The simultaneous intracellular delivery of multiple types of payloads, such as hydrophobic drugs and nucleic acids, typically requires complex carrier systems. Herein, we demonstrate a self-deliverable form of nucleic acid-drug nanostructure that is composed almost entirely of payload molecules. Upon light activation, the nanostructure sheds the nucleic acid shell, while the core, which consists of prodrug molecules, disintegrates via an irreversible self-immolative process, releasing free drug molecules and small molecule fragments. We demonstrate that the nanostructures exhibit enhanced stability against DNase I compared with free DNA, and that the model drug (camptothecin) released exhibits similar efficacy as free, unmodified drugs toward cancer cells.

Nucleic acids are generally regarded as the payload in gene therapy, often requiring a carrier for intracellular delivery. With the recent discovery that spherical nucleic acids enter cells rapidly, we demonstrate that nucleic acids also have the potential to act as a delivery vehicle. Herein, we report an amphiphilic DNA-paclitaxel conjugate, which forms stable micellar nanoparticles in solution. The nucleic acid component acts as both a therapeutic payload for intracellular gene regulation and the delivery vehicle for the drug component. A bioreductively activated, self-immolative disulfide linker is used to tether the drug, allowing free drug to be released upon cell uptake. We found that the DNA-paclitaxel nanostructures enter cells ∼100 times faster than free DNA, exhibit increased stability against nuclease, and show nearly identical cytotoxicity as free drug. These nanostructures allow one to access a gene target and a drug target using only the payloads themselves, bypassing the need for a cocarrier system.

Herein, we report a class of molecular spherical nucleic acid (SNA) nanostructures. These nano-sized single molecules are synthesized from T polyoctahedral silsesquioxane and buckminsterfullerene C scaffolds, modified with 8 and 12 pendant DNA strands, respectively. These conjugates have different DNA surface densities and thus exhibit different levels of nuclease resistance, cellular uptake, and gene regulation capabilities; the properties displayed by the C SNA conjugate are closer to those of conventional and prototypical gold nanoparticle SNAs. Importantly, the C SNA can serve as a single entity (no transfection agent required) antisense agent to efficiently regulate gene expression. The realization of molecularly pure forms of SNAs will open the door for studying the interactions of such structures with ligands and living cells with a much greater degree of control than the conventional polydisperse forms of SNAs.

BackgroundThe identification of quantitative trait loci (QTLs) that are stable and consistent across multiple environments and populations plays an essential role in marker-assisted selection (MAS). In the present study, we used 28,861 simple sequence repeat (SSR) markers, which included 12,560 Gossypium raimondii (D genome) sequence-based SSR markers to identify polymorphism between two upland cotton strains 0–153 and sGK9708. A total of 851 polymorphic primers were finally selected and used to genotype 196 recombinant inbred lines (RIL) derived from a cross between 0 and 153 and sGK9708 and used to construct a linkage map. The RIL population was evaluated for fiber quality traits in six locations in China for five years. Stable QTLs identified in this intraspecific cross could be used in future cotton breeding program and with fewer obstacles.ResultsThe map covered a distance of 4,110 cM, which represents about 93.2 % of the upland cotton genome, and with an average distance of 5.2 cM between adjacent markers. We identified 165 QTLs for fiber quality traits, of which 47 QTLs were determined to be stable across multiple environments. Most of these QTLs aggregated into clusters with two or more traits. A total of 30 QTL clusters were identified which consisted of 103 QTLs. Sixteen clusters in the At sub-genome comprised 44 QTLs, whereas 14 clusters in the Dt sub-genome that included 59 QTLs for fiber quality were identified. Four chromosomes, including chromosome 4 (c4), c7, c14, and c25 were rich in clusters harboring 5, 4, 5, and 6 clusters respectively. A meta-analysis was performed using Biomercator V4.2 to integrate QTLs from 11 environmental datasets on the RIL populations of the above mentioned parents and previous QTL reports. Among the 165 identified QTLs, 90 were identified as common QTLs, whereas the remaining 75 QTLs were determined to be novel QTLs. The broad sense heritability estimates of fiber quality traits were high for fiber length (0.93), fiber strength (0.92), fiber micronaire (0.85), and fiber uniformity (0.80), but low for fiber elongation (0.27). Meta-clusters on c4, c7, c14 and c25 were identified as stable QTL clusters and were considered more valuable in MAS for the improvement of fiber quality of upland cotton.ConclusionMultiple environmental evaluations of an intraspecific RIL population were conducted to identify stable QTLs. Meta-QTL analyses identified a common chromosomal region that plays an important role in fiber development. Therefore, QTLs identified in the present study are an ideal candidate for MAS in cotton breeding programs to improve fiber quality.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2560-2) contains supplementary material, which is available to authorized users.