Pulsed-laser irradiation of multifunctional gold nanoshells to overcome trastuzumab resistance in HER2-overexpressing breast cancer

• Published in: Journal of experimental & clinical cancer research Vol. 38; no. 1; p. 306
• Main Authors: Nunes, Toni, Pons, Thomas, Hou, Xue, Van Do, Khanh, Caron, Benoît, Rigal, Marthe, Di Benedetto, Mélanie, Palpant, Bruno, Leboeuf, Christophe, Janin, Anne, Bousquet, Guilhem
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12-07-2019; BioMed Central; BMC
• Subjects: Animals; Antibodies; Antineoplastic agents; Antineoplastic Agents, Immunological - administration & dosage; Biotechnology; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Cancer; Cancer metastasis; Cardiology and cardiovascular system; Cell Line, Tumor; Cell Survival - drug effects; Complications and side effects; Development and progression; Disease Models, Animal; Dosage and administration; Drug Carriers; Drug resistance; Drug Resistance, Neoplasm - genetics; Drug therapy; Female; Femtosecond laser; Fever; Functionalized gold nanoparticles; Gene Dosage; Gene Expression Regulation; Genetic aspects; Gold - chemistry; HER2-overexpressing breast cancer; Human health and pathology; Humans; Lasers; Life Sciences; Magnetic Resonance Imaging; Mice; Nanoparticles; Nanoshells - chemistry; Neovascularization, Pathologic - drug therapy; Phototherapy; Photothermal therapy; Povidone; Receptor, ErbB-2 - genetics; Resistance reversion; Silicon Dioxide - chemistry; Toxicity; Toxicology; Trastuzumab; Trastuzumab - administration & dosage; Trastuzumab resistance; Tumors; Xenograft Model Antitumor Assays; France; Photothermal therapy; Femtosecond laser; Trastuzumab resistance; Functionalized gold nanoparticles; Resistance reversion; HER2-overexpressing breast cancer
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-019-1305-x

HER2-overexpressing metastatic breast cancers are challenging practice in oncology when they become resistant to anti-HER2 therapies such as trastuzumab. In these clinical situations, HER2-overexpression persists in metastatic localizations, and can thus be used for active targeting using innovative therapeutic approaches. Functionalized gold nanoparticles with anti-HER2 antibody can be stimulated by near-infrared light to induce hyperthermia.
Here, hybrid anti-HER2 gold nanoshells were engineered for photothermal therapy to overcome trastuzumab resistance in HER2-overexpressing breast cancer xenografts.
When gold nanoshells were administered in HER2-tumor xenografts, no toxicity was observed. A detailed pharmacokinetic study showed a time-dependent accumulation of gold nanoshells within the tumors, significantly greater with functionalized gold nanoshells at 72 h. This enabled us to optimize the treatment protocol and irradiate the mice when the anti-HER2 gold nanoshells had accumulated most in the tumors. After weekly injections of anti-HER2 gold nanoshells, and repeated irradiations with a femtosecond-pulsed laser over four weeks, tumor growth was significantly inhibited. Detailed tissue microscopic analyses showed that the tumor growth inhibition was due to an anti-angiogenic effect, coherent with a preferential distribution of the nanoshells in tumor microvessels. We also showed a direct tumor cell effect with apoptosis and inhibition of proliferation, coherent with an immune-mediated targeting of tumor cells by anti-HER2 nanoshells.
This preclinical study thus supports the use of anti-HER2 gold nanoshells and photothermal therapy to overcome trastuzumab resistance in HER2-overexpressing breast cancer.