Effects of selenium on antioxidant enzyme activity and bioaccessibility of arsenic in arsenic-stressed radish.

Consuming arsenic (As)-contaminated vegetables is the main route of As exposure in humans. The present study focused on the alterations in antioxidant enzymatic activities and As bioaccessibility in As-contaminated radish subjected to Se. Compared to the CK group, the total As content in raw radish was reduced by 27.5 ± 1.3%, and the bioaccessibility of As was reduced by 21.9 ± 2.3% in the 6 mg Se kg-1 treatment group. The total As content in the treatment groups decreased first but then increased with increasing Se application in raw radish, gastric (G) fraction and gastrointestinal (GI) fraction, while the antioxidant activity exhibited the opposite trend. The results revealed that a low amount of Se effectively blocks the accumulation of As in radish, improves the antioxidant activity in radish and reduces the bioaccessibility of As. These findings provide new ideas for effectively alleviating the spread of As to the human body through the food chain.

Assessing bioaccessibility of Se and I in dual biofortified radish seedlings using simulated in vitro digestion.

Selenium (Se) and iodine (I) are essential elements for humans, and biofortification of vegetables with these elements is an effective way to amend their deficiencies in the diet. In this study, the distribution and transformation of Se and I species were investigated in radish seedlings that were simultaneously supplemented with these two elements; the fate and the bioaccessibility of Se and I species were dynamically surveyed in the oral, gastric and intestinal phases using a simulated in vitro digestion method. The radish seedlings were cultivated in hydroponic conditions with Se (IV), Se (VI), I- and IO3- (each 1 mg L-1). The results revealed that Se-methylselenocysteine (MeSeCys), selenocystine (SeCys2), selenomethionine (SeMet) and Se (VI) were present in radish, and MeSeCys was the dominant species in both gastric and intestinal extracts, comprising 32.7 ±â€¯1.5% and 39.6 ±â€¯1.1% of the total content, respectively. I- was also the dominant species, which accounted for 57.1 ±â€¯2.1%, 46.6 ±â€¯1.5% and 68.8 ±â€¯1.8% of the total digested content respectively in the oral, gastric and intestinal extracts. Meanwhile, IO3- was absent and organic I accounted for approximately 20%. The bioaccessibility of Se and I in the intestinal phase reached 95.5 ±â€¯2.5% and 85.8 ±â€¯0.9%, respectively; although after dialysis through membranes, the data reduced to 60.1 ±â€¯2.8% and 39.6 ±â€¯0.8%, respectively. Contents of MeSeCys and I- increased from the oral to intestinal phase and the bioaccessibility of both Se and I in radish was above 85%. So radish is suitable as a potential dietary source of Se and I with biofortification.

Anti-EGFR Peptide-Conjugated Triangular Gold Nanoplates for Computed Tomography/Photoacoustic Imaging-Guided Photothermal Therapy of Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is difficult to cure because of the high recurrence rate and the side effects of current treatments. It is urgent to develop a new treatment that is safer and more effective than current treatments against NSCLC. Herein, we constructed anti-epidermal growth factor receptor (EGFR) peptide-conjugated PEGylated triangular gold nanoplates (TGN-PEG-P75) as a targeting photothermal therapy (PTT) agent to treat NSCLC under the guidance of computed tomography (CT) and photoacoustic (PA) imaging. The surface of TGNs is successfully conjugated with a novel peptide P75 that has the specific affinity to epidermal growth factor receptor (EGFR). It is found that the EGFR is overexpressed in NSCLC cells. The TGN-PEG-P75 has uniform edge length (77.9 ± 7.0 nm) and neutrally charged surface. The cell uptake experiments demonstrate remarkable affinity of the TGN-PEG-P75 to high EGFR expression cells than low EGFR expression cells (5.1-fold). Thanks to the strong near-infrared absorbance, high photothermal conversion efficiency, and the increased accumulation in tumor cells via the interaction of P75 and EGFR, TGN-PEG-P75 exhibits 3.8-fold superior therapeutic efficacy on HCC827 cells than TGN-PEG. The in vivo CT/PA dual-modal imaging of the TGN-PEG-P75 is helpful in selecting the optimal treatment time and providing real-time visual guidance of PTT. Furthermore, treatments on HCC827 tumor-bearing mouse model demonstrate that the growth of NSCLC cells can be effectively inhibited by the TGN-PEG-P75 through PTT, indicating the great promise of the nanoplatform for treating NSCLC in vivo.

Adjuvant Photothermal Therapy Inhibits Local Recurrences after Breast-Conserving Surgery with Little Skin Damage.

Adjuvant treatments following breast-conserving surgery (BCS) are essential to reduce the risk of local recurrences in patients with breast cancer. However, current adjuvant treatments are based on ionizing radiation, which brings radiation-induced damage and amplifies the risk of death. Here we explore the feasibility of using non-ionizing light to induce photothermal therapy as an adjuvant treatment to BCS. In an orthotopic breast cancer mice model, we demonstrate that adjuvant photothermal therapy (aPTT) decreases the incidence of local recurrences after BCS with no expense of cosmetic outcome. In comparison with conventional photothermal therapy, the technique used in aPTT provides more uniformly distributed light energy and less risk of skin burns and local recurrences. Overall, this work represents a departure from the traditional concept of using PTT as an alternative to surgery and reveals the potential of using PTT as an alternative to adjuvant radiation therapy, which is valuable especially for patients susceptible to radiation damage.

