Single-walled carbon nanotubes (SWCNTs) have been used to deliver single-stranded (ssDNA). ssDNA in oligonucleotide can act as an inhibitor of microRNA to regulate cellular functions. However, these ssDNA are difficult to bind carbon nanotubes with low transferring efficiency to cells. To this end, we designed ssDNA with regulatory and functional units to form ssDNA-SWCNT hybrids to study their binding effects and transferring efficiency. The functional unit on ssDNA mimics the inhibitor (MI) of miRNA-382, which plays a crucial role in the progress of many diseases such as renal interstitial fibrosis. After verification of overexpression of miRNA-382 in a coculture system, we designed oligonucleotide sequences (GCG)5-MI, (TAT)5-MI, and N23-MI as regulatory units added to the 5'-terminal end of the functional DNA fragment, respectively. These regulatory units lead to different secondary structures and thus exhibit different affinity ability to SWCNTs, and finally decide their deliver efficacy to cells. Autophagy, apoptosis and necrosis were observed in renal mesangial cells.
ZIF-8 MOFs, with their large specific surface area and void volume, unique biodegradability and pH sensitivity, and significant loading capacity, have been widely used as carrier materials for bioactive molecules such as drugs, vaccines and genes.
CaCO3 particles, due to their unique properties such as biodegradation, pH-sensitivity, and porous surface, have been widely used as carrier materials for delivering drugs, genes, vaccines, and other bioactive molecules. In these applications, CaCO3 particles are often administered intravenously. In this sense, the interaction between CaCO3 particles and blood components plays a key role in their delivery efficacy and biosafety, though the hemocompatibility of CaCO3 particles has not been evaluated until now. Deficiency in the biosafety information has delayed the clinical use of CaCO3 particles in delivery systems. In this work, we investigated the biosafety of CaCO3 particles, focusing on their in vitro and in vivo effects on key blood components (red blood cells, platelets, etc) and coagulation functions. We found in vitro that high concentrations of CaCO3 particles can cause the aggregation and hemolysis of red blood cells, with platelet activation and coagulation prolongation. In vivo, we found that intravenously injected CaCO3 particles at 50 mg kg−1 significantly disturbed the red blood cells, and platelet-related blood routine indexes, but did not induce visible abnormalities in the tissue structures of the key organs. Overall, these effects may be due to the enormous adsorption capability of the porous surface of CaCO3 particles. 0.1 mg ml−1 of the CaCO3 particles exhibit excellent compatibility for their practical applications. These results would be expected to greatly promote the in vivo applications and clinical use of CaCO3 particles in biomedicine.
Dendritic cells (DCs)-based tumor vaccines have the advantages of high safety and rapid activation of T cells, and have been approved for clinical tumor treatment.However, the conventional DC vaccines have some severe problems, such as poor activation of DCs in vitro, low level of antigen presentation, reduced cell viability, and difficulty in targeting lymph nodes in vivo, resulting in poor clinical therapeutic effects. In this research, magnetic nanoparticles Fe 3 O 4 @Ca/MnCO 3 were prepared and used to actively and efficiently deliver antigens to the cytoplasm of DCs, promote antigen cross-presentation and DC activation, and finally enhance the cellular immune response of DC vaccines. The results show that the magnetic nanoparticles can actively and quickly deliver antigens to the cytoplasm of DCs by regulating the magnetic field, and achieve cross-presentation of antigens. At the same time, the nanoparticles degradation product Mn 2+ enhanced immune stimulation through the interferon gene stimulating protein (STING) pathway, and another degradation product Ca 2+ ultimately promoted cellular immune response by increasing autophagy.The DC vaccine constructed with the magnetic nanoparticles can more effectively migrate to the lymph nodes, promote the proliferation of CD8 + T cells, prolong the time of immune memory, and produce higher antibody levels. Compared with traditional DC vaccines, cytoplasmic antigen delivery with the magnetic nanoparticles provides a new idea for the construction of novel DC vaccines.
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