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The entire human population is at risk of infectious diseases worldwide. Thus far, the diagnosis and treatment of human infectious diseases at the molecular and nanoscale levels have been extremely challenging tasks because of the lack of effective probes to identify and recognize biomarkers of pathogens. Oligonucleotide aptamers are a class of small nucleic acid ligands that are composed of single-stranded DNA (ssDNA) or RNA and act as affinity probes or molecular recognition elements for a variety of targets. These aptamers have an exciting potential for diagnose and/or treatment of specific diseases. In this review, we highlight areas where aptamers have been developed as diagnostic and therapeutic agents for both bacterial and viral infectious diseases as well as aptamer-based detection.

Dendritic poly(amidoamine)s (PAMAM)s were introduced into the side chains of disulfide-containing poly(amidoamine)s via repetitive Michael addition and amidation. The bioreducible poly(amidoamine)s grafted with dendritic polyamidoamines showed high buffer capacity, low cytotoxicity and strong DNA binding ability at low N/P ratio. They were able to condense DNA into small sized polycation/DNA complexes, which degraded and released the incorporated DNA under reductive conditions. In comparison to the original disulfide-containing poly(amidoamine) with aminoethyl side chain, the grafting of the bioreducible poly(amidoamine) with dendrimer greatly improved the transfection efficiencies of 293T and HeLa cells with foreign DNA at various N/P ratios. The structure-gene delivery property relations of dendrimer-grafted polycations will provide valuable insight into the design of highly efficient and less toxic polycationic gene carriers.

The expression of IL-17A and programmed death ligand 1 (PDL1) is increased in estrogen receptor-negative breast cancer. IL-17A promotes tumor cell survival and invasiveness and inhibits the antitumor immune response. The PDL1–PD1 (programmed death protein 1) signaling pathway promotes escape from immune surveillance in tumor cells. The pro-tumor properties of IL-17A and PDL1 in various cancers have been previously examined; however, the relationship and roles of IL-17A and PDL1 in ER-negative breast cancer have not been evaluated. Therefore, we assessed whether IL-17A promotes PDL1 expression in tumor cells and whether targeting of IL-17A could inhibit ER-negative breast cancer progression in a murine model. Our study revealed that IL-17A promoted PDL1 expression in human and mouse cells. In the murine cancer model, targeting of IL-17A inhibited PDL1 expression in the tumor microenvironment, decreased the percentage of Treg cells in tumor-infiltrating lymphocytes, and promoted CD4+ and CD8+ T cells to secrete interferon gamma. More importantly, treatment with combined anti-IL-17A and anti-PDL1 antibodies enhanced antitumor effects in favor of tumor eradication. Thus, our study established a pro-tumor role of IL-17A in promoting tumor immune escape and supports the development of a novel cytokine immunotherapy against breast cancer.

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Polyaspartamide-based oligo-ethylenimine brushes (PASP-EDA, PASP-TEPA, PASP-PEHA, and PASP-PEI 423) were synthesized from polysuccinimide (PSI) via a ring-opening reaction with N-Boc protected ethylenediamine, tetraethylenepentamine, pentaethylenehexamine, and linear polyethylenimine (Mn 423), respectively. PASP-TEPA, PASP-PEHA, and PASP-PEI 423 possess high buffer capacity between pH 5 and pH 7, which is comparable to that of branched PEI 25000. The cytotoxicity assay indicated that they all are less toxic than PEI 25000. At an N/P ratio of above 2, all of the four synthetic polycation brushes can condense plasmid DNA to form small sized (160-400 nm) polyelectrolyte complexes with positive surface charge. The transfection of HEK 293 cells with oligo-ethylenimine brush/pRE Luc polyplexes indicated that the transfection efficiencies increased with increasing the length of oligo-ethylenimine side chains. The luciferase expression with PASP-PEHA and PASP-PEI 423 were as high as or even a little higher than that of PEI 25000. The results demonstrate that polyaspartamide-based oligo-ethylenimine brushes are a very promising class of novel polycations for highly efficient and less toxic gene delivery.