Co-delivery of paclitaxel and gemcitabine by methoxy poly(ethylene glycol)-poly(lactide-coglycolide)-polypeptide nanoparticles for effective breast cancer therapy.

Traditional chemotherapeutic drugs have shown limited clinical curative effects in antitumor therapy. The application of multidrug combination and adjuvant-drug carriers is a feasible strategy to overcome the limitations while minimizing the dosage of single drug and acquiring the synergistic effects in tumor therapy. However, the systemic toxicity, drug resistance, and tumor recurrence are still unavoidable. Here we develop core-shell nanoparticles (NPs) to encapsulate paclitaxel (PTX) and gemcitabine (GEM) for breast cancer therapy. We find that the NPs could encapsulate PTX and GEM, with an encapsulation efficiency of 96.3 and 95.13%, respectively. Moreover, the drug loading of these NPs is 2.71% (PTX) and 2.64% (GEM). Notably, the co-delivery of GEM and PTX performs enhanced anticancer effect compared with the PTX alone or GEM alone therapy at the same concentration, which indicates a synergistic effect. Moreover, encapsulation of PTX and GEM by methoxy poly(ethylene glycol)-poly(lactide-coglycolide) also shows enhanced anticancer effects (81.5% tumor inhibition) and reduced systemic toxicity in vivo compared with free drugs (65% tumor inhibition). Together with those results, co-delivery of PTX and GEM by methoxy poly(ethylene glycol)-poly(lactide-coglycolide) might have important potencies in clinical applications for breast cancer therapy.

Human exposure levels of PAEs in an e-waste recycling area: Get insight into impacts of spatial variation and manipulation mode.

Phthalic acid esters (PAEs) are one important category of additives in plastics, which are ubiquitous products of e-waste recycling areas, where PAEs are released to the environment intensively and higher exposure level is expected for the employees. This study investigated human exposure levels of PAEs in an e-waste recycling area (Ziya Circular Economy Park (ZCEP) in Tianjin, China) with intending to explore the impacts of residence spatial variation and dismantling manipulation mode. We collected 157 urine samples from three sites around ZCEP with different distances from the core dismantling site and urinary phthalate metabolites (mPAEs) concentrations were measured and were compared among these three sites. The exposure levels of PAEs exhibited spatial variation according to the distance from the core dismantling site, and urinary median ∑mPAEs concentrations (389 ng/mL) of the employees in ZCEP were significantly higher than those of residents in Ziya town (285 ng/mL) and the downtown of Jinghai district (207 ng/mL) (p < 0.05). Moreover, PAEs exposure levels were significantly affected by the manipulation modes in the e-waste recycling area and the urinary median ∑mPAEs concentrations in the employees of family workshops (401 ng/mL) were significantly higher than those in plants with centralized management (298 ng/mL). There were obvious differences on the urinary median mPAEs concentrations between subgroups based on age, BMI, and sex; however, no significant statistical associations were found between PAEs exposure levels and these socio-demographic indices (p > 0.05). Besides, there was no correlation between exposure levels of different PAEs and their physicochemical parameters like the logKow (p > 0.05).