Yolk–Shell-Type Gold Nanoaggregates for Chemo- and Photothermal Combination Therapy for Drug-Resistant Cancers

Abstract

Epithelial ovarian cancer is a gynecological cancer with the highest mortality rate, and it exhibits resistance to conventional drugs. Gold nanospheres have gained increasing attention over the years as photothermal therapeutic nanoparticles, owing to their excellent biocompatibility, chemical stability, and ease of synthesis; however, their practical application has been hampered by their low colloidal stability and photothermal effects.In the present study, we developed a yolk−shell-structured silica nanocapsule encapsulating aggregated gold nanospheres (aAuYSs) and examined the photothermal effects of aAuYSs on cell death in drug-resistant ovarian cancers both in vitro and in vivo. The aAuYSs were synthesized using stepwise silica seed synthesis, surface amino functionalization, gold nanosphere decoration, mesoporous organosilica coating, and selective etching of the silica template. Gold nanospheres were agglomerated in the confined silica interior of aAuYSs, resulting in the red-shifting of absorbance and enhancement of the photothermal effect under 808 nm laser irradiation. The efficiency of photothermal therapy was first evaluated by inducing aAuYS-mediated cell death in A2780 ovarian cancer cells, which were cultured in a two-dimensional culture and a three-dimensional spheroid culture. We observed that photothermal therapy using aAuYSs together with doxorubicin treatment synergistically induced the cell death of doxorubicin-resistant A2780 cancer cells in vitro. Furthermore, this type of combinatorial treatment with photothermal therapy and doxorubicin synergistically inhibited the in vivo tumor growth of doxorubicin-resistant A2780 cancer cells in a xenograft transplantation model. These results suggest that photothermal therapy using aAuYSs is highly effective in the treatment of drug-resistant cancers.

Inhibitory Effect of Etravirine, a Non-Nucleoside Reverse Transcriptase Inhibitor, via Anterior Gradient Protein 2 Homolog Degradation against Ovarian Cancer Metastasis

“…The adriamycin concentration was 1 nM, and the surviving cells were treated with two concentrations. The process repeated up to 128 nM adriamycin to increase the resistance to adriamycin [60]. Primary human umbilical vein endothelial cells (HUVECs) were purchased from ScienCell Research Laboratories (CA, USA).…”

Research Progress of Photothermal Nanomaterials in Multimodal Tumor Therapy

“…At present, several gold nanomaterials with unique size and morphology have been developed, including nanorods, nanospheres, nanostars, nanocages, and nanoshells, among others. Choe et al ( 30 ) loaded high concentration gold nanoparticles into mesoporous silica nanocapsules to form yolk-shell-structured gold nanospheres (aAuYSs) to study their photothermal effect on drug-resistant ovarian cancer cells. Under 808-nm laser irradiation, the cultured cancer cells were eliminated when the concentration of aAuYSs was 300 μg/mL.…”

Doxorubicin-encapsulated thermosensitive liposome-functionalized photothermal composite scaffolds for synergistic photothermal therapy and chemotherapy

“…[14][15][16] Thus, PTT and chemotherapy have been combined to achieve maximal therapeutic efficiency. 17,18 Therapeutic PTT agents and anticancer drugs can be systematically administered through intravenous injection; however, this route has problems related to rapid clearance by the mononuclear phagocyte system, low accumulation in the targeted cancer cells and side effects at high dosages. 19,20 The low accumulation and retention of PTT agents and anticancer drugs in the cancer site has been recognized as the main factor leading to treatment failure.…”