Smart albumin-loaded Rose Bengal and doxorubicin nanoparticles for breast cancer therapy.

Objective: To synthesise HSA-RB-DOX nanoparticles, measure its characteristics and preliminarily evaluate its anti-cancer effects.Methods: Doxorubicin (DOX) and Rose Bengal (RB) were co-delivered using albumin as a carrier. HSA-RB-DOX nanoparticles were prepared by RB-induced self-assembly of albumin. Its characteristics were measured and anti-cancer effects were tested in MCF-7 cells and tumour-bearing mice.Results: HSA-RB-DOX nanoparticle with a mean size of 42 nm was stable in different medium and behaved controlled release characteristic. It was well took in MCF-7 cells and inhibited MCF-7 cells proliferation by inducing reactive oxygen species (ROS) production. It retained a much higher blood concentration up to 12 h and accumulated more in tumour tissues. In tumour-bearing mice, HSA-RB-DOX nanoparticles inhibited tumour growth and even decreased its volume from 100 to 50 mm3, with barely no influence on body weight.Conclusions: HSA-RB-DOX nanoparticles may be potentially used for enhanced treatment of breast cancer.

Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells.

Retigeric acid B (RAB), a natural compound isolated from lichen, has been demonstrated to inhibit cell growth and promote apoptosis in prostate cancer (PCa) cells. The present study evaluated the function of RAB combined with clinical chemotherapeutic drugs in PCa cell lines by MTT assay, reverse transcription quantitative polymerase chain reaction and western blot analysis, and identified that RAB at low doses produced significant synergistic cytotoxicity in combination with cisplatin (CDDP); however, no marked synergism between RAB and the other chemotherapeutics was observed. Additional studies revealed that RAB exerted an inhibitory effect on DNA damage repair pathways, including the nucleotide excision repair and mismatch repair pathways, which are involved in the sensitivity to CDDP-based chemotherapy, as suggested by the significantly downregulated expression of certain associated repair proteins. Notably, Excision repair cross-complementing 1, a critical gene in the nucleotide excision repair pathway, exhibited the most significant decrease. When combined with CDDP, RAB-mediated impairment of DNA repair resulted in prolonged DNA damage, as demonstrated by the long-lasting appearance of phosphorylation of histone H2AX at Ser139, which potentially enhanced the chemosensitivity to CDDP. Concurrently, the proapoptotic protein death receptor 5 (DR5) was activated by RAB, which also enhanced the chemotherapeutic response of CDDP. Knockdown of DR5 partially blocked RAB-CDDP synergism, suggesting the crucial involvement of DR5 in this event. The results of the present study identified that RAB functioned synergistically with CDDP to increase the efficacy of CDDP by inhibiting DNA damage repair and activating DR5, suggesting the mechanistic basis for the antitumor effect of RAB in combination with current chemotherapeutics.

Strategies to release doxorubicin from doxorubicin delivery vehicles.

Doxorubicin (DOX) is one of the most effective cytotoxic anticancer drugs and has been successfully applied in clinics to treat haematological malignancies and a broad range of solid tumours. However, the clinical applications of DOX have long been limited due to severe dose-dependent toxicities. Recent advances in the development of DOX delivery vehicles have addressed some of the non-specific toxicity challenges associated with DOX. These DOX-loaded vehicles are designed to release DOX in cancer cells effectively by cutting off linkers between DOX and carriers response to stimuli. This article focuses on various strategies that serve as potential tools to release DOX from DOX-loaded vehicles efficiently to achieve a higher DOX concentration in tumour tissue and a lower concentration in normal tissue. With a deeper understanding of the differences between normal and tumour tissues, it might be possible to design ever more promising prodrug systems for DOX delivery and cancer therapy in the near future.

Prodrug-based nano-drug delivery system for co-encapsulate paclitaxel and carboplatin for lung cancer treatment.

CONTEXT: Paclitaxel (PTX) and carboplatin (CBP) are widely used for the combined chemotherapy of non-small cell lung cancer (NSCLC). However, the development of multidrug resistance of cancer cells, as well as systemic toxic side effects resulting from nonspecific localization of anticancer drugs to non-tumor areas are major obstacles to the success of chemotherapy in treating cancers. OBJECTIVE: This study aimed to engineer a prodrug-based nano-drug delivery system for co-encapsulate hydrophilic (CBP) and hydrophobic anti-tumor drugs (PTX). This system was expected to resolve the multidrug resistance cause by single drug, and the dual-drug-loaded liposome was also planned to specifically target the cancer cells without obvious influence on normal cells and tissues. METHODS: In this paper, PLGA-PEG-CBP was synthesized by the conjugation between the carboxylic group of PLGA-PEG-COOH and the amino group of CBP. Then, self-assembled nanoparticles for combination delivery of PTX and PLGA-PEG-CBP (PTX/CBP NPs) were prepared by solvent displacement technique. The in vitro and in vivo anti-tumor efficacy was assessed in NCL-H460 human non-small cell lung carcinoma cell line. RESULTS: PTX/CBP NPs achieved the highest cytotoxic effect among all formulations in vitro, as compared with single drug delivery NPs. In vivo investigation on NSCLC animal models showed that co-delivery of PTX and CBP possessed high tumor-targeting capacity and strong anti-tumor activity. CONCLUSIONS: The PTX/CBP NPs constructed in this research offers an effective strategy for targeted combinational lung cancer therapy.

[Effect of fumigation therapy with yinxieling on T-bet and GATA-3 protein expression in the peripheral blood monocyte of patients with psoriasis vulgaris].

OBJECTIVE: To evaluate the effect of fumigating with Yinxieling (YXL) in treating patients with psoriasis vulgaris and its influence on T-bet and GATA-3 protein expressions in peripheral blood monocyte (PBMC). METHODS: Western blot method was employed to detect the T-bet and GATA-3 protein expressions in PBMC of 30 psoriasis vulgaris patients before and after they received fumigation therapy with YXL, also in 25 healthy persons for controls. The therapeutic efficacy was observed and the relationship between PASI scores and levels of T-bet and GATA-3 analyzed. RESULTS: After treatment, 12 out of the 30 patients were cured, 9 were markedly effective, 8 effective and 1 unchanged, the cure rate being 40.0% and the effective rate 96.7%. Level of T-bet expression in PBMC of patients was 1.7917 +/- 0.3840, which was higher than that of healthy persons (0.8860 +/- 0.1486, P < 0.01), but the GATA3 expression was lower than that in control (0.8777 +/- 0.3114 vs. 1.2384 +/- 0.1783, P < 0.01). However, the two indexes were restored after fumigation to 1.3410 +/- 0.3642 and 1.0883 +/- 0.2435 respectively, showing significant difference to those before fumigation (P < 0.01). Correlation analysis showed that PASI score was positively correlated with level of T-bet expression (r = 0.7448, P < 0.01) and negatively correlated with level of GATA-3 expression (r = -0.8291, P < 0.01). CONCLUSION: Fumigation therapy is effective in treating psoriasis vulgaris, its mechanism is possibly by way of modulating the equilibrium of the transcription factors T-bet and GATA-3 protein expressions in PBMC, and rectifying the immune abnormality of Th1/Th2 subsets imbalance.