Synthesis of a drug delivery vehicle for cancer treatment utilizing DNA-functionalized gold nanoparticles.

The treatment of cancer with chemotherapeutic agents has made great strides in the last few decades but still introduces major systemic side effects. The potent drugs needed to kill cancer cells often cause irreparable damage to otherwise healthy organs leading to further morbidity and mortality. A therapy with intrinsic selective properties and/or an inducible activation has the potential to change the way cancer can be treated. Gold nanoparticles (GNPs) are biocompatible and chemically versatile tools that can be readily functionalized to serve as molecular vehicles. The ability of these particles to strongly absorb light with wavelengths in the therapeutic window combined with the heating effect of surface plasmon resonance makes them uniquely suited for noninvasive heating in biologic applications. Specially designed DNA aptamers have shown their ability to serve as drug carriers through intercalation as well as directly acting as therapeutic agents. By combining these separate molecules a multifaceted drug delivery vehicle can be created with great potential as a selective and controllable treatment for cancer. Oligonucleotide-coated GNPs have been created using spherical GNPs but little work has been reported using gold nanoplates in this way. Using the Diasynth method gold nanoplates were produced to absorb strongly in the therapeutic near infrared (nIR) window. These particles were functionalized with two DNA oligonucleotides: one serving as an intercalation site for doxorubicin, and another, AS1411, serving directly as an anticancer targeting/therapeutic agent. These functional particles were fully synthesized and processed along with confirmation of DNA functionalization and doxorubicin intercalation. Doxorubicin is released via denaturation of the DNA structure into which doxorubicin is intercalated upon the heating of the gold nanoplate well above the DNA melting temperature. This temperature increase, due to light stimulation of surface plasmon resonance, was measured during laser application. Successful release of doxorubicin via laser application was measured with fluorescence measurements providing proof that the doxorubicin was successfully intercalated and released

Gold Nanoplates as Cancer-Targeted Photothermal Actuators for Drug Delivery and Triggered Release

The selective exposure of cancerous tissue to systemically delivered chemotherapeutic agents remains a major challenge facing cancer therapy. To address this question, a near infrared responsive oligonucleotide-coated (AS1411, hairpin, or both) gold nanoplate loaded with doxorubicin is demonstrated to be nontoxic to cells without triggered release, while being acutely toxic to cells after 5 minutes of laser exposure to trigger DOX release. Conjugation of oligonucleotides to the nanoplates is confirmed by an average increase in hydrodynamic diameter of 30.6 nm, an average blue shift of the plasmon resonance peak by 36 nm, and an average −10 mV shift in zeta potential of the particles. DOX loading through intercalation into the hairpin DNA structure is confirmed through fluorescence measurements. For both GNP-Hairpin and GNP-Hairpin-AS1411, ~60% of loaded DOX is released after the first 5 minutes of laser exposure (λ=817 nm), with complete release after two more 5-minute exposures. Preliminary proof of concept is demonstrated in vitro using A549 and MDA-MB-231 cell lines as models for breast and lung cancer, respectively. Exposure of cells to untriggered DOX-loaded conjugate with no laser exposure results in little to no toxicity, while laser-triggered release of DOX causes significant cell death

Trojan Horses

In the videogame Trojan Horse, players are given the task of defending the ancient city of Troy from invading Achaeans, who attack the city both at ground level and by scaling the walls by means of their massive wooden horse. The frontal assault depicted in the game thus bears only passing resemblance to the traditional tale, in which wily Odysseus and a select band of warriors enter and ultimately capture the city by secreting themselves inside the horse. Much work has been done in the genre of what might be called vegan apologetics, the explicit defence of veganism against the attacks of its opponents. In this essay, however, I consider an alternative, complementary tactic, which eschews confrontation in favour of a less direct stratagem

The role of group member affect in the relationship between trust and cooperation

It is widely acknowledged that trust greatly affects work group functioning. Whereas trust may facilitate cooperation, distrust may impede it. Insight into when distrusters may be prompted to cooperate may therefore be of importance. Empirical studies point to several moderators of the effect of trust on cooperation. Unfortunately, these studies largely ignored the potential role of group member affect. Our study shows that group members' affective displays (particularly the activation level of the displays) have a substantial impact on the relationship between trust and cooperation. First, a scenario experiment (n=80) revealed that low trusting individuals were more willing to cooperate when confronted with group members who display high (versus low) activation affective states, whereas for more high trusting individuals cooperation was not contingent on other group members' affective displays. Second, a laboratory experiment (n=78), employing a social dilemma paradigm, replicated these findings and indicated that this effect is explained by the extent to which others are expected to cooperate. The discussion focuses on theoretical implications and managerial ramifications. Our study testifies to the significant role that affect may play in keeping up cooperation in organizations and work groups when trust is withering. © 2009 British Academy of Management