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

Abstract

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.

Rifampicin-Loaded Polyelectrolyte Complex Eliminates Intracellular Bacteria through Thiol-Mediated Cellular Uptake and Oxidative Stress Enhancement

“…34, 35 The hemolytic tests and hemagglutination assay were used to evaluate blood compatibility. 32,33 Briefly, 950 μL of PECs solution at different concentrations were mixed with 50 μL of 10% (v/v) red blood cells (RBC) suspension, followed by the 3 h incubation at 37 °C. Saline was set as the negative control, and distilled water was set as the positive control.…”

“…18,30−32 Wang and coworkers reported a cascade-targeting drug delivery system by encapsulating rifampicin in the mannose-decorated poly(α-Nacryloyl-phenylalanine)-block-poly(β-N-acryloyl-D-aminoalanine) nanoparticles. 33 The mannose and D-aminoalanine moieties could sequentially target macrophages and intracellular bacteria, thereby specifically enhancing rifampicin uptake. However, after 24 h incubation with cells, the nanoparticles remained 38% colocalization with lysosomes, which meant unsatisfactory efficiency of cytosolic release.…”

A Coenzyme‐Based Deep Eutectic Supramolecular Polymer Bioadhesive

“…LA has been proved to possess an excellent antioxidant and anti-bacterial function. [11][12][13] However, few of the LA-based materials reported so far have harnessed its bioactive function, since LA monomer is not easily released out in an aqueous environment due to its hydrophobic nature, so the biological activity of LA is greatly sacrificed. [21][22][23] In contrast to this, LA-Na is an amphiphilic molecule with excellent water solubility.…”

“…In light of the excellent antioxidant capacity of LA-based monomers, [11][12][13] the antioxidant effect of the LA-DESP -2 on 1,1diphenyl-2-picrylhydrazyl free radical (DPPH) was detected to evaluate the ROS scavenging activity according to the previously reported protocol. [31,32] As shown in Figure 6d and Figure S21b (Supporting Information), the LA-DESP -2 exhibited a high DPPH clearance efficiency and could achieve 82% scavenging activity after 24 h. Figure S21c (Supporting Information) exhibits the results of naked-eye observation on the decolorization reaction of DPPH reagent with PBS or LA-DESP -2 .…”

“…[10] 𝛼-Lipoic acid (LA), a natural endogenous bio-based small molecule in organisms, participates in mitochondrial activity and regulates energy metabolism. [11][12][13] Since the two adjacent sulfur atoms in its heterocyclic ring repel each other at a high electron cloud density, LA shows a strong reductive property and is considered to be an "omnipotent antioxidant" in redox reaction in human body. [11] Because of its unique biological activity and structural characteristics, LA has been widely applied in nanomedicine for the treatment of diabetes, Alzheimer's disease, and cancer.…”