Polyglycerol-Shelled Reduction-Sensitive Polymersome for DM1 Delivery to HER-2-Positive Breast Cancer.

Supramolecular delivery systems with the prolonged circulation, the potential for diverse functionalization, and few toxin-related limitations have been extensively studied. For the present study, we constructed a linear polyglycerol-shelled polymersome attached with the anti-HER-2-antibody trastuzumab. We then covalently loaded the anticancer drug DM1 in the polymersome via dynamic disulfide bonding. The resulted trastuzumab-polymersome-DM1 (Tra-PS-DM1) exhibits a mean size of 95.3 nm and remarkable drug loading efficiency % of 99.3%. In addition to its superior stability, we observed the rapid release of DM1 in a controlled manner under reductive conditions. Compared to the native polymersomes, Tra-PS-DM1 has shown greatly improved cellular uptake and significantly reduced IC50 up to 17-fold among HER-2-positive cancer cells. Moreover, Tra-PS-DM1 demonstrated superb growth inhibition of HER-2-positive tumoroids; specifically, BT474 tumoroids shrunk up to 62% after 12 h treatment. With exceptional stability and targetability, the PG-shelled Tra-PS-DM1 appears as an attractive approach for HER-2-positive tumor treatment.

A nanoflower-like polypyrrole-based cobalt-nickel sulfide hybrid heterostructures with electrons migration to boost overall water splitting.

The development of high-efficiency and cost-effective difunctional electrocatalysts for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are highly attractive to fulfill the practical water electrolysis. Herein, a novel low-cost difunctional cobalt-nickel sulfide (Co3S4/Ni3S2) flower-like heterostructures are purposely loaded on the surface of polypyrrole (PPy) nanosheets on nickel foam (NF) via feasible and efficient electrodeposition and hydrothermal tactics. The unique hierarchical architecture of the PPy nanosheets and strong electron interaction in the Co3S4/Ni3S2 nanohybrid effectively offer sufficient specific surface area and regulate electronic configuration for expediting the electrocatalytic process. The theoretical simulations also provide convincing proof that the interface of the Co3S4/Ni3S2 heterostructures supplies a lower energy pathway for water adsorption and dissociation, and the electrons migration that occurs when heterostructures emerge is probably the root of the result above. Consequently, the as-fabricated Co3S4/Ni3S2@PPy/NF exhibits outstanding electrochemical activity of HER and OER requiring low overpotentials of 63 mV and 207 mV to reach a current density of 10 mA cm-2 in the alkaline electrolyte, respectively. When equipped in a two-electrode electrolyzer, the Co3S4/Ni3S2@PPy/NF electrode couple displays a low voltage of only 1.52 V at 10 mA cm-2, indicating its potential application in the field of the water electrolysis.

Toolbox of Biodegradable Dendritic (Poly glycerol sulfate)-SS-poly(ester) Micelles for Cancer Treatment: Stability, Drug Release, and Tumor Targeting.

In this paper, we present well-defined dPGS-SS-PCL/PLGA/PLA micellar systems demonstrating excellent capabilities as a drug delivery platform in light of high stability and precise in vitro and in vivo drug release combined with active targetability to tumors. These six amphiphilic block copolymers were each targeted in two different molecular weights (8 or 16 kDa) and characterized using 1H NMR, gel permeation chromatography (GPC), and elemental analysis. The block copolymer micelles showed monodispersed size distributions of 81-187 nm, strong negative charges between -52 and -41 mV, and low critical micelle concentrations (CMCs) of up to 1.13-3.58 mg/L (134-527 nM). The serum stability was determined as 94% after 24 h. The drug-loading efficiency for Sunitinib ranges from 38 to 83% (8-17 wt %). The release was selectively triggered by glutathione (GSH) and lipase, reaching 85% after 5 days, while only 20% leaching was observed under physiological conditions. Both the in vitro and in vivo studies showed sustained release of Sunitinib over 1 week. CCK-8 assays on HeLa lines demonstrated the high cell compatibility (1 mg/mL, 94% cell viability, 48 h) and the high cancer cell toxicity of Sunitinib-loaded micelles (IC50 2.5 µg/mL). By in vivo fluorescence imaging studies on HT-29 tumor-bearing mice, the targetability of dPGS7.8-SS-PCL7.8 enabled substantial accumulation in tumor tissue compared to nonsulfated dPG3.9-SS-PCL7.8. As a proof of concept, Sunitinib-loaded dPGS-SS-poly(ester) micelles improved the antitumor efficacy of the chemotherapeutic. A tenfold lower dosage of loaded Sunitinib led to an even higher tumor growth inhibition compared to the free drug, as demonstrated in a HeLa human cervical tumor-bearing mice model. No toxicity for the organism was observed, confirming the good biocompatibility of the system.

[Preoperative hyperfractionated accelerated irradiation-induced apoptosis in non-small cell lung cancer].

BACKGROUND: To study the apoptosis inducing effect of preoperative hyperfractionated accelerated radiation therapy (HART) and expression of Bcl-2, Bax proteins in non-small cell lung cancer. METHODS: From October 1999 to March 2001, 81 patients with non-small cell lung cancer were prospectively divided into preoperative HART group (20 patients) and surgical group (61 patients). The patients in preoperative HART group were given preoperative irradiation with 2.5 Gy/fraction, twice a day to a total dose of 25 Gy/10 fractions/5-7 days using anterior-posterior opposing parallel fields, then operation would be performed within 2 weeks. The patients in surgical group only received surgical treatment. Apoptotic index (AI), cell cycle distribution and expression of Bcl-2, Bax proteins were quantitatively analyzed by indirect-immunofluorescene and flow cytometry. RESULTS: AI was 4.6%±2.3% in surgical group and 12.8%±4.3% in preoperative HART group, respectively ( P < 0.001). There was no difference in S phase fraction (SPF) between the two groups ( P > 0.05). The fluorescence index (FI) for Bcl-2, Bax proteins and the ratio of Bcl-2/Bax were 1.33±0.21, 1.05±0.13 and 1.29±0.23 in surgical group, and 1.14±0.26, 1.19±0.16 and 0.96±0.23 in preoperative HART group respectively ( P < 0.01, P < 0.001 and P < 0.001 respectively). AI showed a positive correlation to Bax protein ( P < 0.001) and a negative correlation to the ratio of Bcl-2/Bax ( P < 0.01). CONCLUSIONS: Preoperative HART may induce a high-level apoptosis by decreasing the expression of Bcl-2 protein and increasing the expression of Bax protein. However, it is still necessary to further observe whether it can improve the long-term survival of patients with NSCLC.