Drug delivery systems (DDS) with favorable serum stability, high intra-tumor accumulation and tumor specific drug release are highly desired for promoting chemotherapeutic efficacy.

Alveolar Echinococcosis (AE) is a zoonotic parasitic disease caused by Echinococcus multilocularis, but its pathogenesis remains unclear. The primary objective of this study is to explore whether Echinococcus multilocularis protoscoleces (PSCs) regulate macrophage polarization and glucose metabolism by PI3K/Akt/mTOR signaling pathway. We found that large numbers of CD68⁺ macrophages gathered in close liver issue from the lesion in AE patients. PSCs preferentially differentiated into M2 macrophages and the expressions of HK1, PFKL, PKM2, PI3K, Akt, p-Akt, mTOR and p-mTOR increased. The above results show that Echinococcus multilocularis protoscoleces enhance glycolysis to promote M2 macrophages through PI3K/Akt/mTOR signaling pathway.

One of the key steps in tumorigenic transformation is immortalization in which cells bypass cancer-initiating barriers such as senescence. Senescence can be triggered by either telomere erosion or oncogenic stress (oncogene-induced senescence, OIS) and undergo p53- or Rb-dependent cell cycle arrest. The tumor suppressor p53 is mutated in 50% of human cancers. In this study, we generated p53N236S (p53S) mutant knock-in mice and observed that p53S heterozygous mouse embryonic fibroblasts (p53^S/+) escaped HRas^V12-induced senescence after subculture in vitro and formed tumors after subcutaneous injection into severe combined immune deficiency (SCID) mice. We found that p53S increased the level and nuclear translocation of PGC–1α in late-stage p53^S/++Ras cells (LS cells, which bypassed the OIS). The increase in PGC–1α promoted the biosynthesis and function of mitochondria in LS cells by inhibiting senescence-associated reactive oxygen species (ROS) and ROS-induced autophagy. In addition, p53S regulated the interaction between PGC–1α and PPARγ and promoted lipid synthesis, which may indicate an auxiliary pathway for facilitating cell escape from aging. Our results illuminate the mechanisms underlying p53S mutant-regulated senescence bypass and demonstrate the role played by PGC–1α in this process.

Alveolar echinococcosis (AE) is a fatal foodborne parasitic disease caused by the larvae of Echinococcus multilocularis. The disease primarily affects the liver. Previous studies have found that Kupffer cells have an immune protective effect, but in the late stages of AE, they are associated with parasite immune escape. The present study analyzed the effects of Echinococcus multilocularis protoscoleces (PSCs) infection on the mitochondrial morphology and function of macrophages, as well as their phagocytic function and apoptosis. Infection with PSCs has been shown to result in the fragmentation of the macrophage mitochondrial network, the impairment of mitochondrial membrane potential, the elevation of mitochondrial reactive oxygen species, and the reduction in mitochondrial DNA copy number. This cascade of events, consequent to the infection, has been demonstrated to promote the apoptosis of macrophages and impair their phagocytic function. Inhibiting mitochondrial fission during PSCs infection has been shown to mitigate mitochondrial dysfunction, suppress macrophage apoptosis, and enhance macrophage phagocytic function. This discovery provides insights into improving macrophage function during the progression of AE.