LCP Nanoparticle for Tumor and Lymph Node Metastasis Imaging

A lipid/calcium/phosphate (LCP) nanoparticle formulation (particle diameter ~25 nm) has previously been developed to delivery siRNA with superior efficiency. In this work, 111In was formulated into LCP nanoparticles to form 111In-LCP for SPECT/CT imaging. With necessary modifications and improvements of the LCP core-washing and surface-coating methods, 111In-LCP grafted with polyethylene glycol exhibited reduced uptake by the mononuclear phagocytic system. SPECT/CT imaging supported performed biodistribution studies, showing clear tumor images with accumulation of 8% or higher injected dose per gram tissue (ID/g) in subcutaneous, human-H460, lung-cancer xenograft and mouse-4T1, breast cancer metastasis models. Both the liver and the spleen accumulated ~20% ID/g. Accumulation in the tumor was limited by the enhanced permeation and retention effect and was independent of the presence of a targeting ligand. A surprisingly high accumulation in the lymph nodes (~70% ID/g) was observed. In the 4T1 lymph node metastasis model, the capability of intravenously injected 111In-LCP to visualize the size-enlarged and tumor-loaded sentinel lymph node was demonstrated. By analyzing the SPECT/CT images taken at different time points, the PK profiles of 111In-LCP in the blood and major organs were determined. The results indicated that the decrement of 111In-LCP blood concentration was not due to excretion, but to tissue penetration, leading to lymphatic accumulation. Larger LCP (diameter ~65 nm) nanoparticles were also prepared for the purpose of comparison. Results indicated that larger LCP achieved slightly lower accumulation in the tumor and lymph nodes, but much higher accumulation in the liver and spleen; thus, larger nanoparticles might not be favorable for imaging purposes. We also demonstrated that LCP with a diameter of ~25 nm were better able to penetrate into tissues, travel in the lymphatic system and preferentially accumulate in the lymph nodes due to 1) small size, 2) a well-PEGylated lipid surface, and 3) a slightly negative surface charge. The ability of ~25 nm LCP to deliver genes to the lymph nodes via IV injection was illustrated by RFP cDNA expression. The results promise the potential use of LCP nanoparticles as formulations for the multifunctional, systemic delivery of both imaging and therapeutic agents to both tumors and lymph nodes.Doctor of Philosoph

Self-Assembled Lipid Nanomedicines for siRNA Tumor Targeting

Lipid-based nanoparticle technology has developed from chemical drug carrier into an efficient multifunctional siRNA tumor targeting delivery system. In this review, we start with an overview of the lipid-based nanomedicine history and the two classes of lipidic vectors for DNA or siRNA delivery. Then we discuss the features of lipid-based nanomedicine that lead to effective tumor targeting and the principles behind. We also discuss nanoparticle surface modification, classes of tumor targeting ligands, and other state-of-the-art strategies for enhancing endosome release primarily focused on lipid-based systems. At the end, we show that multifunctional self-assembled lipid-based nanoparticles could also be versatile delivery vehicles for cancer molecular imaging probes

Flowtable-Free Routing for Data Center Networks: A Software-Defined Approach

The paradigm shift toward SDN has exhibited the following trends: (1) relying on a centralized and more powerful controller to make intelligent decisions, and (2) allowing a set of relatively dumb switches to route packets. Therefore, efficiently looking up the flowtables in forwarding switches to guarantee low latency becomes a critical issue. In this paper, following the similar paradigm, we propose a new routing scheme called KeySet which is flowtable-free and enables constant-time switching at the forwarding switches. Instead of looking up long flowtables, KeySet relies on a residual system to quickly calculate routing paths. A switch only needs to do simple modular arithmetics to obtain a packet's forwarding output port. Moreover, KeySet has a nice fault- tolerant capability because in many cases the controller does not need to update flowtables at switches when a failure occurs. We validate KeySet through extensive simulations by using general as well as Facebook fat-tree topologies. The results show that the KeySet outperforms the KeyFlow scheme [1] by at least 25% in terms of the length of the forwarding label. Moreover, we show that KeySet is very efficient when applied to fat-trees

