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A precisely controlled drug release is a great challenge in exploring methodologies of drug administration and fighting drug resistance for successful cancer chemotherapy. Herein, we developed a dual-mode nanocarrier to specifically deliver doxorubicin (Dox) and precisely control the drug release in target tumor cells. This hierarchical nanocarrier consisted of a gold nanorod as the heating core, biodegradable mesoporous silica as the storage chamber, and graphene quantum dot (GQD) as a drug carrier. The Arg-Gly-Asp peptides on the nanocarrier surface facilitated the specific interaction with integrin-overexpressed tumor cells and subsequent uptake via receptor-mediated endocytosis. Once exposed under the near-infrared (NIR) laser, the internalized nanocarrier rapidly heated the surrounding environment, which led to an instantaneous drug release by collapsing the π-π interaction between Dox and GQDs at high temperature and thereby intensified therapeutic efficacy. On the other hand, the silica shells underwent gradual degradation in the cellular matrix environment, along with stepwise liberation of the embedded GQD-Dox composites from the confined porous structure for the Dox release, exerting a long-term lethality to the tumor cells. By virtue of the physicochemical properties and synergistic behavior of the multiple components in this hierarchical nanocarrier, the NIR-triggered prompt release mode and the biodegradation-mediated slow release mode functioned in a precise and collaborative fashion, providing a promising way to manipulate the pharmacokinetics for precise cancer treatment.

Great challenges in investigating the release of drug in complex cellular microenvironments necessitate the development of stimuli-responsive drug delivery systems with real-time monitoring capability. In this work, a smart drug nanocarrier based on fluorescence resonance energy transfer (FRET) is fabricated by capping graphene quantum dots (GQDs, the acceptor) onto fluorescent mesoporous silica nanoparticles (FMSNs, the donor) via ATP aptamer for real-time monitoring of ATP-triggered drug release. Under extracellular conditions, the fluorescence of FMSNs remains in the "off" state in the low ATP level which is unable to trigger the release of drug. Once specifically recognized and internalized into the target tumor cells by AS1411 aptamer, in the ATP-rich cytoplasm, the conformation switch of the ATP aptamer causes the shedding of the GQDs from the nanocarriers, leading to the release of the loaded drugs and consequently severe cytotoxicity. Simultaneously, the fluorescence of FMSNs turns "on" along with the dissociation of GQDs, which allows real-time monitoring of the release of drug from the pores. Such a drug delivery system features high specificity of dual-target recognition with AS1411 and ATP aptamer as well as high sensitivity of the FRET-based monitoring strategy. Thus, the proposed multifunctional ATP triggered FRET-nanocarriers will find potential applications for versatile drug-release monitoring, efficient drug transport, and targeted cancer therapeutics.

A positive and a negative feedback loop can induce bistability and oscillation, respectively, in biological networks. Nevertheless, they are frequently interlinked to perform more elaborate functions in many gene regulatory networks. Coupled positive and negative feedback loops may exhibit either oscillation or bistability depending on the intensity of the stimulus in some particular networks. It is less understood how the transition between the two dynamic modes is modulated by the positive and negative feedback loops. We developed an abstract model of such systems, largely based on the core p53 pathway, to explore the mechanism for the transformation of dynamic behaviors. Our results show that enhancing the positive feedback may promote or suppress oscillations depending on the strength of both feedback loops. We found that the system oscillates with low amplitudes in response to a moderate stimulus and switches to the on state upon a strong stimulus. When the positive feedback is activated much later than the negative one in response to a strong stimulus, the system exhibits long-term oscillations before switching to the on state. We explain this intriguing phenomenon using quasistatic approximation. Moreover, early switching to the on state may occur when the system starts from a steady state in the absence of stimuli. The interplay between the positive and negative feedback plays a key role in the transitions between oscillation and bistability. Of note, our conclusions should be applicable only to some specific gene regulatory networks, especially the p53 network, in which both oscillation and bistability exist in response to a certain type of stimulus. Our work also underscores the significance of transient dynamics in determining cellular outcome.

A buck/boost supply modulator (BBSM) is proposed for 4G LTE RF power amplifier (RF-PA) envelope tracking applications. The H-bridges used in non-inverting buck/boost converters are metamorphosed into the current sources and switches of a 4-bit current-steering DAC-like supply modulator. Fast tracking speed is achieved through its inherent open-loop topology, while the direct digital interface provides easy control and integration with digital LTE baseband SoCs. The proposed BBSM is capable of delivering peak power of 2.8W at 20MS/s, with a peak efficiency of 75 %.