Sha-Sha Song

Ultrasmall Au(10-12)(SG)(10-12) nanomolecules for high tumor specificity and cancer radiotherapy.

Radiosensitizers can increase local treatment efficacy under a relatively low and safe radiation dose, thereby facilitating tumor eradication and minimizing side effects. Here, a new class of radiosensitizers is reported, which contain several gold (Au) atoms embedded inside a peptide shell (e.g., Au10-12 (SG)10-12 ) and can achieve ultrahigh tumor uptake (10.86 SUV at 24 h post injection) and targeting specificity, efficient renal clearance, and high radiotherapy enhancement.

Enhanced Tumor Accumulation of Sub‐2 nm Gold Nanoclusters for Cancer Radiation Therapy

A new type of metabolizable and efficient radiosensitizers for cancer radiotherapy is presented by combining ultrasmall Au nanoclusters (NCs, <2 nm) with biocompatible coating ligands (glutathione, GSH). The new nanoconstruct (GSH-coated Au25 NCs) inherits attractive features of both the Au core (strong radiosensitizing effect) and GSH shell (good biocompatibility). It can preferentially accumulate in tumor via the improved EPR effect, which leads to strong enhancement for cancer radiotherapy. After the treatment, the small-sized GSH-Au25 NCs can be efficiently cleared by the kidney, minimizing any potential side effects due to the accumulation of Au25 NCs in the body.

Metabolizable Bi2Se3 Nanoplates: Biodistribution, Toxicity, and Uses for Cancer Radiation Therapy and Imaging

Bi, a high atomic number element, has a high photoelectric absorption coefficient, and Se has anticancer activity. Hence, their compound chalcogenide (Bi2Se3) deserves a thorough investigation for biomedical applications. This study reveals that Bi2Se3 nanoplates (54 nm wide) protected with poly(vinylpyrollidone) (PVP) could be presumed to have low toxicity even at a high dose of 20 mg/kg in mice. This conclusion is made through studies on the biodistribution and 90-day long term in vivo clearance of the nanoplates. The liver and spleen are dominant organs for accumulation of the nanoplates, which is mainly due to RES absorption. 93% of the nanoplates are cleared after 90 days of treatment. Concentrations of Bi and Se in tumor tissue continuously increased until 72 h after intraperitoneal injection into mice. Such selective accumulation of Bi is utilized to enhance the contrast of X-ray computerized tomography (CT) images. Bi element concentrated in a tumor leads to damage on the tumor cells when exposed to gamma radiation. Growth of the tumor is significantly delayed and stopped in 16 days after the tumor is treated by radiation with Bi2Se3 nanoplates. This work clearly shows that Bi2Se3 nanoplates may be used for cancer radiation therapy and CT imaging. The nanoplates deserve further study for biological and medical applications.

Ultrasmall Glutathione-Protected Gold Nanoclusters as Next Generation Radiotherapy Sensitizers with High Tumor Uptake and High Renal Clearance

Radiotherapy is often the most straightforward first line cancer treatment for solid tumors. While it is highly effective against tumors, there is also collateral damage to healthy proximal tissues especially with high doses. The use of radiosensitizers is an effective way to boost the killing efficacy of radiotherapy against the tumor while drastically limiting the received dose and reducing the possible damage to normal tissues. Here, we report the design and application of a good radiosensitizer by using ultrasmall Au29–43(SG)27–37 nanoclusters (<2 nm) with a naturally-occurring peptide (e.g., glutathione or GSH) as the protecting shell. The GSH-coated Au29–43(SG)27–37 nanoclusters can escape the RES absorption, leading to a good tumor uptake (~8.1% ID/g at 24 h post injection). As a result, the as-designed Au nanoclusters led to a strong enhancement for radiotherapy, as well as a negligible damage to normal tissues. After the treatment, the ultrasmall Au29–43(SG)27–37 nanoclusters can be efficiently cleared by the kidney, thereby avoiding potential long-term side-effects caused by the accumulation of gold atoms in the body. Our data suggest that the ultrasmall peptide-protected Au nanoclusters are a promising radiosensitizer for cancer radiotherapy.

Sex differences in the toxicity of polyethylene glycol-coated gold nanoparticles in mice

Gold nanoparticles have received wide interest in disease diagnosis and therapy, but one of the important issues is their toxicological effects in vivo. Sex differences in the toxicity of gold nanoparticles are not clear. In this work, body weight, organ weight, hematology, and biochemistry were used to evaluate sex differences in immune response and liver and kidney damage. Pathology was used to observe the general toxicity of reproductive organs. The immune response was influenced significantly in female mice, with obvious changes in spleen and thymus index. Hematology results showed that male mice treated with 22.5 nm gold nanoparticles received more significant infection and inflammation than female mice. Meanwhile, the biochemistry results showed that 4.4 and 22.5 nm gold nanoparticles caused more significant liver damage in male mice than female mice, while 22.5, 29.3, and 36.1 nm gold nanoparticles caused more significant kidney damage in female mice than male mice. No significant toxicological response was found in the reproductive system for female or male mice. It was found that gold nanoparticles caused more serious liver toxicity and infection in male mice than female mice. These findings indicated that sex differences may be one of the important elements for in vivo toxicity of gold nanoparticles.

