Cationic nanocarrier mediated intracellular therapeutic agent delivery acts as a double-edged sword: the carriers promote cellular uptake, but interact nonspecifically and strongly with negatively charged endogenic proteins and cell membranes, which results in aggregates and high cytotoxicity. The present study was aimed at exploring zwitterionic polyaspartamide derivative nanoparticles for efficient intracellular delivery with low cytotoxicity. Poly(aspartic acid) partially grafted tetraethylenepentamine (PASP-pg-TEPA) with different isoelectric points (IEPs) was synthesized. The PASP-pg-TEPA formed zwitterionic nanoparticles with an irregular core and a well-defined shell structure in aqueous medium. Their particle size decreased from about 300 to 80 nm with an increase of the IEP from 7.5 to 9.1. The surface charge of the PASP-pg-TEPA nanoparticles could be tuned from positive to negative with a change of the pH of the medium. The nanoparticles with an IEP above 8.5 exhibited good stability under simulated physiological conditions. It was noted that the zwitterionic PASP-pg-TEPA nanoparticles displayed highly efficient cellular uptake in HeLa cells (approximately 99%) in serum-containing medium and did not adversely affect the cell viability at concentrations up to 1 mg/mL. Furthermore, thermodynamic analysis using isothermal titration calorimetry provided direct evidence that these zwitterionic nanoparticles had low binding affinities for serum protein. Therefore, the zwitterionic PASP-pg-TEPA nanoparticles could overcome limitations of cationic nanocarriers and achieve efficient intracellular delivery with low cytotoxicity.

This study aims to explore the effect of oxycodone hydrochloride injection on the immune function of patients who underwent radical resection of rectal cancer under general anesthesia.Eighty patients were enrolled and randomly divided into group A and B (n = 40, each). All patients underwent general intravenous anesthesia. At the end of surgery, each patient in group A was injected with 5 mg (5 mL) of oxycodone hydrochloride, while 5 mg (5 mL) of morphine hydrochloride in group B. Venous blood was withdrawn in both groups at different time points. Changes in the numbers of T lymphocyte subsets and natural killer (NK) cells were determined by flow cytometry.First the numbers of T lymphocyte subsets and NK cells at T1, T2, T3, and T4 decreased in both groups, compared with those at T0, and the differences were statistically significant. Furthermore, the numbers reduced to a minimum at T2 and began to recover at T3. Second the differences between group A and B at T1, T2, T3, and T4 were statistically significant; and the numbers of T lymphocytes and NK cells were higher in group A than in group B at corresponding time points.Oxycodone hydrochloride and morphine hydrochloride both have inhibitory effects on immune function in patients undergoing radical resection of rectal cancer after surgery. However, oxycodone hydrochloride has a smaller effect compared to morphine hydrochloride.

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