Engineering folate-targeting diselenide-containing triblock copolymer as a redox-responsive shell-sheddable micelle for antitumor therapy in vivo.

The oxidation-reduction (redox)-responsive micelle system is based on a diselenide-containing triblock copolymer, poly(ε-caprolactone)-bis(diselenide-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate) [PCL-(SeSe-mPEG/PEG-FA)2]. This has helped in the development of tumor-targeted delivery for hydrophobic anticancer drugs. The diselenide bond, as a redox-sensitive linkage, was designed in such a manner that it is located at the hydrophilic-hydrophobic hinge to allow complete collapse of the micelle and thus efficient drug release in redox environments. The amphiphilic block copolymers self-assembled into micelles at concentrations higher than the critical micelle concentration (CMC) in an aqueous environment. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses showed that the micelles were spherical with an average diameter of 120 nm. The insoluble anticancer drug paclitaxel (PTX) was loaded into micelles, and its triggered release behavior under different redox conditions was verified. Folate-targeting micelles showed an enhanced uptake in 4T1 breast cancer cells and in vitro cytotoxicity by flow cytometry and (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay, respectively. Delayed tumor growth was confirmed in the subcutaneously implanted 4T1 breast cancer in mice after intraperitoneal injection. The proposed redox-responsive copolymer offers a new type of biomaterial for drug delivery into cancer cells in vivo. STATEMENT OF SIGNIFICANCE: On-demand drug actuation is highly desired. Redox-responsive polymeric DDSs have been shown to be able to respond and release their cargo in a selective manner when encountering a significant change in the potential difference, such as that present between cancerous and healthy tissues. This study offers an added advantage to the field of redox-responsive polymers by reporting a new type of shell-sheddable micelle based on an amphiphilic triblock co-polymer, containing diselenide as a redox-sensitive linkage. The linkage was smartly located at the hydrophilic-hydrophilic bridge in the co-polymer offering complete collapse of the micelle when exposed to the right trigger. The system was able to delay tumor growth and reduce toxicity in a breast cancer tumor model following intraperitoneal injection in mice.

Smart liposomal drug delivery for treatment of oxidative stress model in human embryonic stem cell-derived retinal pigment epithelial cells.

Oxidative stress has been implicated in the progression of age-related macular degeneration (AMD). Treatment with antioxidants seems to delay progression of AMD. In this study, we suggested an antioxidant delivery system based on redox-sensitive liposome composed of phospholipids and a diselenide centered alkyl chain. Dynamic light scattering assessment indicated that the liposomes had an average size of 140 nm with a polydispersity index below 0.2. The percentage of encapsulation efficiency of the liposomes was calculated by high-performance liquid chromatography. The carriers were loaded with N-acetyl cysteine as a model antioxidant drug. We demonstrated responsiveness of the nanocarrier and its efficiency in drug delivery in an oxidative stress model of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells. The modeled cells treated with diselenide containing liposomes loaded with 10 mM NAC, showed a better therapeutic effect with a cell metabolic activity of 90%, which was significantly higher compared to insensitive liposomes or NAC treated groups (P < 0.05). In addition, the expression of oxidative-sensitive gene markers in diselenide containing liposomes groups were improved. Our results demonstrated fabricated smart liposomes opens new opportunity for targeted treatment of retinal degeneration.

Breast tissue decomposition with spectral distortion correction: a postmortem study.

PURPOSE: To investigate the feasibility of an accurate measurement of water, lipid, and protein composition of breast tissue using a photon-counting spectral computed tomography (CT) with spectral distortion corrections. METHODS: Thirty-eight postmortem breasts were imaged with a cadmium-zinc-telluride-based photon-counting spectral CT system at 100 kV. The energy-resolving capability of the photon-counting detector was used to separate photons into low and high energy bins with a splitting energy of 42 keV. The estimated mean glandular dose for each breast ranged from 1.8 to 2.2 mGy. Two spectral distortion correction techniques were implemented, respectively, on the raw images to correct the nonlinear detector response due to pulse pileup and charge-sharing artifacts. Dual energy decomposition was then used to characterize each breast in terms of water, lipid, and protein content. In the meantime, the breasts were chemically decomposed into their respective water, lipid, and protein components to provide a gold standard for comparison with dual energy decomposition results. RESULTS: The accuracy of the tissue compositional measurement with spectral CT was determined by comparing to the reference standard from chemical analysis. The averaged root-mean-square error in percentage composition was reduced from 15.5% to 2.8% after spectral distortion corrections. CONCLUSIONS: The results indicate that spectral CT can be used to quantify the water, lipid, and protein content in breast tissue. The accuracy of the compositional analysis depends on the applied spectral distortion correction technique.