Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths worldwide largely due to lack of effective targeted drugs to simultaneously block multiple cancer-driving pathways. The identification of all-trans retinoic acid (ATRA) as a potent Pin1 inhibitor provides a promising candidate for HCC targeted therapy because Pin1 is overexpressed in most HCC and activates numerous cancer-driving pathways. However, the efficacy of ATRA against solid tumors is limited due to its short half-life of 45min in humans. A slow-releasing ATRA formulation inhibits solid tumors such as HCC, but can be used only in animals. Here, we developed a one-step, cost-effective route to produce a novel biocompatible, biodegradable, and non-toxic controlled release formulation of ATRA for effective HCC therapy. We used supercritical carbon dioxide process to encapsulate ATRA in largely uniform poly L-lactic acid (PLLA) microparticles, with the efficiency of 91.4% and yield of 68.3%, and ~4-fold higher C and AUC over the slow-releasing ATRA formulation. ATRA-PLLA microparticles had good biocompatibility, and significantly enhanced the inhibitory potency of ATRA on HCC cell growth, improving IC by over 3-fold. ATRA-PLLA microparticles exerted its efficacy likely through degrading Pin1 and inhibiting multiple Pin1-regulated cancer pathways and cell cycle progression. Indeed, Pin1 knock-down abolished ATRA inhibitory effects on HCC cells and ATRA-PLLA did not inhibit normal liver cells, as expected because ATRA selectively inhibits active Pin1 in cancer cells. Moreover ATRA-PLLA microparticles significantly enhanced the efficacy of ATRA against HCC tumor growth in mice through reducing Pin1, with a better potency than the slow-releasing ATRA formulation, consistent with its improved pharmacokinetic profiles. This study illustrates an effective platform to produce controlled release formulation of anti-cancer drugs, and ATRA-PLLA microparticles might be a promising targeted drug for HCC therapy as PLLA is biocompatible, biodegradable and nontoxic to humans.

No abstract

To solve the problem of synthesized magnetic nanoparticles in cancer therapy, a new drug delivery system synthesized from bacteria was used to load cytosine arabinoside (Ara-C). Genipin (GP) and poly- l -glutamic acid (PLGA) were selected as dual cross-linkers. The preparation and characterization of Ara-C-loaded GP-PLGA-modified bacterial magnetosomes (BMs) (ABMs-P), as well as their in vitro antitumor effects, were all investigated. Transmission electron micrographs (TEM) and Fourier transform infrared (FTIR) spectroscopy suggested that Ara-C could be bound to the membrane of BMs modified by GP-PLGA. The diameters of the BMs and ABMs-P were 42.0±8.6 nm and 74.9±8.2 nm, respectively. The zeta potential revealed that the nanoparticles were stable. Moreover, this system exhibited optimal drug-loading properties and long-term release behavior. The optimal encapsulation efficiency and drug-loading were 64.1%±6.6% and 38.9%±2.4%, respectively, and ABMs-P could effectively release 90% Ara-C within 40 days, without the release of an initial burst. In addition, in vitro antitumor experiments elucidated that ABMs-P is cytotoxic to HL-60 cell lines, with an inhibition rate of 95%. The method of coupling drugs on BMs using dual cross-linkers is effective, and our results reveal that this new system has potential applications for drug delivery in the future.

No abstract

No abstract

Abstract:To ease the side effects triggered by cytosine arabinoside (Ara-C) for acute leukemia treatment, a novel magnetic targeting anti-tumor drug delivery system was constructed through bacterial magnetosomes (BMs) from Magnetospirillum magneticum AMB-1 combined with Ara-C by crosslinking of genipin (GP). The results showed that Ara-C could be bonded onto the membrane surface of BMs effectively through chemical crosslinking induced by dual hand reagents GP. The average diameters of BMs and Ara-C-coupled BMs (ABMs) were 42.0 ± 8.6 and 72.7 ± 6.0 nm respectively, and the zeta potentials (−38.1 ± 9.1) revealed that these systems were stable, confirming the stability of the system. The optimal encapsulation efficiency and drug loading were 89.05% ± 2.33% and 47.05% ± 0.64% respectively when crosslinking reaction lasted for 72 h. The system also presented long-term stability and release behaviors without initial burst release (Ara-C could be released 80% within three months). Our results indicate that BMs have great potential in biomedical and clinical fields as a novel anti-tumor drug carrier.

No abstract

BackgroundThe release of antibiotics into aquatic environments has made the treatment of wastewater containing antibiotics a world-wide public health problem. The ability of microbial fuel cells (MFCs) to harvest electricity from organic waste and renewable biomass is attracting increased interest in wastewater treatment. In this paper we investigated the bioelectrochemical response of an electroactive mixed-culture biofilm in MFC to different tobramycin concentrations.ResultsThe electroactive biofilms showed a high degree of robustness against tobramycin at the level of μg/L. The current generation responses of the biofilms were affected by the presence of tobramycin. The inhibition ratio of the MFC increased exponentially with the tobramycin concentrations in the range of 0.1-1.9 g/L. The bacterial communities of the biofilms vary with the concentrations of tobramycin, the equilibrium of which is critical for the stability of electroactive biofilms based-MFC.ConclusionsExperimental results demonstrate that the electroactive biofilm-based MFC is robust against antibiotics at the level of μg/L, but sensitive to changes in antibiotic concentration at the level of g/L. These results could provide significant information about the effects of antibiotics on the performance MFC as a waste-treatment technology.