Rheumatoid arthritis (RA) is a complicated autoimmune disease. The clinical applications of etanercept (EN), a TNF-α inhibitor, can efficiently halt the development of RA. EN is mainly administrated by subcutaneous injection, which may cause low compliance, side effects, and infection risk. In this study, a hyaluronic acid crosslinked microneedle system (MN) was constructed as the transdermal alternative to deliver EN. We describe the formulation, fabrication, characterization, and transdermal insertion study of MN. In vitro bioactivity of EN was conducted and analyzed by dynamic light scattering and circular dichroism spectrum. In vivo evaluation of MN was studied on adjuvant-induced arthritis mice. The MN possessed sufficient mechanical strength, good biocompatibility, little influence on the bioactivity of EN, and high anti-inflammatory efficacy. This work represents a successful example of delivering macromolecule therapeutic treatment by MN for RA treatment. The transdermal delivery of EN by MN offers a new treatment option for RA patients.

DNA nanostructures prepared by self-assembly possess good stability, high biocompatibility, and low immunogenicity as drug delivery vehicles. In this work, DNA tetrahedron (TD) was constructed and modified with SL2B aptamer (S) and folic acid (F). TD possessed a small diameter (~6 nm) and entered into the nucleus quickly. SL2B aptamer can inhibit cancer cell growth by disturbing vascular endothelial growth factor/Notch signaling pathways. To explore the effect of SL2B number on colorectal cancer inhibition, SL2B multimers (dimer, trimer, and tetramer) were constructed by functionalization of TD with different numbers of SL2B. One SL2B per TD was the most efficient anticancer strategy and showed significantly better anticancer efficacy than SL2B, probably due to the enhanced stability of SL2B by TD. Doxorubicin (DOX) is a potent anticancer agent that can intercalate into DNA double strands. Results showed that TD could facilitate DOX entrance into the nucleus and the intracellular delivery of DOX was further enhanced by functionalization of SL2B and F. DOX-intercalated TD modified with two F and two S (DOX@TD-2F2S) could cause sufficient HT-29 cell inhibition at a much lower DOX concentration. In sum, DOX@TD-2F2S exhibited a synergic anticancer biological effect with chemotherapy and can be a promising strategy for treating colorectal cancer.

Antibiotic-resistant bacteria are becoming a serious threat to public health worldwide. To address this problem, we have developed multifunctional peptide (MFP)-coated silver nanoparticles (MFP@AgNPs) for antibacterial studies. MFPs, which can physically adsorb to AgNPs via electrostatic interactions are comprised of a matrix metalloproteinase (MMP) cleavable sequence (PVGLIG), an antimicrobial peptide (tachyplesin-1), and a target peptide (PGP-PEG). The resulting MFP@AgNPs were characterized by various technologies, including UV-vis spectrophotometry, zeta potential analyzer, circular dichroism (CD) spectroscopy, attenuated total reflection-Fourier-transform infrared spectroscopy (ATR-FTIR), and transmission electron microscopy (TEM). The MIC and MBC were investigated against both Gram-positive bacteria and Gram-negative bacteria. The antibacterial activity in vivo was evaluated on MDR-AB (multidrug-resistant Acinetobacter baumannii) infected mice. We found that MFP@AgNPs exhibited antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria. Compared to bare AgNPs, MFP@AgNPs-1 killed MDR-AB faster and more efficiently. SEM images showed that MFP@AgNPs-1 induced cell disruption via cell membrane damage. In vivo studies further confirmed the enhanced antibacterial activity against MDR-AB infections. The developed MFP@AgNPs-1 reduced the cytotoxicity of AgNPs and enhanced the antibacterial activity against MDR-AB in vitro and in vivo, providing a possible solution against multidrug-resistant bacterial infections.