Biotherapeutic Nanoparticles of Poly(Ferulic Acid) Delivering Doxorubicin for Cancer Therapy.

Chemotherapy drugs have been known as the mainstay of cancer treatment; however, they have inevitable side effects when used in isolation. Drug-loaded nanosystems represent a breakthrough drug delivery platform that enhances the treatment index of chemotherapy in cancer treatment; further, it compensates for the deficiency of body toxicity and significantly enhances antitumor effects. Given that designing biosafe nanodrugs requires nontoxicity of carriers, novel polymers, synthesized from natural products, with good biocompatibility and biodegradation are the preferred drug carriers. Ferulic acid (FA) derived from plants can be chemically modified to form poly(ferulic acid) (PFA) with reassuring biosafety. PFA-loading doxorubicin (DOX) was properly self-assembled into stable PFA@DOX nanoparticles (NPs), which released payloads continuously under slightly acidic conditions in vitro, ensuring effective drug delivery in acidic tumor microenvironments. In vivo antitumor therapy showed that the PFA nanocarriers could promote accumulation and retention at the tumor site for superior tumor suppression, while the PFA@DOX NPs reduced the physical toxicity of free DOX, thereby, improving safety. Therefore, such drug-loaded NPs can exert considerable influence over an antitumor action for potential clinical translation in the future.

H2O2-responsive nano-prodrug for podophyllotoxin delivery.

The tumor microenvironment is different from that of normal tissue; therefore, the development of a prodrug that retains its efficacy in the tumor microenvironment can be useful in enhancing the anticancer properties of podophyllotoxin. An innovative podophyllotoxin prodrug (POD-PEG) was designed by linking podophyllotoxin to poly(ethylene glycol)(n) monomethacrylate with a H2O2-responsive oxalate ester bond. POD-PEG can self-assemble into stable nanoparticles (POD-PEG NPs). In vitro experiments demonstrated that the POD-PEG NPs can be activated by hydrogen peroxide resulting in podophyllotoxin release and are highly toxic against colon carcinoma CT26 cells. In vivo biodistribution studies demonstrate that PEGylated POD-PEG NPs are capable of prolonging blood circulation. Intravenous injection of POD-PEG NPs into CT26 tumor-bearing Balb/c mice resulted in a significantly enhanced therapeutic efficacy against tumors, with no significant systemic toxicity. Therefore, this H2O2-responsive prodrug delivery system exhibits good biosafety and provides a novel strategy for the development of drug delivery systems.

Integration of laminar flow extraction and capillary electrophoretic separation in one microfluidic chip for detection of plant alkaloids in blood samples.

The design, construction and testing for integration of liquid-liquid extraction (EX) and capillary electrophoretic (CE) separation on one glass microchip was reported. In this EX-CE chip, a 1.5 cm-long and 200 µm-wide EX channel was used for extraction based on the two-phase laminar flow, followed by a single-cross CE unit for on-line analysis without any auxiliary devices. One side of the EX channel surface for the organic solvent phase was selectively modified to be hydrophobic while the surface of the other side for the aqueous phase remained hydrophilic, and the extraction product reservoir is also used as the sample reservoir for the subsequent chip separation in the CE channel. With the surface-directed liquid flow behavior and liquid level adjustment in various reservoirs of the EX-CE chip, no disturbance occurred between the extraction (EX) and capillary electrophoretic (CE) units. A small heating block was placed under the chip to accelerate solvent evaporation after liquid-liquid extraction. Sanguinarine (SAN), a plant alkaloid, was used as a model analyte to evaluate the performance of the EX-CE chip. The influences of organic solvent type and liquid flow speed on the extraction efficiency were investigated. Rhodamine 123 (Rh123) was used as an internal standard for quantification of Sanguinarine (SAN) in a physiological buffer (e.g. PBS) or blood samples. A good linearity in the concentration range of 0.05 µg mL-1 to 0.1 mg mL-1 for SAN in PBS was obtained, with the detection limit of 0.5 ng mL-1. Good repeatibilities for migration times (RSD of SAN is 0.63%, Rh123 is 0.91%, n = 5) and peak area ratio of SAN to Rh123 (RSD is 1.3%, n = 5) were obtained. For blood sample analysis, only 20 µL of sample was needed, and the whole analysis was finished in 17 min. In addition to the advantages in fast analysis speed, minimum sample handling, potential automation, the reported method showed an on-line sample pre-concentration capability.

A potent tyrosinase activator from Radix Polygoni multiflori and its melanogenesis stimulatory effect in B16 melanoma cells.

Tyrosinase is a key enzyme in melanin biosynthesis. Activators of tyrosinase with stimulatory effects on melanogenesis are beneficial for the treatment of hypopigmentation diseases. In the present study, mushroom tyrosinase activity assay was performed to screen tyrosinase activators from traditional Chinese herbs. Four components from Radix Polygoni multiflori were tested. The most active compound, 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), was found to be a significant tyrosinase activator. The maximal activation was 126% at a concentration of 75.0 microg/mL. The three anthraquinones slightly activated tyrosinase with effects in the range 7-31%. All the compounds were tested in B16 melanoma cells, the anthraquinones were found to inhibit cell proliferation at a concentration of 0.1-2.5 microg/mL, and THSG was found to be non-cytotoxic at a concentration of 0.1-12.5 microg/mL. THSG significantly increased the activity of murine tyrosinase and stimulated melanin biosynthesis in B16 melanoma cells. In conclusion, THSG is a potent tyrosinase activator and stimulator of melanogenesis with potential for the treatment of hypopigmentation disease.

Effects of radix polygoni multiflori components on tyrosinase activity and melanogenesis.

Radix Polygoni multiflori is a herb used effectively to prevent graying and treat skin depigmentation diseases in traditional Chinese medicine but its active ingredients have not been discovered yet. In this investigation, we tested six compounds isolated from Radix Polygoni multiflori, to discover the active component on melanogenesis. Three experiments were performed in the present investigation: mushroom tyrosinase activity, melanin content B16 cell proliferation assay. Among all the six components tested, THSG showed the most potent effects on tyrosinase activation and melanogenesis; it was shown to be a potent tyrosinase activator and a melanogenesis stimulator in this study. On the other hand, we found that gallic acid significantly inhibited tyrosinase and, in addition, anthraquinones were cytotoxic to melanoma cells. They were both harmful to melanogenesis. Therefore, we propose that THSG acts as the active ingredient of Radix Polygoni multiflori on melanogenesis.