGNPs can have a higher photothermal conversion effect and are widely used for their photothermal properties for effective tumor treatment (Li et al., 2018 ). HGNPs can also be used as radiosensitizers and can produce strong photoelectric absorption and secondary electrons after irradiation, thus, accelerating cancer cell DNA strand breakage (Rahman et al., 2014 ).…”

<p>Applications of Inorganic Nanomaterials in Photothermal Therapy Based on Combinational Cancer Treatment</p>

“…The release of drugs is limited without NIR irradiation and the drugs are rapidly released when photothermal agents are triggered by NIR irradiation so a lower dosage of drugs is required to achieve the ideal result. 49 Furthermore, if the release system is enough, intelligent drug-releasing nanoparticles can be immediately ceased when the NIR laser is switched off. 50 For example, Zhao et al developed an inorganic materialhollow structured polymer-silica nanohybrid (HPSN) as a nanocarrier to deliver the photothermal agent palladium phthalocyanine and chemotherapeutic drug paclitaxel.…”

A DM1-doped porous gold nanoshell system for NIR accelerated redox-responsive release and triple modal imaging guided photothermal synergistic chemotherapy

“…Similar results ( Figure 3B) were obtained when using an infrared thermal image instrument, which demonstrated that the DM1 modification would not affect the photothermal conversion abilities of the PGNSs. Hence, the photothermal conversion abilities of both the modified and unmodified PGNSs could facilitate hyperthermia relatively rapidly, thus, enabling a thermotherapeutic effect and the global or local ablation of tumor tissues at temperatures of 39-42°C (49) .…”