Structures and Applications of Nucleic Acid-Based Micelles for Cancer Therapy.

Nucleic acids have become important building blocks in nanotechnology over the last 30 years. DNA and RNA can sequentially build specific nanostructures, resulting in versatile drug delivery systems. Self-assembling amphiphilic nucleic acids, composed of hydrophilic and hydrophobic segments to form micelle structures, have the potential for cancer therapeutics due to their ability to encapsulate hydrophobic agents into their core and position functional groups on the surface. Moreover, DNA or RNA within bio-compatible micelles can function as drugs by themselves. This review introduces and discusses nucleic acid-based spherical micelles from diverse amphiphilic nucleic acids and their applications in cancer therapy.

The Rhetoric of Hydropathy and Lay Medical Agency in Mid-Nineteenth-Century Britain.

This essay examines a neglected archive of hydropathic memoirs to reconstruct the lay experience of seeking medical agency in the full-fledged alternative medical market in mid-nineteenth-century Britain. Two main texts under examination are Edward Bulwer-Lytton's Confessions of a Water Patient (1845) and J. Leech's Three Weeks between Wet Sheets; the Diary and Doings of a Moist Visitor to Malvern (1851). While Bulwer-Lytton's encomium for hydropathy features an invalid subject's journey toward a holistic sense of self-command, Leech's satire undermines this empowerment by exposing the anxieties of navigating the market as a medical consumer. Situating the rhetoric of hydropathy within the context of the medical marketplace, this essay illuminates the ways in which the period's alternative health practices, with their shared vision of self-reliant, natural health, offered consumer options primed for the expression of authentic selfhood and the exercise of medical self-governance.

Suppression of Lung Cancer Malignancy by Micellized siRNA through Cell Cycle Arrest.

UBA6-specific E2 conjugation enzyme 1 (USE1) is frequently overexpressed in lung cancer patients. Moreover, the critical role of USE1 in the progression of human lung cancer is also indicated. As the next step, the authors aim to develop USE1-targeted therapeutic agents based on RNA interference (RNAi). In this study, a lipid-modified DNA carrier, namely U4T, which consists of four consecutive dodec-1-ynyluracil (U) nucleobases to increase the cell permeability of siRNA targeting of USE1 is introduced. The U4Ts aggregate to form micelles, and the USE1-silencing siRNA-incorporated soft spherical nucleic acid aggregate (siSNA) can be created simply through base-pairing with siRNA. Treatment with siSNA is effective in suppressing tumor growth in vivo as well as cell proliferation, migration, and invasion of lung cancer cells. Furthermore, siSNA inhibited tumor cell growth by inducing cell cycle arrest in the G1 phase and apoptosis. Thus, the anti-tumor efficacy of siSNA in lung cancer cell lines and that siSNA possesses effective cell-penetrating ability without using cationic transfection moieties are confirmed. Collectively, these results suggest that siSNA can be applied to the clinical application of RNAi-based therapeutics for lung cancer treatment.

Carrier-free micellar CpG interacting with cell membrane for enhanced immunological treatment of HIV-1.

Unmethylated CpG motifs activate toll-like receptor 9 (TLR9), leading to sequence- and species-specific immune stimulation. Here, we engineered a CpG oligodeoxyribonucleotide (ODN) with multiple hydrophobic moieties, so-called lipid-modified uracil, which resulted in a facile micelle formation of the stimulant. The self-assembled CpG nanostructure (U4CpG) containing the ODN 2216 sequence was characterized by various spectroscopic and microscopic methods together with molecular dynamics simulations. Next, we evaluated the nano-immunostimulant for enhancement of anti-HIV immunity. U4CpG treatment induced activation of plasmacytoid dendritic cells (pDCs) and natural killer (NK) cells in healthy human peripheral blood, which produced type I interferons (IFNs) and IFN-γ in human peripheral blood mononuclear cells (PBMCs). Moreover, we validated the activation and promotion efficacy of U4CpG in patient-derived blood cells, and HIV-1 spread was significantly suppressed by a low dosage of the immunostimulant. Furthermore, U4CpG-treated PBMC cultured medium elicited transcription of latent HIV-1 in U1 cells indicating that U4CpG reversed HIV-1 latency. Thus, the functions of U4CpG in eradicating HIV-1 by enhancing immunity and reversing latency make the material a potential candidate for clinical studies dealing with viral infection.

Soft matter DNA nanoparticles hybridized with CpG motifs and peptide nucleic acids enable immunological treatment of cancer.

Nucleic acids have been used as building blocks to assemble nanostructures by their sequence specific self-recognition properties, and resulting DNA architectures were applied as potential multifunctional drug carriers. Here, we report an amphiphilic lipid-DNA aggregate hybridized with pharmaceutically active DNA and peptide segments for cancer immunotherapy. The facile formulation of the CpG sequence and antigen peptide-bearing peptide nucleic acid representing immune-adjuvant and antigen, respectively, enabled the highly efficacious induction of antigen-specific immune activation. This immunotherapeutic formulation was evaluated in terms of multiple types of tumor growth and metastasis in vivo.

Administration of Soft Matter Lipid-DNA Nanoparticle As the Immunostimulant via Multiple Routes of Injection in Vivo.

We elucidated the proper routes for injecting lipid-DNA micelles formulated with an oligonucleotide immune adjuvant in naïve and tumor-bearing mice. We report herein that after assessing six ways of administering an immunostimulatory nanoparticle (INP), several of the injection routes effectively induced dendritic cell-mediated immune-stimulation in vivo, making them amenable to cancer immunotherapies and vaccines using such DNA materials.

New quantitative method for bone tracer uptake of temporomandibular joint using Tc-99m MDP skull SPECT.

OBJECTIVES: Quantitative bone SPECT studies have several advantages over qualitative studies for evaluating a temporomandibular joint (TMJ), yet in certain cases additional images are still needed. Accordingly, the current study developed a new easy SPECT quantification method for the bone tracer uptake in a TMJ and evaluated its usefulness and inter-observer variability in patients with TMJ pain. METHODS: Sixty-six adult patients (11 males, 55 females) with a mean age of 31 years (range 22-79 years) suffering from TMJ pain were questioned regarding the history of their condition, and then subjected to an oromaxillofacial examination and bone SPECT. New quantitative data for TMJs (TMJ index) were calculated from a formula using TMJ and skull counts. RESULTS: TMJs with spontaneous pain had higher TMJ indices than those without spontaneous pain (8.87 vs. 6.87, P = 0.032). TMJs with mouth-opening pain or palpatory pain also exhibited higher TMJ indices than those without such pains, although the differences were not statistically significant. Positive TMJs, according to a visual SPECT interpretation, had much higher TMJ indices than the negative ones (8.99 vs. 5.37, P < 0.001). The reference skull count, mean TMJ count and TMJ index obtained using the proposed TMJ quantification method demonstrated an excellent correlation based on two independent observers (r = 0.996, r = 0.993 and r = 0.989, respectively; P < 0.001). CONCLUSIONS: The current results indicate that the proposed quantitative TMJ bone SPECT is easy to perform, plus the resulting TMJ index has a lower inter-observer variability, making it an effective TMJ evaluation method for patients with painful TMJs, and especially useful for serial studies.