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In this study, we prepared a smart polymeric vehicle for the hydrophobic drug paclitaxel (PTX) that allowed a maximum steady-state circulation and a fast intracellular release in tumors. PTX was linked to the Janus PEGylated (PEG = poly(ethylene glycol)) peptide dendrimer via an enzyme-sensitive linker glycylphenylalanylleucylglycine tetrapeptide by efficient click reaction, resulting in Janus dendritic prodrug with 20.9% PTX content. The prodrug self-assembled into nanoscale particles with appropriate nanosizes, compact morphology, and negative surface charge. In addition to high stability during circulation, as demonstrated by protein adsorption assays and drug release studies in the cancer’s intracellular environment, the nanoparticles were able to quickly release the drug intact in its original molecular structure, as verified via high-performance liquid chromatography and mass spectrometry analyses. Compared to free PTX, the enzyme-responsive feature of nanoparticles promoted higher cytotoxicity against 4T1 cancer cells and much lower cytotoxicity against normal cells. The nanoparticles accumulated in the tumor and were retained for an extended period of time, as confirmed by fluorescence imaging. Therefore, these nanoparticles exhibited significantly enhanced antitumor efficiency in the 4T1 breast cancer model as indicated by the observed inhibition of angiogenesis and proliferation as well as induction of apoptosis. Moreover, the nanoparticles reduced the occurrence of side effects, particularly dose-limited toxicities, as monitored by body weight and hematological features. Hence, our Janus PEGylated dendrimer-PTX prodrug-based nanoparticles may potentially serve as nanoscale vehicles for breast cancer therapy.

It has been postulated that increased operator workload during task performance may increase fatigue and surgical errors. The National Aeronautics and Space Administration—Task Load Index (NASA-TLX) is a validated tool for self-assessment for workload. Our study aims to assess the relationship of workload and performance of novices in simulated laparoscopic tasks of different complexity levels before and after training. Forty-seven novices without prior laparoscopic experience were recruited in a trial to investigate whether training improves task performance as well as mental workload. The participants were tested on three standard tasks (ring transfer, precision cutting and intracorporeal suturing) in increasing complexity based on the Fundamentals of Laparoscopic Surgery (FLS) curriculum. Following a period of training and rest, participants were tested again. Test scores were computed from time taken and time penalties for precision errors. Test scores and NASA-TLX scores were recorded pre- and post-training and analysed using paired ttests. One-way repeated measures ANOVA was used to analyse differences in NASA-TLX scores between the three tasks. NASA-TLX score was lowest with ring transfer and highest with intracorporeal suturing. This was statistically significant in both pre-training (p< 0.001) and post-training (p< 0.001). NASA-TLX scores mirror the changes in test scores for the three tasks. Workload scores decreased significantly after training for all three tasks (ring transfer = 2.93, p< 0.001, precision cutting = 3.74, p< 0.001, intracorporeal suturing = 2.98, p< 0.001). NASA-TLX score is an accurate reflection of the complexity of simulated laparoscopic tasks in the FLS curriculum. This also correlates with the relationship of test scores between the three tasks. Simulation training improves both performance score and workload score across the tasks.