Cancer cell membrane-derived nanoparticles block the expression of immune checkpoint proteins on cancer cells and coordinate modulatory activity on immunosuppressive macrophages.

Cancer is the most recurrent chronic disease in the world, with human hepatocellular carcinoma (HCC) being the second leading cause of death among neoplasias. The high frequency of HCC relapse and metastasis warrants the development of new diagnostic and therapeutic procedures. In advanced stages, neoplastic cells can evade immune surveillance and express immunosuppressive proteins and cytokines at tumor sites. Nanocomposites conjugated with immunomodulatory agents can increase the main mechanisms of cellular immunity. In this study, we used nanocarriers to transport oligonucleotide sequences (siRNAs) into cancer cells and leukocytes to modulate the activity of tumor microenvironment cells in vitro. Cell membrane-derived nanoparticles (MNPs) were synthesized with lipids and proteins from the plasma membrane of hepatic tumor cells to deliver a large amount of antigenic material to professional antigen-presenting cells (APCs), following their exposure to HCC and immunosuppressive macrophages. To establish a pro-inflammatory response, pure lipid MNPs were incorporated with monophosphoryl lipid A and siRNA to silence the c-MYC (myelocytomatosis) oncogene. Nanocarriers were tested for the following: (a) NP internalization into cancer and immunocompetent cells; (b) immunomodulatory activity by observing the expression of cell surface markers; and (c) in vitro cytotoxicity. The adsorption of plasma proteins on the MNPs surface and their effects on cellular uptake were also investigated. Our results indicate that the nanostructures are stable in biological suspensions, and can reduce CD47 and PD-L1 expression on cancer cells and simultaneously switch APC activity for an anti-tumor response.

Toxicity of gold nanorods on Ceriodaphnia dubia and Danio rerio after sub-lethal exposure and recovery.

Gold nanorods (AuNRs) are rod-shaped nanoparticles (NPs) with special optical properties that allow their application in several areas including photothermal therapy, diagnosis, drug and gene delivery, cellular imaging, and biosensors. Their high potential for many applications increases the possibility of release in aquatic environments, which can cause risks to organisms. In this study, we evaluated toxic effects of AuNRs on cladoceran and fish (Ceriodaphnia dubia and Danio rerio) and their recovery after post-exposure periods. The EC50 of 0.03 mg L-1 was found for C. dubia in the acute exposure. There was a significant decrease in the number of neonates produced and in the filtration rate of C. dubia after sub-lethal exposure to AuNRs. The toxic mechanism of these NPs to cladocerans was attributed to increases in the reactive oxygen species (ROS) generation. After 4 h of recovery in clean medium, C. dubia were able to reestablish the filtration rate. Enzymatic biomarkers for D. rerio showed significant increases in the activity of superoxide dismutase, catalase, and lipid peroxidation after sub-lethal exposure to AuNRs. These biomarkers were recovered after 168 h in clean water. These results are pivotal on the comprehension of AuNR toxicity to aquatic organisms and are useful in assessing this novel nanomaterial impacts on aquatic biota.

Differences in the Aspect Ratio of Gold Nanorods that Induce Defects in Cell Membrane Models.

Understanding the interactions between biomolecules and nanomaterials is of great importance for many areas of nanomedicine and bioapplications. Although studies in this area have been performed, the interactions between cell membranes and nanoparticles are not fully understood. Here, we investigate the interactions that occur between the Langmuir monolayers of dipalmitoylphosphatidyl glycerol (DPPG) and dipalmitoylphosphatidyl choline (DPPC) with gold nanorods (NR)-with three aspect ratios-and gold nanoparticles. Our results showed that the aspect ratio of the NRs influenced the interactions with both monolayers, which suggest that the physical morphology and electrostatic forces govern the interactions in the DPPG-NR system, whereas the van der Waals interactions are predominant in the DPPC-NR systems. Size influences the expansion isotherms in both systems, but the lipid tails remain conformationally ordered upon expansion, which suggests phase separation between the lipids and nanomaterials at the interface. The coexistence of lipid and NP regions affects the elasticity of the monolayer. When there is coexistence between two phases, the elasticity does not reflect the lipid packaging state but depends on the elasticity of the NP islands. Therefore, the results corroborate that nanomaterials influence the packing and the phase behavior of the mimetic cell membranes. For this reason, developing a methodology to understand the membrane-nanomaterial interactions is of great importance.