Rapid detection and destruction of squamous cell carcinoma of the head and neck by nano‐quadrapeutics

Survival and quality of life remain poor for patients with head and neck squamous cell carcinoma (HNSCC) that cannot be fully resected safely, and form therapy‐resistant residual and recurrent tumors. We report novel cell‐level technology, quadrapeutics. Quadrapeutics converts surgery, drug, and radiation therapies into on‐demand microtreatment that unites the diagnosis and treatment in 1 rapid procedure by using 4 standard components: (1) targeted gold colloids; (2) liposomal drugs; (3) a laser pulse; and (4) radiation, all at safe doses. The therapeutic strength of quadrapeutics increases with cancer aggressiveness. In animal models of a primary and microscopic residual HNSCC, quadrapeutics increased the efficacy of standard chemoradiation therapy by more than 17‐fold by using only 3% to 6% of clinical doses of drug and radiation, did not cause side effects, and detected residual microtumors in vivo intraoperatively. Quadrapeutics can be applied to detect and eradicate HNSCC and similar microtumors in a safe and rapid theranostic procedure. © 2015 Wiley Periodicals, Inc. Head Neck 37: 1547–1555, 2015     

Evaporation-induced cavitation in nanofluidic channels

Cavitation, known as the formation of vapor bubbles when liquids are under tension, is of great interest both in condensed matter science as well as in diverse applications such as botany, hydraulic engineering, and medicine. Although widely studied in bulk and microscale-confined liquids, cavitation in the nanoscale is generally believed to be energetically unfavorable and has never been experimentally demonstrated. Here we report evaporation-induced cavitation in water-filled hydrophilic nanochannels under enormous negative pressures up to -7 MPa. As opposed to receding menisci observed in microchannel evaporation, the menisci in nanochannels are pinned at the entrance while vapor bubbles form and expand inside. Evaporation in the channels is found to be aided by advective liquid transport, which leads to an evaporation rate that is an order of magnitude higher than that governed by Fickian vapor diffusion in macro- and microscale evaporation. The vapor bubbles also exhibit unusual motion as well as translational stability and symmetry, which occur because of a balance between two competing mass fluxes driven by thermocapillarity and evaporation. Our studies expand our understanding of cavitation and provide new insights for phase-change phenomena at the nanoscale.     

Cell-penetrating peptide-doxorubicin conjugate loaded NGR-modified nanobubbles for ultrasound triggered drug delivery

A new drug-targeting system for CD13⁺ tumors has been developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, the CPP-doxorubicin conjugate (CPP-DOX) was entrapped in the asparagine–glycine–arginine (NGR) peptide modified NB (CPP-DOX/NGR-NB) and the penetration of CPP-DOX was temporally masked; local ultrasound stimulation could trigger the CPP-DOX release from NB and activate its penetration. The CPP-DOX/NGR-NBs had particle sizes of about 200?nm and drug entrapment efficiency larger than 90%. In vitro release results showed that over 85% of the encapsulated DOX or CPP-DOX would release from NBs in the presence of ultrasound, while less than 1.5% of that (30?min) without ultrasound. Cell experiments showed the higher cellular CPP-DOX uptake of CPP-DOX/NGR-NB among the various NB formulations in Human fibrosarcoma cells (HT-1080, CD13⁺). The CPP-DOX/NGR-NB with ultrasound treatment exhibited an increased cytotoxic activity than the one without ultrasound. In nude mice xenograft of HT-1080 cells, CPP-DOX/NGR-NB with ultrasound showed a higher tumor inhibition effect (3.1% of T/C%, day 24), longer median survival time (50 days) and excellent body safety compared with the normal DOX injection group. These results indicate that the constructed vesicle would be a promising drug delivery system for specific cancer treatment.     

Ultrasound-responsive nanobubbles contained with peptide–camptothecin conjugates for targeted drug delivery

To improve the targeting delivery efficiency of anticancer drug to tumor sites, a new strategy combining cell-permeable peptide (CPP) and ultrasound was reported in this article. In this study, we devised and tested a strategy for functional payload delivery to cells by loading CPP–camptothecin conjugate (CPP–CPT) into nanobubble (CPP–CPT?NB). Here, CPP existing in the conjugation form of CPP and CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile, local tumor ultrasound was utilized to achieve specific targeting of CPP–CPT to the tumor cells. The mean particle size of the prepared CPP–CPT?NB was ～200?nm, and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90% of the entrapped CPP–CPTs would release from the nanobubbles. Subsequent research demonstrated that the CPP–CPT?NB showed effective cellular uptake and significant cytotoxic activity in HeLa cells in vitro. Additionally, after systemic administration in mice, CPP–CPT?NB with ultrasound showed a higher tumor inhibition effect in nude mice xenografted HeLa cells tumors and excellent body safety when compared with normal CPT injection group. In conclusion, the carrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment.     

Topical oxygen therapy & micro/nanobubbles: a new modality for tissue oxygen delivery

Up to 15 billion dollars of US health care expenditure each year is consumed by treatment of poorly healing wounds whose etiologies are often associated with aberrancies in tissue oxygenation. To address this issue, several modes of tissue oxygen delivery systems exist, including Hyperbaric Oxygen Therapy (HBOT) and Topical Oxygen Therapy (TOT), but their efficacies have yet to be fully substantiated. Micro/nanobubbles (MNBs), which range anywhere from 100 μm to <1 μm in diameter and are relatively stable for hours, offer a new mode of oxygen delivery to wounds. The aim of this article is to systematically review literature examining the use of TOT for wound healing and use of MNBs for tissue oxygenation using the MEDLINE database. The search yielded 87 articles (12 MNB articles and 75 TOT articles), of which 52 met the inclusion criteria for this literature review (12 MNB articles and 40 TOT articles). Additionally, we present an analysis on the efficacy of our MNB generating technology and propose its use as a wound healing agent.     

