A superparamagnetic graphene oxide -Fe 3 O 4 nanoparticles hybrid (GO-Fe 3 O 4 ) was prepared via a simple and effective chemical precipitation method. The amount of loading of Fe 3 O 4 on GO was estimated as 18.6 wt% by atomic absorption spectrometry. The hybrid was then loaded with doxorubicin hydrochloride (DXR) and the loading capacity was as high as 1.08 mg mg À1 . Both of the GO-Fe 3 O 4 hybrids before and after loading with DXR can be dispersed well in aqueous solution. They can congregate under acidic conditions and move regularly under the force of an external magnet. Furthermore, the aggregated hybrid can be redispersed to form a stable suspension under basic conditions. These properties make it a potential candidate for controlled targeted drug delivery and release.

A dual-targeting drug delivery and pH-sensitive controlled release system based on multifunctionalized graphene oxide (GO) was established in order to enhance the effect of targeted drug delivery and realize intelligently controlled release. A superparamagnetic GO-Fe 3 O 4 nanohybrid was firstly prepared via a simple and effective chemical precipitation method. Then folic acid, a targeting agent toward some tumor cells, was conjugated onto Fe 3 O 4 nanoparticles via the chemical linkage with amino groups of the 3-aminopropyl triethoxysilane (APS) modified superparamagnetic GO-Fe 3 O 4 nanohybrid, to give the multi-functionalized GO. Doxorubicin hydrochloride (Dox) as an anti-tumor drug model was loaded onto the surface of this multi-functionalized GO via p-p stacking. The drug loading capacity of this multi-functionalized GO is as high as 0.387 mg mg À1 and the drug release depends strongly on pH values. Cell uptake studies were carried out using fluorescein isothiocyanate labeled or Dox loaded multi-functionalized GO to evaluate their targeted delivery property and toxicity to tumor cells. The results show that this multi-functionalized GO has potential applications for targeted delivery and the controlled release of anticancer drugs.

Sonodynamic therapy (SDT) is an emerging approach that involves a combination of low-intensity ultrasound and specialized chemical agents known as sonosensitizers. Ultrasound can penetrate deeply into tissues and can be focused into a small region of a tumor to activate a sonosensitizer which offers the possibility of non-invasively eradicating solid tumors in a site-directed manner. In this article, we critically reviewed the currently accepted mechanisms of sonodynamic action and summarized the classification of sonosensitizers. At the same time, the breath of evidence from SDT-based studies suggests that SDT is promising for cancer treatment.

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Metastasis is one of the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Immunotherapy brings hope and opportunity to solve this challenge, while its clinical applications are greatly inhibited by the tumor immunosuppressive environment. Here, an intelligent biomimetic nanoplatform was designed based on dendritic large-pore mesoporous silica nanoparticles (DLMSNs) for suppressing metastatic TNBC by combining photothermal ablation and immune remodeling. Taking advantage of the ordered large-pore structure and easily chemically modified property of DLMSNs, the copper sulfide (CuS) nanoparticles with high photothermal conversion efficiency were in situ deposited inside the large pores of DLMSNs, and the immune adjuvant resiquimod (R848) was loaded controllably. A homogenous cancer cell membrane was coated on the surfaces of these DLMSNs, followed by conjugation with the anti-PD-1 peptide AUNP-12 through a polyethylene glycol linker with an acid-labile benzoic-imine bond. The thus-obtained AM@DLMSN@CuS/R848 was applied to holistically treat metastatic TNBC in vitro and in vivo. The data showed that AM@DLMSN@CuS/R848 had a high TNBC-targeting ability and induced efficient photothermal ablation on primary TNBC tumors under 980 nm laser irradiation. Tumor antigens thus generated and increasingly released R848 by response to the photothermal effect, combined with AUNP-12 detached from AM@DLMSN@CuS/R848 in the weakly acidic tumor microenvironment, synergistically exerted tumor vaccination, and T lymphocyte activation functions on immune remodeling to prevent TNBC recurrence and metastasis. Taken together, this study provides an intelligent biomimetic nanoplatform to enhance therapeutic outcomes in metastatic TNBC.

Graphene oxide (GO) has attracted enormous interests due to its extraordinary properties. Recent studies have confirmed the cytotoxicity of GO, we further investigate its mutagenic potential in this study. The results showed that GO interfered with DNA replication and induced mutagenesis at molecular level. GO treatments at concentrations of 10 and 100 mg/mL altered gene expression patterns at cellular level, and 101 differentially expressed genes mediated DNA-damage control, cell apoptosis, cell cycle, and metabolism. Intravenous injection of GO at 4 mg/kg for 5 consecutive days clearly induced formation of micronucleated polychromic erythrocytes in mice, and its mutagenesis potential appeared to be comparable to cyclophosphamide, a classic mutagen. In conclusion, GO can induce mutagenesis both in vitro and in vivo, thus extra consideration is required for its biomedical applications. G raphene, firstly isolated from graphite in 2004 1 , is a flat monolayer of carbon atoms tightly packed into a two-dimensional (2D) honeycomb lattice. Due to the unique physicochemical properties, high surface area, excellent thermal conductivity, electric conductivity, and strong mechanical strength, graphene and graphene oxide (GO) have shown great promise in many applications, such as electronics, energy storage and conversion, mechanics, and biotechnologies [2][3][4][5][6] . Recently, many studies reported that GO has outstanding potentials in the field of biomedicine. GO and PEGylated GO exhibit certain advantages in vitro and in vivo drug delivery, such as high drug loading efficiency, controlled drug release, tumor-targeting drug delivery, and reversal effect against cancer drug resistance [7][8][9][10] . In addition, GO has strong optical absorbance in the near-infrared (NIR) region, thus is suitable for the photothermal therapy [11][12][13] . Now, it is possible to manufacture high-quality GO in large scale quantities 14,15 , and its industry production is increasing exponentially. Together with its potential applications in the biomedical field, the biosafety of GO is of critical importance. Many investigations have paid attentions to its biocompatibilty [16][17][18][19] . At a concentration approximate to 50 mg/mL or higher, GO begins to show the toxicity against erythrocytes, fibroblasts, and PC12 cells. It can induce cell apoptosis, hemolysis, and oxidative stress 16,18,19 . Surface chemical modification, such as PEGylation, is likely to improve the biocompatibility of GO 20,21 . However, the chemical bonds linking GO with modified polymer can be broken down in vivo, thus surface-modified GO can also induce in vivo toxicity.Several investigations have reported that treatments with carbon nanomaterials, such as nanodiamonds and multiwalled carbon nanotubes, can elevate the expression of p53, MOGG-1, and Rad51, which reflect the chromosomal DNA damage 22,23 . However, it is not clear whether this DNA damage induced by carbon nanomaterials can cause mutagenesis. GO, due to its unique nanosheet structure, can interact wi...

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