In this study, we designed biodegradable polymersomes for co-delivery of an antiangiogenic drug combretastatin-A4 phosphate (CA4P) and doxorubicin (DOX) to collapse tumor neovasculature and inhibit cancer cell proliferation with the aim to achieve synergistic antitumor effects. The polymersomes co-encapsulating DOX and CA4P (Ps-DOX-CA4P) were prepared by solvent evaporation method using methoxy poly(ethylene glycol)-b-polylactide (mPEG-PLA) block copolymers as drug carriers. The resulting Ps-DOX-CA4P has vesicles shape with uniform sizes of about 50 nm and controlled co-encapsulation ratios of DOX to CA4P. More importantly, Ps-DOX-CA4P (1:10) showed strong synergistic cytotoxicity (combination index CI = 0.31) against human nasopharyngeal epidermal carcinoma (KB) cells. Furthermore, Ps-DOX-CA4P accumulated remarkably in KB tissues xenografts in nude mice. Consistent with these observations, Ps-DOX-CA4P (1:10) achieved significant antitumor potency because of fast tumor vasculature disruption and sustained tumor cells proliferation inhibition in vivo. The overall findings indicate that co-delivery of an antiangiogenic drug and a chemotherapeutic agent in polymersomes is a potentially promising strategy for cancer therapy.

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Ambrosia artemisiifolia is native to North America but has become a worldwide invasive weed. It was introduced to China more than 80 years ago and has spread into 20 provinces since then. To assess the population structure of A. artemisiifolia in China and whether this invasion involved a single event or multiple events, we investigated patterns of genetic variation for three chloroplast DNA intergenic spacer regions, a nrITS region and five microsatellite loci. Our dataset consists of 370 individuals from 19 sites throughout China. We compared their cpDNA-haplotypes to those published for native North American populations. The distribution of cpDNA-haplotypes indicates that A. artemisiifolia was introduced to China multiple times from different source regions. The numbers of alleles in Chinese populations were not significantly lower than in native populations. Both nrITS-haplotypes and microsatellite alleles showed that there was no evidence for a genetic bottleneck. Four populations were genetically well separated from the other 15 populations. However, the absence of isolation by distance, and the low levels of genetic differentiation and gene flow among the other 15 population suggest that most populations in China come from pre-admixed populations. To find the exact source regions of the Chinese populations, more samples from the native region and other invaded regions will be necessary. Nevertheless, our study provides important insights into the genetic background of A. artemisiifolia invasion in China.

5Owing to low therapeutic efficacy and high toxicity associated with conventional single drug chemotherapy, combination therapy has been adopted in clinics. We employed polymer micelles for sequential delivery of resveratrol (RES) and paclitaxel (PTX) to obtain a synergistic anticancer activity. Briefly, PTX and RES co-encapsulated micelles were prepared by thin film method using mPEG-b-PLA block copolymers as carriers with a particle diameter of 20 nm and high encapsulation efficiencies of 95% for both PTX and RES. Furthermore, time-dependent sequential release of two drugs resulted in sensitizing the cancer cells to apoptosis. In vitro cytotoxicity 10 test, the combination strategy exerted synergistic effect (combination index, CI=0.7~0.8) both in the PTX-resistant human lung adenocarcinoma epithelial (A549/T) cell line and mice sarcoma 180 (S180) cells while showing very limited toxicity towards the normal human hepatic (L02) cell strain and normal human kidney (HK-2) cell line, which could be illustrated from manipulating ROS levels by redox modulation and reducing protective autophagy. In vivo, the combination therapy achieved the best antitumor effect in all treatment groups in S180 bearing mice and evoked the most significant changes in the cytoarchitecture leading to tumor regression according to the 15 histological studies. In conclusion, PTX and RES co-encapsulated micelles would provide a potential strategy to selectively treat cancers by inducing ROS-dependent apoptosis and inhibiting autophagy.