Antitumor Effect of 131I-Labeled Anti-VEGFR2 Targeted Mesoporous Silica Nanoparticles in Anaplastic Thyroid Cancer

Abstract

Anaplastic thyroid cancer (ATC) comprises approximately 2% of all thyroid cancers, and its median survival rate remains poor because of its resistance to conventional therapy. Vascular endothelial growth factor receptor (VEGFR)-targeted therapeutics-loaded mesoporous silica nanoparticles represent a major advance for angiogenesis imaging and inhibition in lethal cancers. In the present study, we aimed to assess whether 131I-labeled anti-VEGFR2 targeted mesoporous silica nanoparticles would have antitumor efficacy in an ATC tumor-bearing nude mouse model. Using in vitro and in vivo studies, we investigated the increased targeting ability and retention time in the anti-VEGFR2 targeted group using confocal microscopy and a γ counter. The tumor tissue radioactivity of the anti-VEGFR2 targeted group at 24 and 72 h after intratumoral injection was significantly higher than that of the non-targeted groups (all P < 0.05). Moreover, we found that radioactive accumulation was obvious even at 3 week post-injection in the anti-VEGFR2 targeted group via single-photon emission computed tomography/computed tomography, which was not seen at 3 day post-injection in the Na131I group. Meanwhile, compared with the non-targeted group, tumor growth in the targeted group was significantly inhibited, without causing apparent systemic toxic effects. Additionally, the median survival time in the targeted group (41 days) was significantly prolonged compared with that in the non-targeted (34 days) or Na131I (25 days) groups (both P < 0.01). Our data support the view that the as-developed 131I-labeled anti-VEGFR2 targeted mesoporous silica nanoparticles showed promising results in ATC tumor-bearing mouse model and such an approach might represent a novel therapeutic option for ATC.

Effect of mesoporous silica nanoparticles co‑loading with 17‑AAG and Torin2 on anaplastic thyroid carcinoma by targeting VEGFR2

“…Nanomaterials have been widely used in the field of biomedicine, including silica, liposomes, polymers, and gold and iron oxide nanoparticles (4,45). Compared to other silica nanomaterials, MSNs are widely used due to their higher surface area, non-toxic property, improved ductility and permeability, adjustable pore structure, chemically modifiable outer surface, and improved biological compatibility (45,46).…”

“…The synthesis of mesoporous silica nanoparticles (MSNs) was performed as previously reported (4,31). Briefly, cetyltrimethyl ammonium bromide (CTAB; Sigma-Aldrich; Merck KGaA) was dissolved in a solution of water (25 ml), ethanol (5 ml), and caustic soda solution (100 µl; 2 M) and heated to 75˚C under vigorous stirring conditions.…”

“…Among numerous silica materials, mesoporous silica nanoparticles (MSNs) have been widely investigated for biomedical applications such as controlled drug delivery, tissue engineering, and biological imaging especially as a tool for diagnosis and treatment of tumors (21,24,25). In the present study, mesoporous silica nanoparticles (MSNs) were used as a biocompatible drug delivery system, which could increase the solubility of water-soluble drugs, enhance their bioavailability and reduce toxicity of normal tissues (4,26,27).…”

“…Anaplastic thyroid carcinoma (ATC) is one of the most aggressive endocrine neoplasms, which has a high mortality rate despite the fact that ATC only accounts for 2% of all thyroid cancers (1). The median survival period of patients with ATC is less than half a year, and the 1-year survival rate is less than 20% after diagnosis (2)(3)(4). However, many patients spend money and ultimately succumb to ATC due to dismal prognosis, incurability, side effects, and complexity of treatment (5).…”

Multimodal Decorations of Mesoporous Silica Nanoparticles for Improved Cancer Therapy

“…The same group has also demonstrated delivery of the MSN encapsulating the anti-cancer drug, sunitinib in a significantly higher amount to the U87MG tumor by targeting VEGFR exploiting VEGF 121 ligand in comparison with the non-targeted delivery [ 119 ]. Moreover, Zhang et al have shown increased targeting ability and retention time of anti-VEGFR2 targeted MSN in anaplastic thyroid cancer tumor-bearing mouse [ 120 ]. Bevacizumab or related antibodies have been also exploited for targeting VEGF receptors.…”