Multi-Slot Allocation Protocols for Massive IoT Devices with Small-Size Uploading Data

The emergence of Internet of Things applications introduces new challenges such as massive connectivity and small data transmission. In traditional data transmission protocols, an ID (i.e., IP address or MAC address) is usually included in a packet so that its receiver is able to know who sent the packet. However, this introduces the big head-small body problem for light payload. To address this problem, the Hint protocols have been proposed. The main idea is to 'encode' information in a tiny broadcast Hint message that allows devices to 'decode' their transmission slots. Thus, it can significantly reduce transmission and contention overheads. In this letter, we extend eHint to support multi-slot data transmissions. Several efficient protocols are proposed. Our simulation results validate that the protocols can significantly increase the number of successfully transmitted devices, channel utilization, and payload of transmitted devices compared with eHint

How to Reduce Unexpected eMBMS Session Disconnection: Design and Performance Analysis

In 3GPP eMBMS, sometimes sessions will be disconnected unexpectedly due to the miss of session keys. Although rekeying can prevent old users from getting multicast data, it also causes authorized users to miss subsequent data if they miss the key update messages. Thus, re-authentication is needed to obtain lost keys from KMM. We point out this problem in our previous work 1. In this paper, we further propose a new KeySet algorithm, which can pre-issue a number of keys to users when they join eMBMS. The advantage is that a user can still decode multicast data even if it misses some key updates tentatively. However, the cost is that allowing some old users to freely enjoying multicast for some time. In this paper, we quantify the tradeoff and derive the optimal case

eHint: An Efficient Protocol for Uploading Small-Size IoT Data

IoT (Internet of Things) has attracted a lot of attention recently. IoT devices need to report their data or status to base stations at various frequencies. The IoT communications observed by a base station normally exhibit the following characteristics: (1) massively connected, (2) lightly loaded per packet, and (3) periodical or at least mostly predictable. The current design principals of communication networks, when applied to IoT scenarios, however, do not fit well to these requirements. When a large number of devices contend to send small packets, the signaling overhead is not cost-effective. To address this problem, our previous work [1] proposes the Hint protocol, which is slot-based and schedule- oriented for uploading IoT devices' data. In this work, we extend [1] to support data transmissions for multiple resource blocks. We assume that the uplink payloads from IoT devices are small, each taking very few slots (or resource blocks), but devices are massive. The main idea is to "encode" information in a tiny broadcast that allows each device to "decode" its transmission slots, thus significantly reducing transmission overheads and contention overheads. Our simulation results verify that the protocol can significantly increase channel utilization compared with traditional schemes

Design and Analysis of the Key Management Mechanism in Evolved Multimedia Broadcast/Multicast Service

3GPP introduced the key management mechanism (KMM) in evolved multimedia broadcast/multicast service (eMBMS) to provide forward security and backward security for multicast contents. In this paper, we point out that KMM may lead to frequent rekeying and re-authentication issues due to eMBMS's characteristics: 1) massive group members; 2) dynamic group topology; and 3) unexpected wireless disconnections. Such issues expose extra load for both user equipment (UE) terminals and mobile operators. It seems prolonging the rekeying interval is an intuitive solution to minimizing the impact of the issues. However, a long rekeying interval is not considered the best operational solution due to revenue loss of content providers. This paper quantifies the tradeoff between the load of the UEs and the operators as well as the revenue loss of the content providers. Moreover, we emphasize how essential this rekeying interval has impacts on the problems. Using our proposed tradeoff model, the operators can specify a suitable rekeying interval to best balance the interest between the above three parties. The tradeoff model is validated by extensive simulations and is demonstrated to be an effective approach for the tradeoff analysis and optimization on eMBMS