RGD-conjugated mesoporous silica-encapsulated gold nanorods enhance the sensitization of triple-negative breast cancer to megavoltage radiation therapy

Abstract

Multifunctional nanoprobes have great potential as effective radiosensitizers and drug carriers. RGD-modified gold nanorods could increase the uptake of nanoparticles via receptor-mediated endocytosis in integrin alphaV beta3-overexpressing breast cancer cells, which could enhance the effects of radiation on tumor cells, leading to further radiosensitization. The purpose of our study was to demonstrate that RGD-conjugated mesoporous silica-encapsulated gold nanorods significantly enhanced the sensitization of triple-negative breast cancer to megavoltage energy. The results indicated that RGD-conjugated mesoporous silica-encapsulated gold nanorod multifunctional nanoprobes could achieve radiosensitization in vitro and in vivo, which suggests the potential translation of this nanotechnology to clinical applications in tumor-targeting and selective therapy.

Keywords:

• gold nanorods
• triple-negative breast cancer
• Arg-Gly-Asp peptides
• integrin alphaV beta3
• megavoltage radiation therapy

Supplementary materials

Figure S1 Zeta potential distribution.

Notes: (A) The zeta potential of the GNRs@mSiO₂-NH₂ nanoparticles was 35.1±7.01 mV; (B) the zeta potential of the pGNRs@mSiO₂-RGD nanoprobes was 17.5±4.37 mV. GNRs@mSiO₂-NH₂, mesoporous silica-encapsulated gold nanorods conjugated with NH₂ groups; pGNRs@mSiO₂-RGD, RGD-conjugated mesoporous silica-encapsulated gold nanorods; RGD, arginine–glycine–aspartic acid (Arg-Gly-Asp, RGD) peptides.

Figure S2 Hydrodynamic diameters of pGNRs@mSiO₂-RGD nanoprobes at different periods of time (0.5 hours, 24 hours, and 1 month), they were 78.43±1.32 nm, 80.94±2.69 nm, and 81.52±1.80 nm, respectively.

Notes: pGNRs@mSiO₂-RGD, RGD-conjugated mesoporous silica-encapsulated gold nanorods; RGD, arginine–glycine–aspartic acid (Arg-Gly-Asp, RGD) peptides; PSD, particle size distribution.

Figure S3 Flow cytometry analysis of MDA-MB-231 cell apoptosis.

Notes: (A–F) Apoptosis of MDA-MB-231 cells exposed to pGNRs@mSiO₂ or pGNRs@mSiO₂-RGD nanoprobes for 24 hours with or without 6 MV X-rays (6 Gy). (A) Control, (B) pGNRs@mSiO₂, (C) pGNRs@mSiO₂-RGD, (D) RT, (E) pGNRs@mSiO₂ + RT, and (F) pGNRs@mSiO₂-RGD + RT. pGNRs@mSiO₂, mesoporous silica-encapsulated gold nanorods; pGNRs@mSiO₂-RGD, RGD-conjugated mesoporous silica-encapsulated gold nanorods; RGD, arginine–glycine–aspartic acid (Arg-Gly-Asp) peptides. Variables B1–B4 respectively refer to necrotic cells, early stage apoptotic cells, normal cells, and late stage apoptotic cells.

Abbreviation: RT, radiation.

Figure S4 Flow cytometry analysis of G₂/M cell cycle arrest in MDA-MB-231 cells.

Notes: (A–F) Percentage of MDA-MB-231 cells in G₂/M after exposure to pGNRs@mSiO₂ or pGNRs@mSiO₂-RGD nanoprobes for 24 hours with or without 6 MV X-rays (6 Gy). (A) Control, (B) pGNRs@mSiO₂, (C) pGNRs@mSiO₂-RGD, (D) RT, (E) pGNRs@mSiO₂ + RT, and (F) pGNRs@mSiO₂-RGD + RT. pGNRs@mSiO₂, mesoporous silica-encapsulated gold nanorods; pGNRs@mSiO₂-RGD, RGD-conjugated mesoporous silica-encapsulated gold nanorods; RGD, arginine–glycine–aspartic acid (Arg-Gly-Asp) peptides. G₀/G₁, G₂/M, and S are cell phases.

Abbreviation: RT, radiation.

Figure S5 Orthotopic nude mouse model of TNBC (arrow).

Abbreviation: TNBC, triple-negative breast cancer.

Figure S6 TNBC tumor tissues treated with pGNRs@mSiO₂-RGD + RT (10 Gy).

Notes: The pGNRs@mSiO₂-RGD (arrows) were clustered in the tumor cell cytoplasm. Scale bar =2 μm, 9,700×. pGNRs@mSiO₂-RGD, RGD-conjugated mesoporous silica-encapsulated gold nanorods; RGD, arginine–glycine–aspartic acid (Arg-Gly-Asp) peptides.

Abbreviations: TNBC, triple-negative breast cancer; RT, radiation.

Acknowledgments

This work was financially supported by a research grant (YG2012ZD02, 2JC1407400) from Shanghai Jiao Tong University and the Science and Technology Commission of Shanghai, People’s Republic of China, and a grant (81272506, 61227017) from the National Natural Science Foundation of China.

Disclosure

The authors report no conflicts of interest in this work.