Passing through the renal clearance barrier: toward ultrasmall sizes with stable ligands for potential clinical applications

The use of nanoparticles holds promise for medical applications, such as X-ray imaging, photothermal therapy and radiotherapy. However, the in vivo toxicity of inorganic nanoparticles raises some concern regarding undesirable side effects which prevent their further medical application. Ultrasmall sub-5.5 nm particles can pass through the barrier for renal clearance, minimizing their toxicity. In this letter we address some recent interesting work regarding in vivo toxicity and renal clearance, and discuss the possible strategy of utilizing ultrasmall nanomaterials. We propose that small hydrodynamic sized nanoclusters can achieve both nontoxic and therapeutic clinical features.

Two dimensional TiO2 nanosheets: in vivo toxicity investigation

Titanium dioxide (TiO2) nanosheets have received attention for photodynamic therapy due to their unique electronic structure and high surface activity. However, the biological response and toxicity of two dimensional (2D) nanomaterials are still not clear. Herein, in vivo toxicity of TiO2 nanosheets, such as biodistribution, hematology, biochemistry and pathology, were evaluated at the dose of 10 mg kg−1 by intraperitoneal injection for up to 30 days. It was found that TiO2 could gradually accumulate in the liver and spleen with increase of exposure time, which is due to large size induced absorption from the reticuloendothelial system (RES). Furthermore, the hematological data indicated that no significant difference was found. However, the biochemistry showed that the liver indicator, AST, presented a significant difference after 30 days compared with control mice. The present work revealed that 2D TiO2 nanosheets did not cause appreciable toxicity, but induced accumulation in the liver and slight abnormality of the liver with increasing exposure time.

Catalytic topological insulator Bi2Se3 nanoparticles for in vivo protection against ionizing radiation

Bi2Se3 nanoparticles (NPs) have attracted wide interests in biological and medical applications. Layer-like Bi2Se3 with high active surface area is promising for free radical scavenging. Here, we extended the medical applications of Bi2Se3 NPs further to in vivo protection against ionizing radiation based on their superior antioxidant activities and electrocatalytic properties. It was found that Bi2Se3 NPs can significantly increase the surviving fraction of mice after exposure of high-energy radiation of gamma ray. Additionally, the Bi2Se3 NPs can help to recover radiation-lowered red blood cell counts, white blood cell counts and platelet levels. Further investigations revealed that Bi2Se3 NPs behaved as functional free radical scavengers and significantly decreased the level of methylenedioxyamphetamine. In vivo toxicity studies showed that Bi2Se3 NPs did not cause significant side effects in panels of blood chemistry, clinical biochemistry and pathology.

Use of epidermal growth factor receptor antibody–gold cluster conjugates with good renal excretion in targeted cancer radiation treatment

Ultra-small gold clusters have been shown to have great potential in biomedical applications; however, it is crucial that the targeting clusters can be rapidly excreted from the body. We prepared epidermal growth factor receptor (EGFR) antibody-gold cluster conjugates with tumour-specific targeting, which also enhanced the effects of therapeutic radiation and had good renal clearance properties. We systematically investigated the effects of these clusters on targeted radiation treatment, renal clearance and toxicity over a period of 25 days in mice. The as-prepared EGFR antibody-gold cluster conjugates showed higher in vitro uptakes than gold clusters alone in treated HeLa cells and resulted in enhanced cancer radiation treatment compared with non-specific gold clusters. The in vivo treatment and improved tumour uptake showed that the EGFR antibody-gold cluster conjugates could result in higher tumour uptake and higher tumour ablation. The EGFR antibody-gold cluster conjugates showed 43% excretion in urine after 24 h, only slightly lower than that of the pure gold clusters (52%). Haematological and biochemical studies showed that the conjugates did not cause liver or kidney toxicity 30 days after injection. Therefore, the use of targeting EGFR antibody-gold cluster conjugates with low toxicities and good renal excretion can enhance radiation treatment and is promising in a number of medical applications.

Original ArticleCatalytic topological insulator Bi2Se3 nanoparticles for in vivo protection against ionizing radiation

Bi2Se3 nanoparticles (NPs) have attracted wide interests in biological and medical applications. Layer-like Bi2Se3 with high active surface area is promising for free radical scavenging. Here, we extended the medical applications of Bi2Se3 NPs further to in vivo protection against ionizing radiation based on their superior antioxidant activities and electrocatalytic properties. It was found that Bi2Se3 NPs can significantly increase the surviving fraction of mice after exposure of high-energy radiation of gamma ray. Additionally, the Bi2Se3 NPs can help to recover radiation-lowered red blood cell counts, white blood cell counts and platelet levels. Further investigations revealed that Bi2Se3 NPs behaved as functional free radical scavengers and significantly decreased the level of methylenedioxyamphetamine. In vivo toxicity studies showed that Bi2Se3 NPs did not cause significant side effects in panels of blood chemistry, clinical biochemistry and pathology.