Use of copper-cysteamine nanoparticles to simultaneously enable radiotherapy, oxidative therapy and immunotherapy for melanoma treatment

Abstract

Dear Editor, Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) are three major types of skin cancer. Among them, melanoma is the most severe form and accounts for~4% of all newly diagnosed cancers annually in the United States. It is estimated that approximately 9500 people are diagnosed with skin cancer every day, and more than 1 million Americans are living with melanoma. Melanoma treatment is still a major challenge in the clinic. Photodynamic therapy (PDT) is composed of targeted ablation and immune activation, is less invasive than other therapies and has been widely used in the treatment of various cancers. However, the limitation of light penetration is an issue in PDT for deep cancer treatment. 1 To overcome this limitation and enable PDT for deep cancer treatment, researchers have proposed X-ray-induced PDT 1 and nanoparticle self-lighting PDT, 2 and these techniques have become intensively studied topics. Recently, Chen et al. 3 invented a new sensitizer called copper-cysteamine (Cu-Cy) that can be activated by UV, 4 X-rays, 5 microwave, 6 and ultrasound 7 to generate reactive oxygen species (ROS) to destroy cancer cells as well as bacteria. 8 As ROS generation by Cu-Cy nanoparticles (NPs) is not solely activated by regular light, it is more appropriate to call it oxidative therapy (OT) rather than PDT. Cu-Cy NPs of an average size of 96 nm have been tested for skin cancer treatment. 9 It was found that these Cu-Cy NP-based X-PDT exhibited a strong antitumor effect towards SCC. However, B16F10 melanoma was resistant to these Cu-Cy NP-based X-PDT, both in vitro and in vivo. 9 Size is known to be a sensitive factor influencing nanomaterial properties and performance. To further evaluate the effect of Cu-Cy NP-based X-PDT on melanoma, we applied particles with an average size of~40 nm for the treatment of melanoma, as the 40 nm Cu-Cy NPs have a larger surface area than other NPs, thereby producing more ROS. 10 In addition, the cell uptake is higher for the 40 nm NPs. As expected, the 40 nm Cu-Cy NPs were very effective in inhibiting melanoma under X-ray stimulation. These observations confirmed that the combination of Cu-Cy and X-rays facilitated cell apoptosis and/or necrosis of B16 cells. More interestingly, this combination promoted the formation of the antitumor immune response. These results suggest that Cu-Cy NPs can simultaneously facilitate radiotherapy, oxidative therapy, and immunotherapy for melanoma treatment, as illustrated in Fig. 1a. The distribution of Cu-Cy was assessed by confocal fluorescence microscopy. As shown in Supplementary Fig. S1, the uptake of Cu-Cy NPs in the nucleus after 6 h was substantially increased compared to that after 2 and 4 h of incubation. Next, the cytotoxicity was measured to assess the efficacy of Cu-Cy on B16 cells by the CCK8 viability assay. After incubation with various amounts of Cu-Cy for 24 h, the cells were irradiated with X-rays at

A polymer–lipid membrane artificial cell nanocarrier containing enzyme–oxygen biotherapeutic inhibits the growth of B16F10 melanoma in 3D culture and in a mouse model

“…Indeed, in our 2D study, we find that the polyhaemoglobin component of polylactide nanocarrier-polyhaemoglobin increases ROS production [16,17]. Others had also shown that ROS inhibits tumour growth [18]. Our 3D culture studies (Figure 6) also showed that polylactide nanocarrier-polyhaemoglobin has some effect on melanoma cells though not as much as the polylactide nanocarrier-PH-TYR.…”

Effects of Nanoparticle Size and Radiation Energy on Copper-Cysteamine Nanoparticles for X-ray Induced Photodynamic Therapy

“…It was found that these Cu-Cy nanoparticle-based X-PDT exhibited a remarkable antitumor effect towards SCC. However, B16F10 melanoma was resistant to these Cu-Cy nanoparticle based X-PDT, both in vitro and in vivo [49], whereas the 40 nm Cu-Cy nanoparticles are very effective in inhibiting melanoma under X-ray stimulation [50]. This could be due to the fact that the 40 nm Cu-Cy nanoparticles have a larger surface area, thereby producing more ROS and the cellular uptake is higher for the 40 nm nanoparticles [18].…”

Recent Advances in Nanotechnology for the Treatment of Melanoma

“…Also the induction of adequate immune responses after photo tumor ablation may be fundamental to obtain a long term therapeutic effect of phototherapy. For this reason, Zhu et al projected the photosensitizer chlorin e6 (Ce6) and the well-known immunoadjuvant aluminum hydroxide into bovine serum albumin by biomineralization as a novel nanosystem (Al-BSA-Ce6 NPs) [ 92 ]. After intravenous injection, the nanoparticles were able to destroy tumor cells effectively and, at the same time protect animals against tumor rechallenge and metastasis by strongly inducing a systemic anti-tumor immune response.…”