Jug-PLGA-NPs, a New Form of Juglone with Enhanced Efficiency and Reduced Toxicity on Melanoma.

OBJECTIVE: To verrify the anti-tumor efficacy and toxicity between juglone (Jug) and Jug-loaded PLGA nanoparticles (Jug-PLGA-NPs). METHODS: Jug-PLGA-NPs were prepared by ultrasonic emulsification. The anti-tumor activity of Jug (2, 3, 4 µg/mL) and Jug-PLGA-NPs (Jug: 2, 3, 4 µg/mL) in vitro was measured by MTT assay and cell apoptosis analysis. The distribution, anti-tumor effect and biological safety in vivo was evaluated on A375 nude mice. RESULTS: With the advantage of good penetration and targeting properties, Jug-PLGA-NPs significantly inhibited proliferation and migration of melanoma cells both in vitro and in vivo (P<0.05 or P<0.01) with acceptable biocompatibility. CONCLUSIONS: Jug can inhibit the growth of melanoma but is highly toxic. With the advantage of sustained release, tumor targeting, anti-tumor activity and acceptable biological safety, Jug-PLGA-NPs provide a new pharmaceutical form for future application of Jug.

[Evaluation for preparation and anticancer efficacy in vitro of drug-loaded nanoerythrosomes].

The objective of this study is to develop a new-type biodegradable, biocompatible curcumin-loaded nanoerythrosomes (Cur-RBC-NPs) by means of the sonication method. The size of Cur-RBC-NPs was optimized by varying drug loading parameters. The morphology, size distribution, stability, in vitro release pattern, cellular uptake of nanoparticles and in vitro anti-tumor effects were evaluated, respectively. The results showed the prepared Cur-RBC-NPs were nearly uniform spheres, with an average diameter of (245.7 ± 1.3) nm. Encapsulation efficiency (EE) and load efficiency (LE) of Cur-RBC-NPs were 50.65% ± 1.36% and 6.27% ± 0.29%. And the nanoparticles had a good sustained release property. According to the in vitro experiment, Cur-RBC-NPs were effectively taken in by tumor cells, and exhibited a significant anti-tumor effect. In conclusion, the method for preparing Cur-RBC-NPs is convenient, with a good sustained release behavior and anti-tumor efficacy, and so expected to be a new-type nano-drug delivery system in clinical practice.

Targeted delivery of miR-200c/DOC to inhibit cancer stem cells and cancer cells by the gelatinases-stimuli nanoparticles.

Cancer stem cells (CSCs) are recently discovered as vital obstacles for the successful cancer therapy. Emerging evidences suggest that miR-200c functions as an effective CSCs inhibitor and can restore sensitivity to microtubule-targeting drugs. In the present work, the intelligent gelatinases-stimuli nanoparticles (NPs) was set up to co-deliver miR-200c and docetaxel (DOC) to verify their synergetic effects on inhibition of CSCs and non-CSC cancer cells. After tumor cells were treated with miR-200c NPs, miR-200c and its targeted gene class III beta-tubulin (TUBB3)TUBB3 expression were evaluated. The effects of miR-200c/DOC NPs on tumor cell viability, migration and invasion as well as the expression of E-cadherin and CD44 were studied. The antitumor effects of miR-200c/DOC NPs were compared with DOC NPs in xenograft gastric cancer mice. Moreover, the residual tumors after treatment were subcutaneously seeded into nude mice to further investigate the effective maintenance of NPs. We found that the gelatinases-stimuli NPs facilitated miR-200c into cells, achieving sustained miR-200c expression in tumor cells during 9 days. The miR-200c/DOC NPs significantly enhanced cytotoxicity of DOC, possibly by decreasing TUBB3 level, and reversing EMT. The miR-200c NPs achieved high levels of in vivo accumulation and long retention in gastric cancer xenografts after intravenous administration. The miR-200c/DOC NPs prominently suppressed in vivo tumor growth with elevated miR-200c and E-cadherin levels and down-regulated TUBB3 and CD44 expressions. When the residual tumors after miR-200c/DOC NPs treatment were re-transplanted into nude mice, the tumors demonstrated the slowest growth speed. The miR-200c/DOC NPs may provide a promising modality for co-delivery of nucleic acid and drugs to simultaneously inhibit CSCs and non-CSC cancer cells.

Gelatinase-stimuli strategy enhances the tumor delivery and therapeutic efficacy of docetaxel-loaded poly(ethylene glycol)-poly(ɛ-caprolactone) nanoparticles.

Nanoscale drug carriers have been extensively developed to improve drug therapeutic efficiency. However, delivery of chemotherapeutic agents to tumor tissues and cells has not been favorably managed. In this study, we developed a novel "intelligent" nanoparticle, consisting of a gelatinase-cleavage peptide with poly(ethylene glycol) (PEG) and poly(ɛ-caprolactone) (PCL)-based structure for tumor-targeted docetaxel delivery (DOC-TNPs). The docetaxel-loaded PEG-PCL nanoparticles (DOC-NPs) that did not display gelatinase-stimuli behaviors were used as a control. We found clear evidence that the DOC-TNPs were transformed by gelatinases, allowing drug release and enhancing the cellular uptake of DOC (P < 0.01). In vivo biodistribution study demonstrated that targeted DOC-TNPs could accumulate and remain in the tumor regions, whereas non-targeted DOC-NPs rapidly eliminated from the tumor tissues. DOC-TNPs exhibited higher tumor growth suppression than commercialized Taxotere(®) (docetaxel; Jiangsu Hengrui Medicine Company, Jiangsu, China) and DOC-NPs on hepatic H22 tumor model via intravenous administration (P < 0.01). Both in vitro and in vivo experiments suggest that the gelatinase-mediated nanoscale delivery system is promising for improvement of antitumor efficacy in various overexpressed gelatinase cancers.