Aspirin-Loaded Cross-Linked Lipoic Acid Nanodrug Prevents Postoperative Tumor Recurrence by Residual Cancer Cell Killing and Inflammatory Microenvironment Improvement.

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 anti-inflammatory 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.

Artificial Organelles Based on Cross-Linked Zwitterionic Vesicles.

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.

An oligomeric hyaluronic acid-GX1 molecular target drug with polyvalent targeting to CD44 and VEGF receptors.

The off-target toxicity of molecular targeted drug hinders its clinical transformation. Herein, we report a new molecular targeted drug oHA-GX1 constructed by oligomeric hyaluronan (oHA) and peptide GX1 (CGNSNPKSC). The oHA-GX1 can not only suppress the tumor growth by interacting with overexpressed VEGF and CD44 receptors inside tumor tissues, but also reduce the likelihood of off-target toxicity due to the multiple VEGF and CD44 receptors binding sites. The cytotoxicity study shows that the IC50oHA-GX1 against co-SGC-7901 and co-HUVEC cells fell in the range of common cytotoxic drugs. The animal experiment results reveal that the tumor inhibition rate of oHA-GX1 (100 mg/kg) against SGC-7901 tumor-bearing mice were 78.4 %, which was comparable to that of front-line chemotherapy drugs. Also, the cytotoxicity study on normal cells, hemolysis test, hemagglutination assay and the acute toxicity test demonstrate that oHA-GX1 exhibited excellent biosafety. This molecular targeted drug that utilizes the multiple receptor-binding sites to get rid of the side effects caused by off-target paves a new direction for the discovery of anticancer drugs with high efficacy and low adverse effects.