Colorectal cancer (CRC) is predicted to be the second leading cause of cancer-related death in United States in 2019. Immunotherapies such as checkpoint inhibitors have proven efficacy in patients with high level of microsatellite instability and refractory to routine chemotherapy. Despite this, immunotherapy-based treatment is seriously limited by cancer immunogenicity which has evolved to evade immune surveillance in many circumstances. Efforts are made by researchers using nanoparticles (NPs) to override cancer-mediated immunosuppression, induce immune response against cancer cells or even generate memory immune cells for long-term disease control. These engineered NPs offer great opportunities in delivering cancer immunotherapy due to their unique properties, such as a high drug/antigen loading capacity, adjustable particle size, and versatile surface modification. In this review, we will highlight recent researches on the initiation and development of CRC, the immune microenvironment of CRC, and recent trends in engineering novel NPs-based immunotherapies in the treatment of CRC.

Exploring the mechanism through which berberine (Ber) reverses the multidrug resistance (MDR) of breast cancer is of great importance. Herein, we used the methyl thiazolyl tetrazolium assay to determine the drug resistance and cytotoxicity of Ber and doxorubicin (DOX) alone or in combination on the breast cancer cell line MCF-7/DOX^Fluc. The results showed that Ber could synergistically enhance the inhibitory effect of DOX on tumor cell proliferation in vitro, and the optimal combination ratio was Ber/DOX = 2:1. Using a luciferase reporter assay system combined with the bioluminescence imaging technology, the efflux kinetics of d-luciferin potassium salt in MCF-7/DOX^Fluc cells treated with Ber in vivo was investigated. The results showed that Ber could significantly reduce the efflux of d-luciferin potassium salt in MCF-7/DOX^Fluc cells. In addition, western blot and immunohistochemistry experiments showed that the expression of P-glycoprotein (P-gp/ABCB1) and multidrug resistance protein 1 (MRP1/ABCC1) in MCF-7/DOX^Fluc cells was downregulated upon Ber treatment. Finally, high-performance liquid chromatography was used to investigate the effect of Ber on DOX tissue distribution in vivo, and the results showed that the uptake of DOX in tumor tissues increased significantly when combined with Ber (P < 0.05). Thus, the results illustrated that Ber can reverse MDR by inhibiting the efflux function of ATP-binding cassette transporters and downregulating their expression levels.

A deep insight into the function and kinetics of ATP-binding cassette (ABC) transporters may aid in the development of pharmaceutics that can minimize the particular facet of chemo-resistance. We utilized bioluminescence imaging to monitor the ABC transporter mediated intracellular drug efflux function. We also investigated the potential association between the intracellular bioluminescent pharmacokinetic profiles and the anti-tumor efficacy of the coix seed extract and gemcitabine against pancreatic cancer cells in vitro and in vivo. The bioluminescent pharmacokinetic parameters and pharmacodynamic index (IC₅₀ and TGI) were determined. The expression levels ABCB1 and ABCG2 were assessed. Results showed that coix seed extract could synergistically enhance the anti-cancer efficacy of gemcitabine (p < 0.05). Meanwhile coix seed extract alone or in combination with gemcitabine could significantly increase the AUC_luc while decreasing the K_luc (p < 0.01). Western blot and immunohistochemistry assay demonstrated that coix seed extract could significantly mitigate gemcitabine-induced upregulation of ABCB1 and ABCG2 protein. The Pearson correlation analysis demonstrated that the bioluminescent pharmacokinetic parameters and pharmacodynamic index have strong association in vitro and in vivo. In conclusion coix seed extract could augment the efficacy of gemcitabine therapy in pancreatic cancer cells may at least partly due to the alteration of ABC transporter-mediated drug efflux function.