A hybrid bacterium with tumor-associated macrophage polarization for enhanced photothermal-immunotherapy

Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages (TAMs) and increasing the immunogenicity of tumors via immunogenic cell death (ICD) have been emerging as promising anticancer immunotherapy strategies. However, the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging. To overcome these dilemmas, a hybrid bacterium with tumor targeting and penetration, TAM polarization, and photothermal conversion capabilities is developed for improving antitumor immunotherapy in vivo. The hybrid bacteria (B.b@QDs) are prepared by loading Ag2S quantum dots (QDs) on the Bifidobacterium bifidum (B.b) through electrostatic interactions. The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues, enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment. It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photothermal effect of the QDs, resulting in an enhanced immune effect. This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.

Psychotria viridis: Chemical constituents from leaves and biological properties

ABSTRACT The phytochemical study of hexane, chloroform and methanol extracts from leaves of Psychotria viridis resulted in the identification of: the pentacyclic triterpenes, ursolic and oleanolic acid; the steroids, 24-methylene-cycloartanol, stigmasterol and β-sitosterol; the glycosylated steroids 3-O-β-D-glucosyl-β-sitosterol and 3-O-β-D-glucosyl-stigmasterol; a polyunsaturated triterpene, squalene; the esters of glycerol, 1-palmitoylglycerol and triacylglycerol; a mixture of long chain hydrocarbons; the aldehyde nonacosanal; the long chain fat acids hentriacontanoic, hexadecanoic and heptadenoic acid; the ester methyl heptadecanoate; the 4-methyl-epi-quinate and two indole alkaloids, N,N-dimethyltryptamine (DMT) and N-methyltryptamine. The chemical structures were determined by means of spectroscopic (IR, 1H and 13C NMR, HSQC, HMBC and NOESY) and spectrometric (CG-MS and LCMS-ESI-ITTOF) methods. The study of biologic properties of P. viridis consisted in the evaluation of the acetylcholinesterase inhibition and cytotoxic activities. The hexane, chloroform, ethyl acetate and methanol extracts, the substances 24-methylene-cycloartanol, DMT and a mixture of 3-O-β-D-glucosyl-β-sitosterol and 3-O-β-D-glucosyl-stigmasterol showed cholinesterase inhibiting activity. This activity induced by chloroform and ethyl acetate extracts was higher than 90%. The methanol and ethyl acetate extracts inhibit the growth and/or induce the death of the tumor cells strains B16F10 and 4T1, without damaging the integrity of the normal cells BHK and CHO. DMT also demonstrated a marked activity against tumor cell strains B16F10 and 4T1.