Activated drying in hydrophobic nanopores and the line tension of water

We study the slow dynamics of water evaporation out of hydrophobic cavities by using model porous silica materials grafted with octylsilanes. The cylindrical pores are monodisperse, with a radius in the range of 1–2 nm. Liquid water penetrates in the nanopores at high pressure and empties the pores when the pressure is lowered. The drying pressure exhibits a logarithmic growth as a function of the driving rate over more than three decades, showing the thermally activated nucleation of vapor bubbles. We find that the slow dynamics and the critical volume of the vapor nucleus are quantitatively described by the classical theory of capillarity without adjustable parameter. However, classical capillarity utterly overestimates the critical bubble energy. We discuss the possible influence of surface heterogeneities, long-range interactions, and high-curvature effects, and we show that a classical theory can describe vapor nucleation provided that a negative line tension is taken into account. The drying pressure then provides a determination of this line tension with much higher precision than currently available methods. We find consistent values of the order of −30 pN in a variety of hydrophobic materials.     

超声纳米微泡造影剂在肿瘤诊疗中的研究进展

随着分子生物学的快速发展,超声纳米微泡造影剂已成为研究热点之一。其作为一种新型的造影剂具有纳米级粒径,在成像方面有多种优势,容易实现对肿瘤的靶向性,在肿瘤诊疗中有一定意义。超声纳米微泡造影剂不仅可以结合超声成像、荧光探针及铁粒子等增强成像效果,还可以包裹肿瘤靶向药物进行药物靶向递送、作为载体和免疫增强剂携载目的基因进行基因转染、促进肿瘤的免疫治疗,为肿瘤的诊断和治疗提供了新方法。本文针对超声纳米微泡造影剂在肿瘤中的研究进展进行综述。     

Dentin Conditioning Protocol for Regenerative Endodontic Procedures

IntroductionThis study focused on the optimization of sodium hypochlorite–EDTA irrigation in terms of the viability and morphology of dental pulp stem cells (DPSCs) and the effects of an optimized EDTA protocol alone or prepared with nanobubble (NB) water on cell behavior.MethodsIn the first part, human dentin discs were conditioned with the following protocols:(1) Sodium hypochlorite followed by phosphate-buffered saline (PBS),(2) Irrigation protocol from group 1 followed by EDTA,(3) Irrigation protocol from group 2 followed by PBS,(4) Sodium hypochlorite followed by EDTA,(5) Irrigation protocol from group 4 followed by PBS. DPSC viability and morphology were determined. In the second part, dentin discs were conditioned with the (1) optimized protocol in the first part, (2) EDTA prepared using NB water, (3) ultrasonic-activated EDTA, or (4) ultrasonic-activated EDTA prepared using NB water. Transforming growth factor beta release and DPSC viability, morphology, and migration were determined using the enzyme-linked immunosorbent assay, the water-soluble tetrazolium salt-1 cell viability assay and live-dead assay, and the transwell migration assay, respectively. Data were analyzed using Kruskal-Wallis or one-way analysis of variance and post hoc tests.ResultsThe highest cell viability was observed in group 3 followed by group 5 (P < .05) in which PBS was used as a final rinse. Irrigation protocol from group 3 was used for the subsequent experiments. Ultrasonic-activated EDTA improved transforming growth factor beta release, viability, and migration of the cells compared with EDTA (P < .05). The preparation of EDTA with NBs did not change the biological properties of the EDTA-conditioned dentin (P > .05).ConclusionsRemoving the residual EDTA using PBS improved the cell viability on the dentin surface. Ultrasonic activation enhanced the growth factor release and biological properties, whereas the preparation of EDTA with NBs showed a similar effect to regular EDTA without compromising the cellular effect.     

多西他赛纳米泡的制备和性质

目的：优化多西他赛（docetaxel,DTX）纳米泡处方和工艺,并考察其性质。方法用Langmuir膜天平筛选成膜材料单甲氧基聚乙二醇-聚（乳酸羟基乙酸）共聚物（mPEG-PLGA）与不同膜稳定剂的最佳比例。以沸点为29.5℃的全氟戊烷为有机相,采用注入法制备mPEG-PLGA包裹DTX的纳米胶束,加入全氟戊烷后可形成纳米乳。考察纳米乳的处方工艺、及其形成纳米泡的条件。采用MTT法考察DTX纳米泡的MCF-7细胞毒性。结果成膜材料最佳比例为mPEG-PLGA∶司盘20=10∶1（摩尔比）,形成的膜弹性好,可耐受温度和超声。DTX纳米泡有明显的温度和超声敏感性。随温度升高粒径逐渐增大;温度降低粒径减小。在超声作用下,纳米泡先发生合并,粒径变大,随后略有减小。DTX纳米泡有显著的MCF-7细胞毒作用,呈剂量依赖性。结论 DTX纳米泡有望成为肿瘤靶向超声触发释药新制剂。