Timely coordinated phototherapy mediated by mesoporous organosilica coated triangular gold nanoprisms.

A variety of nanocarriers have been designed to deliver photosensitizers (PSs) and promote the clinical applications of photodynamic therapy (PDT). However, most of them suffer from insufficient loading capability, premature leakage, and/or unstable therapeutic efficacy. Herein, we constructed a novel nanocomposite (TGP@MOS) with a benzene-bridged mesoporous organosilica shell and a triangular gold nanoprism core. The TGP@MOS could load model PS molecules, zinc phthalocyanine (ZnPc), with high loading capacity (11.8 wt%) and minimal premature leakage (only 2.6% after incubation in PBS with 10% FBS for 60 h) viaπ-π stacking interactions and hydrophobic interactions. We demonstrated that the obtained TGP@MOS-ZnPc could realize timely coordinated photodynamic/photothermal therapy upon single irradiation, and thus stabilize and maximize the therapeutic efficacy of phototherapy both in vitro and in vivo. Other advantages of TGP@MOS-ZnPc include excellent water solubility, stability, hemocompatibility and biocompatibility.

Photosensitizer-loaded biomimetic platform for multimodal imaging-guided synergistic phototherapy.

Photodynamic therapy (PDT) has attracted much attention as a strategy for tumor therapy. However, the insolubility and poor tumor-targeting ability of most photosensitizers (PSs) hinder PDT from further development. Therefore, it is necessary to explore new carriers with good water solubility and biocompatibility to deliver PSs to tumors. Melanin nanoparticles are novel biomimetic nanocarriers with excellent biocompatibility, loading capacity, photothermal therapy (PTT) and magnetic resonance (MR)/photoacoustic (PA) imaging properties. Here we designed polydopamine melanin nanoparticles (PDMNs) as a delivery platform for the photosensitizer Chlorin e6 (PDMN-Ce6) and realized its application as a theranostic agent for tumor therapy. The PDMN-Ce6 exhibited excellent biocompatibility, good water solubility and high loading capability (35.2 wt%) for Ce6. Compared with the free Ce6, PDMN-Ce6 showed higher cellular internalization and superior synergistic phototherapy effects in an in vitro study. An in vivo study indicated that the accumulation of PDMN-Ce6 at tumor sites was 2.8-fold higher than that of free Ce6 at 24 h post-injection, which was beneficial for MR/PA imaging. Moreover, the synergetic therapy significantly inhibited tumor growth, causing tumor necrosis and tumor angiogenesis suppression. These results suggest that our biomimetic and biocompatible platform could improve the delivery of Ce6 to tumors and realize multimodal imaging-guided tumor synergetic phototherapy.

Tri-stimuli-responsive biodegradable theranostics for mild hyperthermia enhanced chemotherapy.

The combination of hyperthermia and chemotherapy is able to greatly enhance the treatment efficacy mainly due to the synergistic interactions between these two treatments. In this study, we propose a new concept of mild hyperthermia enhanced chemotherapy to explore and validate the synergistic mechanism in vitro and in vivo. To do this, a novel kind of biodegradable nanotheranostics based on copper sulfide doped periodic mesoporous organosilica nanoparticles (CuS@PMOs) was constructed via an in situ growth method for light-triggered mild hyperthermia and drug delivery. The as-prepared CuS@PMOs exhibit a high doxorubicin (DOX) loading capacity of 470 mg/g. The DOX release from CuS@PMOs can be precisely controlled by three stimuli, including intracellular glutathione (GSH), acidic environment in tumor cells, and external laser irradiation. Most intriguingly, mild hyperthermia induced by laser-irradiated CuS nanoparticles can dramatically improve the cell uptake of nanotheranostics both in vitro and in vivo, thus significantly enhancing the chemotherapeutic efficacy for complete tumor growth suppression without recurrence. Meanwhile, the fluorescence recovery following the DOX release can be used as an indicator to monitor the chemotherapeutic progress.

Gold nanorod embedded large-pore mesoporous organosilica nanospheres for gene and photothermal cooperative therapy of triple negative breast cancer.

To date, clinicians still lack an effective strategy to treat triple negative breast cancer (TNBC). In this work, we design for the first time a gold nanorod embedded large-pore mesoporous organosilica (GNR@LPMO) nanoplatform for gene and photothermal cooperative therapy of TNBC. The synthesized GNR@LPMOs possess a uniform size (175 nm), high surface area (631 m2 g-1), large pore size, excellent photothermal efficiency, and good biocompatibility. Thanks to the large-pore mesoporous organosilica layer, the GNR@LPMO nanoplatforms display much higher loading capacity of siRNA compared with traditional liposome and bare gold nanorods. Thus, functional siRNA can be efficiently delivered into TNBC cells by GNR@LPMOs, causing much higher cell apoptosis through knocking down the PLK1 proteins. By combining the effective gene delivery and photothermal abilities, the GNR@LPMO nanoplatforms are further used for gene and photothermal cooperative therapy of TNBC, which induce a 15 fold higher mice tumor inhibition rate than sole therapy modality, indicating the potential clinical use of this novel nanoplatform in treating TNBC.