Surface-Functionalized Modified Copper Sulfide Nanoparticles Enhance Checkpoint Blockade Tumor Immunotherapy by Photothermal Therapy and Antigen Capturing.

Nanomaterial-based tumor photothermal therapy (PTT) has attracted increasing attention and been a promising method for cancer treatment because of its low level of adverse effects and noninvasiveness. However, thermotherapy alone still cannot control tumor metastasis and recurrence. Here, we developed surface-functionalized modified copper sulfide nanoparticles (CuS NPs). CuS NPs can not only be used as photothermal mediators for tumor hyperthermia but can adsorb tumor antigens released during hyperthermia as an antigen-capturing agent to induce antitumor immune response. We selected maleimide polyethylene glycol-modified CuS NPs (CuS NPs-PEG-Mal) with stronger antigen adsorption capacity, in combination with an immune checkpoint blocker (anti-PD-L1) to evaluate the effect of hyperthermia, improving immunotherapy in a 4T1 breast cancer tumor model. The results showed that hyperthermia based on CuS NPs-PEG-Mal distinctly increased the levels of inflammatory cytokines in the serum, leading to a tumor immunogenic microenvironment. In cooperation with anti-PD-L1, PTT mediated by CuS NPs-PEG-Mal enhanced the number of tumor-infiltrating CD8+ T cells and inhibited the growth in primary and distant tumor sites of the 4T1 tumor model. The therapeutic strategies provide a simple and effective treatment option for metastatic and recurrent tumors.

Renal Clearable Ag Nanodots for in Vivo Computer Tomography Imaging and Photothermal Therapy.

Albumin-stabilized Ag nanodots (ANDs) are prepared by a one-step biomineralization method. The highly crystallized nanodots have ultrasmall sizes (approximately 5.8 nm) and robust X-ray attenuation (5.7313 HU per mM Ag). The unlabeled ANDs are directly excreted from the body via the urine after in vivo X-ray computer tomography (CT) imaging application. ANDs could be used as CT imaging agents and effective photothermal therapy agents. Tumor growth inhibition reaches 90.2% after photothermal treatment with ANDs. ANDs are promising tools for in vivo CT imaging and clearable near-infrared-triggered theranostic agents.

Plasmon-mediated generation of reactive oxygen species from near-infrared light excited gold nanocages for photodynamic therapy in vitro.

We have performed fundamental assays of gold nanocages (AuNCs) as intrinsic inorganic photosensitizers mediating generation of reactive oxygen species (ROS) by plasmon-enabled photochemistry under near-infrared (NIR) one/two-photon irradiation. We disclosed that NIR light excited hot electrons transform into either ROS or hyperthermia. Electron spin resonance spectroscopy was applied to demonstrate the production of three main radical species, namely, singlet oxygen ((1)O2), superoxide radical anion (O2(-•)), and hydroxyl radical ((•)OH). The existence of hot electrons from irradiated AuNCs was confirmed by a well-designed photoelectrochemical experiment based on a three-electrode system. It could be speculated that surface plasmons excited in AuNCs first decay into hot electrons, and then the generated hot electrons sensitize oxygen to form ROS through energy and electron transfer modes. We also compared AuNCs' ROS generation efficiency in different surface chemical environments under one/two-photon irradiation and verified that, compared with one-photon irradiation, two-photon irradiation could bring about much more ROS. Furthermore, in vitro, under two-photon irradiation, ROS can trigger mitochondrial depolarization and caspase protein up-regulation to initiate tumor cell apoptosis. Meanwhile, hyperthermia mainly induces tumor cell necrosis. Our findings suggest that plasmon-mediated ROS and hyperthermia can be facilely regulated for optimized anticancer phototherapy.

Cytotoxicity and therapeutic effect of irinotecan combined with selenium nanoparticles.

Although chemotherapeutic drugs are widely applied for clinic tumor treatment, severe toxicity restricts their therapeutic efficacy. In this study, we reported a new form of selenium, selenium nanoparticles (Nano Se) which have significant lower toxicity and acceptable bioavailability. We investigated Nano Se as chemotherapy preventive agent to protect against toxicities of anticancer drug irinotecan and synergistically enhance the anti-tumor treatment effect in vitro and in vivo. The underlying mechanisms were also investigated. The combination of Nano Se and irinotecan showed increased cytotoxic effect with HCT-8 tumor cells likely by p53 mediated apoptosis. Nano Se inhibited growth of HCT-8 tumor cells partially through caspases mediated apoptosis. In vivo experiment showed Nano Se at a dose of 4 mg/kg/day significantly alleviated adverse effects induced by irinotecan (60 mg/kg) treatment. Nano Se alone treatment did not induce any toxic manifestations. The combination of Nano Se and irinotecan dramatically inhibited tumor growth and significantly induced apoptosis of tumor cells in HCT-8 cells xenografted tumor. Tumor inhibition rate was about 17.2%, 48.6% and 62.1% for Nano Se, irinotecan and the combination of Nano Se and irinotecan, respectively. The beneficial effects of Nano Se for tumor therapy were mainly ascribed to selectively regulating Nrf2-ARE (antioxidant responsive elements) pathway in tumor tissues and normal tissues. Our results suggest Nano Se is a promising selenium species with potential application in cancer treatment.

The suppression of prostate LNCaP cancer cells growth by Selenium nanoparticles through Akt/Mdm2/AR controlled apoptosis.

The trace element Selenium is suggested having cancer prevention activity and used as food supplement. Previous results had shown Selenium nanoparticles are safer compared with other Selenium compounds like selenomethionine, sodium selenite and monomethylated Selenium, however, its anticancer activity and intrinsic mechanisms are still elusive. Here, we prepared Selenium nanoparticles and investigated its inherent anticancer mechanisms. We found Selenium nanoparticles inhibit growth of prostate LNCaP cancer cells partially through caspases mediated apoptosis. Selenium nanoparticles suppress transcriptional activity of androgen receptor via down-regulating its mRNA and protein expression. Moreover, Selenium nanoparticles activate Akt kinase by increasing its phosphorylation, promote Akt-dependent androgen receptor phosphorylation and Mdm2 regulated degradation through proteasome pathway. We suggest Selenium nanoparticles suppress prostate cancer cells growth by disrupting androgen receptor, implicating a potential application in cancer treatment.