Mitochondria-anchoring self-assembled nanoparticles for multi-path energy depletion: A "nano bomb" in chemo-co-starvation therapy.

As the main systemic treatment for triple-negative breast cancer (TNBC), the bleak medical prognosis of chemotherapy resulted in impaired life quality by tumor recurrence and metastasis. The feasible cancer starvation therapy could inhibit tumor progression by blocking energy supplements, however, the mono-therapeutic modality showed limited curing efficacy due to heterogeneity and abnormal energy metabolism of TNBC. Thus, the development of a synergistic nano-therapeutic modality involving different anti-tumor mechanisms to simultaneously transport medicines to the organelle where metabolism took place, might remarkably improve curing efficacy, targeting ability, and bio-safety. Herein, the hybrid BLG@TPGS NPs were prepared by doping multi-path energy inhibitors Berberine (BBR) and Lonidamine (LND) as well as the chemotherapeutic agent Gambogic acid (GA). Our research indicated that Nanobomb-BLG@TPGS NPs inherited the mitochondria targeting ability from BBR to accumulate precisely at the "energy factory" mitochondria, and then induce starvation therapy to efficiently eradicated cancer cells by coordinately powered off tumor cells via a "three-prone strategy" to cut off mitochondrial respiration, glycolysis, and glutamine metabolism. The inhibition of tumor proliferation and migration was enlarged by the synergistic combination with chemotherapy. Besides, apoptosis via mitochondria pathway and mitochondria fragmentation supported the hypothesis that NPs eliminated MDA-MB-231 cells by violently attacking MDA-MB-231 cells and especially the mitochondria. In summary, this synergistic chemo-co-starvation nanomedicine proposed an innovative site-specific targeting strategy for improved tumor treatment and decreased toxicity to normal tissues, which provided an option for clinical TNBC-sensitive treatment.

Enhanced Anti-Rheumatoid Arthritis Activity of Total Alkaloids from Picrasma Quassioides in Collagen-Induced Arthritis Rats by a Targeted Drug Delivery System.

New drug delivery systems have rarely been used in the formulation of traditional Chinese medicine, especially those that are crude active Chinese medicinal ingredients. In the present study, hyaluronic acid decorated lipid-polymer hybrid nanoparticles were used to prepare a targeted drug delivery system (TDDS) for total alkaloid extract from Picrasma quassioides (TAPQ) to improve its targeting property and anti-inflammatory activity. Picrasma quassioides, a common-used traditional Chinese medicine (TCM), containing a series of hydrophobic total alkaloids including ß-carboline and canthin-6-one alkaloids show great anti-inflammatory activity. However, its high toxicity (IC50= 8.088±0.903 µg/ml), poor water solubility (need to dissolve with 0.8% Tween-80) and poor targeting property severely limits its clinical application. Herein, hyaluronic acid (HA) decorated lipid-polymer hybrid nanoparticles loaded with TAPQ (TAPQ-NPs) were designed to overcome above mentioned deficiencies. TAPQ-NPs have good water solubility, strong anti-inflammatory activity and great joint targeting property. The in vitro anti-inflammatory activity assay showed that the efficacy of TAPQ-NPs was significantly higher than TAPQ(P<0.001). Animal experiments showed that the nanoparticles had good joint targeting property and had strong inhibitory activity against collagen-induced arthritis (CIA). These results indicate that the application of this novel targeted drug delivery system in the formulation of traditional Chinese medicine is feasible.

Chemical constituents and quality control of two Dracocephalum species based on high-performance liquid chromatographic fingerprints coupled with tandem mass spectrometry and chemometrics.

Two similar Dracocephalum species, namely, Dracocephalum tanguticum Maxim and Dracocephalum moldavica L, are commonly used as ethnic medicines in China. Here we describe a strategy of combining high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry, as well as fingerprints and chemometrics for characterization and discrimination of chemical constituents on the two herbs. A total of 49 compounds including 33 flavonoids, 5 phenylethanol glycosides, 1 coumarin glycoside, 8 organic acids, and 2 other types of compounds were unambiguously or tentatively identified from the two Dracocephalum species. Among the compounds identified, 26 were characterized for the first time and 4 compounds, rosmarinic acid (7), salvianolic acid B (10), luteoloside (22), diosmetin-7-O-glucoside (28), were inferred as common constituents for the two herbs. Flavonoids featured in these two Dracocephalum species while their types presented significant differences. Acacetin (45) and acacetin glycosides (acatetin-7-O-glucuronide (30), acacetin-7-O-(6"-O-malonyl) glucoside (33), buddleoside (34), tilianin (35), and agastachoside (42)) were detected only in D. moldavica, which can be used to discriminate two herbal medicines. In addition, six characteristic constitutes in D. tanguticum were simultaneously quantified. Moreover, the induced chemometrics methods including similarity analysis and hierarchical clustering analysis were successfully applied for origin discrimination and quality evaluation of D. tanguticum and D. moldavica.

Four new quassinoids from the roots of Eurycoma longifolia Jack.

Seven compounds were isolated from the roots of Eurycoma longifolia, and characterized by comprehensive analysis of 1D and 2D NMR experiments along with single crystal X-ray diffraction. Among them, four new quassinoids were identified and three of them were diastereomers for each other. Compounds 1-7 were evaluated for cytotoxicities against HT-29, MCF-7, LOVO, BGC-823, MGC-803, HepG2, HeLa, and A549 cancer cell lines. Compounds 2 and 5 exhibited the lowest IC50 values of 24.9 µM, 11.8 µM, and 44.1 µM, 14.1 µM towards MCF-7, MGC-803 cancer cell lines, respectively, while compound 6 exhibited moderate cytotoxicity towards all the selected cancer cell lines.

Adeno-associated virus-mediated local delivery of LIGHT suppresses tumorigenesis in a murine cervical cancer model.

LIGHT is a tumor necrosis factor superfamily ligand that is considered as a promising candidate for cancer therapy. It has a potent antitumor activity through establishing lymphoid-like tissues inside tumor sites and recruiting naive T cells into the tumor. In this study, we examined the possibility of antitumor activity by expressing LIGHT in cervical cancer (CC) model. A recombinant adeno-associated virus (AAV) vector was chosen for the transfer, based on its transfection efficiency and lack of detectable pathology. In vitro transfer of recombinant AAV vector expressing LIGHT (AAV-LIGHT) stimulated T-lymphocyte proliferation and activation. AAV-mediated gene transfer of LIGHT by intratumoral injection exerted a very potent antitumor effect against preexisting TC-1 cell CC in C57BL/6 mice. This study confirmed that AAV-LIGHT regressed tumor growth by activating cytotoxic T lymphocyte, enhancing infiltration of inflammatory cells in tumor and increasing stimulatory cytokine expression in tumor microenvironment. Therefore, AAV-LIGHT therapy might have potential utility for the treatment of CC.

Janceolaroside A and janceoside A, two new compounds from the stems and roots of Jasminum lanceolarium.

From the stems and roots of Jasminum lanceolarium Roxb., two new compounds, janceolaroside A and janceoside A, have been isolated along with three known compounds, (-)olivil 4'-O-beta-D-glucopyranoside, (+)-cycloolivil-6-O-beta-D-glucopyranoside and syringin. The structures of the new compounds were determined by spectroscopic methods.