Chronic overconsumption of TiO₂NPs-containing foods, such as gum, candy and puddings, is likely to deteriorate the gastrointestinal tract and change the structures of microbiota.

Upconversion nanoparticles (UCNPs) have drawn much attention in biomedicine, and the clinical translation of UCNPs is closely related to their toxicity and metabolism in vivo. In this study, we chose polyethyleneimine modified NaYF₄:Yb,Er upconversion nanoparticles (abbreviated as PEI@UCNPs) to systematically study the biodistribution in mice using intravenous (i.v.), intraperitoneal (i.p.), and intragastric (i.g.) administration. The i.p. injected PEI@UCNPs exhibited obvious accumulation in the spleen within 30 days. Comparably, PEI@UCNPs via i.g. administration exhibited an accumulation that decreased with time in various body tissues and were found mainly in the ileum and cecum but were rather low in concentration in the other examined organs. For the i.v. injected group, the UCNPs exhibited an obvious clearance from the body within 30 days and the accumulation in the spleen gradually decreased. Furthermore, ⁶⁴Cu labeled PEI@UCNPs were i.v. injected for real-time photon emission computed tomography (PET) imaging to further confirm the biodistribution in mice. Afterward, the excretion routes of the PEI@UCNPs were evaluated. For i.p. injected groups, the UCNPs were slowly and partly excreted via feces and urine for 30 days, and a large number of the UCNPs were steadily excreted via feces for the i.v. group, suggesting that the UCNPs via i.v. injection can be potentially used for imaging and therapy studies in vivo. However, for the i.g. administrated group, most of the UCNPs were excreted through feces within 48 h. Hematology, body weight, and biochemical analysis were used to further quantify the potential toxicity of the UCNPs, and results indicated that there was no over toxicity of the UCNPs in mice at the tested period. This work suggests that the clearance and excretion capabilities of PEI@UCNPs are particularly dependent on their administration routes.

Aberrant cell cycle machinery and loss of the CDKN2A tumor suppressor locus make CDK4/6 a potential target in pancreatic ductal adenocarcinoma (PDAC). However, a vast majority of PDAC cases do not harbor a durable response to monotherapy of CDK4/6 inhibitor. Utilizing remote loading to co-encapsulate CDK4/6 inhibitor palbociclib (PAL) and an autophagy inhibitor hydroxychloroquine (HCQ), we demonstrate a ratiometrically designed mesoporous silica nanoformulation with synergistic efficacy in subcutaneous and orthotopic PDAC mouse models. The synergism is attributed to the effective intratumoral buildup of PAL/HCQ, which otherwise exhibit distinctly different circulatory and biodistribution profile. PAL/HCQ co-delivery nanoparticles lead to the most effective shrinkage of PDAC compared to various controls, including free drug mixture. Immunohistochemistry reveals that PAL/HCQ co-delivery nanoparticles trigger anti-apoptotic pathway after repetitive intravenous administrations in mice. When combined with a Bcl inhibitor, the performance of co-delivery nanoparticles is further improved, leading to a long-lasting anti-PDAC effect in vivo.