Targeted Biomimetic Nanoparticles for Synergistic Combination Chemotherapy of Paclitaxel and Doxorubicin

Codelivery of multiple chemotherapeutics has become a versatile strategy in recent cancer treatment, but the antagonistic behavior of combined drugs limited their application. We developed a recombinant high-density lipoprotein (rHDL) nanoparticle for the precise coencapsulation and codelivery of two established drugs and hypothesized that they could act synergistically to improve anticancer efficacy. The coloaded rHDL was formulated by passively incorporating hydrophobic paclitaxel (PTX), and subsequently remotely loading hydrophilic doxorubicin (Dox) into the same nanoparticles. The resultant rHDL system restored targeted delivery function toward cancer cells via scavenger receptor class B (SR-BI), as confirmed by <i>in vitro</i> confocal imaging and flow cytometry. These coloaded rHDL nanoparticles were remarkably effective in increasing the ratiometric accumulation of drugs in cancer cells and enhancing antitumor response at synergistic drug ratios. In particular, they exhibited more efficacious anticancer effects in an <i>in vitro</i> cytotoxicity evaluation and in a xenograft tumor model of hepatoma compared with free drug cocktail solutions. These results confirm that the coloaded rHDL nanoparticles are promising candidates for the synergistic delivery of drugs with diverse physicochemical properties in cancer treatment integrating efficiency and safety considerations

Redox-responsive PEGylated self-assembled prodrug-nanoparticles formed by single disulfide bond bridge periplocymarin-vitamin E conjugate for liver cancer chemotherapy

<p>Periplocymarin (PPM), a cardiac glycoside, has a narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity which hinder its wide clinical applications in cancer treatment. Herein, we report novel redox-responsive prodrug-nanoparticles (MPSSV-NPs) self-assembled by co-nanoprecipitation of PPM-vitamin E conjugate and a PEG derivative of linoleate (mPEG2000-LA) in water. It was found that the characteristics of PPM-vitamin E nanoparticles (PSSV-NPs) were improved through co-nanoprecipitation with increased percentages of mPEG2000-LA. Moreover, the MPSSV-NPs were optimized according to the <i>in vitro</i> release and cytotoxicity study. Furthermore, the optimized MPSSV-NPs dramatically enhanced the circulation time and tumor distribution of PSSV-NPs after single intravenous injection. The <i>in vivo</i> studies in malignant H₂₂-bearing mice revealed that MPSSV-NPs could effectively suppress tumor growth without causing obvious systemic toxicity. Altogether, these results suggested that MPSSV-NPs could offer a safe, multifunctional and viable nanoplatform for cardiac glycosides in cancer treatment.</p

Results of the docking of 5a (green), 5b (blue), 5c (yellow), 5d (magenta), 5e (cyan), 5f (orange), and native ligand tiamulin (red) into the PTC model binding site.

<p>The 50S subunit of <i>Deinococcus radiodurans</i> cut in half to reveal the binding site.</p

Comparison of eating quality and physicochemical properties between Japanese and Chinese rice cultivars

<p>In this study, we evaluated 16 Japanese and Chinese rice cultivars in terms of their main chemical components, iodine absorption curve, apparent amylose content (AAC), pasting property, resistant starch content, physical properties, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, and enzyme activity. Based on these quality evaluations, we concluded that Chinese rice varieties are characterized by a high protein and the grain texture after cooking has high hardness and low stickiness. In a previous study, we developed a novel formula for estimating AAC based on the iodine absorption curve. The validation test showed a determination coefficient of 0.996 for estimating AAC of Chinese rice cultivars as unknown samples. In the present study, we developed a novel formulae for estimating the balance degree of the surface layer of cooked rice (A3/A1: a ratio of workload of stickiness and hardness) based on the iodine absorption curve obtained using milled rice.</p

Structural formulas of pleuromutilin (1) and derivatives.

<p>Structural formulas of pleuromutilin (1) and derivatives.</p

Zone of Inhibition of 5a–f for MRSA, MRSE, E. coli and S.agalactia (in mm).

<p>Zone of Inhibition of 5a–f for MRSA, MRSE, E. coli and S.agalactia (in mm).</p

Crystal structure of compound 4.

<p>(a) ORTEP diagram for compound <b>4</b> with ellipsoids set at 50% probability (hydrogen atoms were omitted for clarity). (b) A perspective view of the molecular packing of <b>4</b> viewed along the α axis.</p

Scheme for the synthesis of target compounds 5a–f.

<p>Scheme for the synthesis of target compounds 5a–f.</p

MIC (μg/mL)of 5a–f for MRSA, MRSE, E. coli and S.agalactia.

<p>MIC (μg/mL)of 5a–f for MRSA, MRSE, E. coli and S.agalactia.</p

MOESM1 of Direct reprogramming of mouse fibroblasts into neural cells via Porphyra yezoensis polysaccharide based high efficient gene co-delivery

Additional file 1: Figure S1. Fourier-Transform infrared spectra of Porphyra yezoensis polysaccharide (PYP) and ethylenediamine modified Porphyra yezoensis polysaccharide (Ed-PYP). Figure S2. Electrophoretic mobility of plasmid in Ed-PYP-plasmid Ascl1, Brn4 and Tcf3 (pABT) nanoparticles at various weight ratios. Lane 1–3, free plasmids Ascl1, Brn4 and Tcf3 from left to right; Lane 4–9, Ed-PYP: pABT weight ratios of 10:1, 20:1, 40:1, 80:1, 150:1, and 300:1, respectively. Figure S3. Cytotoxicity assay. Bar 1, 3T6 cells treated with Ed-PYP; bar2, free plasmid group Ascl1, Brn4 and Tcf3 (pABT) (control group); bars 3–8, ethylenediamine modified Porphyra yezoensis polysaccharide (Ed-PYP)–pABT nanoparticles at ratios of 20:1, 40:1, 80:1, 150:1, 300:1, and 400:1 from left to right, respectively; bar 9, PEI–pABT; bars 10, Lipofectamine 2000(Lip2000)-pABT. Figure S4. Characterization of ethylenediamine modified Porphyra yezoensis polysaccharide (Ed-PYP)-pABT nanoparticles. (A) Zeta-potential results. Notes: Bar 1, naked plasmid group Ascl1, Brn4 and Tcf3 (pABT); bar 2, Porphyra yezoensis polysaccharide (PYP); bar 3, ethylenediamine modified Porphyra yezoensis polysaccharide (Ed-PYP); bars 4–6, Ed-PYP–pABT nanoparticles prepared at various Ed-PYP: pABT weight ratios-20:1, 40:1, and 80:1 from left to right, respectively (means±standard deviation of measurements from three replicates). (B) Size distribution of the nanoparticles at Ed-PYP: pABT weight ratios of 20:1, 40:1, and 80:1, respectively. (C) Transmission electron microscopy image of the nanoparticles at an Ed-PYP: pABT weight ratio of 40:1. (D) Particle-size distribution of the nanoparticles at an Ed-PYP: pABT weight ratio of 40:1