Artificial
organelles (AOs) are typical microcompartments with
intracellular biocatalytic activity aimed to replace missing or lost
cellular functions. Currently, liposomes or polymersomes are popular
microcompartments to build AOs by embedding channel proteins in their
hydrophobic domain and entrapping natural enzymes in their cavity.
Herein, a new microcompartment is established by using monolayer cross-linked
zwitterionic vesicles (cZVs) with a carboxylic acid saturated cavity.
The monolayer structure endows the cZVs with intrinsic permeability;
the cavity supplies the cZVs ability of in situ synthesis
of artificial enzymes, and the pH-dependent charge-change property
makes it possible to overcome the biological barriers. Typically,
nanozymes of CeO2 and Pt NPs were synthesized in the cZVs
to mimic peroxisome. In vitro experiments confirmed
that the resulting artificial peroxisome (AP) could resist protein
adsorption, endocytose efficiently, and escape from the lysosome. In vivo experiments demonstrated that the APs held a good
therapeutic effect in ROS-induced ear-inflammation.
Featuring the dendrimer-like properties, the cross-linked small-molecule micelles (cSMs) have been shown to be a good alternative to dendrimers in many applications. Following this trend, herein the copper(I)-chelated cross-linked cyclen micelles (Cu I @cCMs) were created as a nanocatalyst for azide-alkyne cycloaddition. Both alkynes and azides with diverse structures performed with excellent reactivity in water at the parts-per-million (ppm) catalyst usage. Recycle experiments disclosed that the nanocatalyst had only slight decrease of catalytic efficiency after reusing many times. Importantly, the Cu I @cCMs could easily enter cells and carry out the intracellular catalysis for lighting up and/or killing cancer cells.
In addition to residual cancer cells, the surgery resection-induced hyperinflammatory microenvironment is a key factor that leads to postsurgical cancer recurrence. Herein, we developed a dual-functional nanodrug Asp@cLANVs for postsurgical recurrence inhibition by loading the classical antiinflammatory drug aspirin (Asp) into cross-linked lipoic acid nanovesicles (cLANVs). The Asp@cLANVs can not only kill residual cancer cells at the doses comparable to common cytotoxic drugs by synergistic interaction between Asp and cLANVs, but also improve the postsurgical inflammatory microenvironment by their strongly synergistic anti-inflammation activity between Asp and cLANVs. Using mice bearing partially removed NCI-H460 tumors, we found that Asp@cLANVs gave a much lower recurrence rate (33.3%) compared with the first-line cytotoxic drug cisplatin (100%), and no mice died for at least 60 days after Asp@cLANV treatment while no mouse survived beyond day 43 in the cisplatin group. This dual-functional nanodrug constructs the first example that combines residual cancer cell killing and postoperative inflammation microenvironment improvement to suppress postsurgical cancer recurrence.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.