The doxorubicin/salinomycin sodium mole ratio of 1:1 had the best synergistic combination index value, and was chosen as the drug ratio in SDLN. SDLN could maintain the drug ratio between 1:1 and 3:1 in 12 h in vivo. SDLN and SLN + DLN showed the best tumor inhibitory rate, and could significantly decrease the percentage of liver cancer stem cells in vivo. SDLN and SLN + DLN may serve as an effective approach to treat liver cancer.

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PurposeLiver cancer is the third leading cause of cancer-related deaths worldwide. Liver cancer stem cells (LCSCs) are a subpopulation of cancer cells that are responsible for the initiation, progression, drug resistance, recurrence, and metastasis of liver cancer. Recent studies have suggested that the eradication of both LCSCs and liver cancer cells is necessary because the conversion of cancer stem cells (CSCs) to cancer cells occasionally occurs. As ATP-binding cassette (ABC) transporters are overexpressed in both CSCs and cancer cells, combined therapies using ABC transporter inhibitors and chemotherapy drugs could show superior therapeutic efficacy in liver cancer. In this study, we developed poly(lactide-co-glycolide)/d-alpha-tocopherol polyethylene glycol 1000 succinate nanoparticles to accomplish the simultaneous delivery of an optimized ratio of doxorubicin (DOX) and elacridar (ELC) to target both LCSCs and liver cancer cells.MethodsMedian-effect analysis was used for screening of DOX and ELC for synergy in liver cancer cells (HepG2 cells) and LCSCs (HepG2 tumor sphere [HepG2-TS]). Then, nanoparticles loaded with DOX and ELC at the optimized ratio (NDEs) were prepared by nanoprecipitation method. The cytotoxicity and colony and tumor sphere formation ability of nanoparticles were investigated in vitro, and the tissue distribution and antitumor activity of nanoparticles were evaluated in vivo.ResultsWe demonstrated that a DOX/ELC molar ratio of 1:1 was synergistic in HepG2 cells and HepG2-TS. NDEs were shown to exhibit significantly increased cytotoxic effects against both HepG2 and HepG2-TS compared with DOX-loaded nanoparticles (NDs) or ELC-loaded nanoparticles (NEs) in vitro. In vivo studies demonstrated that the nanoparticles exhibited better tumor targeting, with NDE showing the strongest antitumor activity with lower systemic toxicity.ConclusionThese results suggested that NDE represented a promising combination therapy against liver cancer by targeting both liver cancer cells and CSCs.

Background:Combined chemotherapy has gradually become one of the conventional methods of cancer treatment due to the limitation of monotherapy. However, combined chemotherapy has several drawbacks that may lead to treatment failure because drug synergy cannot be guaranteed, achievement of the optimal synergistic drug ratio is difficult, and drug uptake into the tumor is inconsistent. Nanomedicine can be a safe and effective form of drug delivery, which may address the problems associated with combination chemotherapy. Objective:This review summarizes the recent research in this area, including the use of nanoparticles, liposomes, lipid-polymer hybrid nanoparticles, and polymeric micelles, and provides new approach for combined chemotherapy. Methods:By collecting and referring to the related literature in recent years. Results:Compared with conventional drugs, nanomedicine has the following advantages: it increases bioavailability of poorly soluble drugs, prolongs drug circulation time in vivo, and permits multiple drug loading, all of which could improve drug efficacy and reduce toxicity. Furthermore, nanomedicine can maintain the synergistic ratio of the drugs; deliver the drugs to the tumor at the same time, such that two or more drugs of tumor treatment achieve synchronization in time and space; and alter the pharmacokinetics and distribution profile in vivo such that these are dependent on nanocarrier properties (rather than being dependent on the drugs themselves). Conclusion:Therefore, nanomedicine-mediated combination drug therapy is promising in the treatment of tumors.

The finite-difference time-domain (FDTD) method adopts the most popular numerical model simulating ground penetrating radar (GPR) wave propagation in an underground structure. However, a staircase approximation method is usually adopted to simulate the curved boundary of an irregular object in the FDTD and symplectic partitioned Runge-Kutta (SPRK) methods. The approximate processing of rectangular mesh parameters will result in calculation errors and virtual surface waves for irregular targets of an underground structure. In this paper, we examine transverse mode (TM) electromagnetic waves with numerical models of electromagnetic wave propagation in geoelectric structures with conformal finite-difference time-domain (CFDTD) method technology in which the effective dielectric parameters are used to accurately simulate the dielectric surface and to absorb waves at the edges of the grid. The third orders of the transmission boundary are used in this paper. Additionally, three complex geocentric models of inclined layered media, spherical media, and three-layered pavement model with structural damages are set up for simulation calculations, then we carry out the actual radar wave detection in a laboratory as the fourth numerical example. Comparison of simulated reflectance waveform of FDTD, symplectic partitioned Runge-Kutta (SPRK), and CFDTD methods shows that at least 50% of the virtual waves can be reduced by using the proposed algorithm. Wiggle diagrams of FDTD and CFDTD methods show that much of the virtual waves have been reduced, and the radar image is clearer than before. This provides a method for the detection of complex geoelectric and layered structures in actual engineering.