A Supramolecular “Trident” for Cancer Immunotherapy

Immunotherapy has shown great promise for the treatment of cancer. However, the limited efficacy of single-agent immunotherapy hinders its widespread application, which stimulated the investigation of combination therapy with improved efficacy. Herein, a tri-functional immunostimulatory supramolecular nanomedicine consisting of indoximod (IND, an indoleamine 2,3-dioxygenase (IDO) inhibitor), ^DPPA-1 (a D-peptide antagonist against programmed cell death ligand-1 (PD-L1)), and a self-assembling D-tetrapeptide of G^DF^DF^DY (a powerful adjuvant with immunostimulatory properties) is reported. The resulting IND-G^DF^DF^DY-^DPPA-1 behaves as a supramolecular “trident,” and its three functional parts play parallel roles to boost the effective immune responses. It is shown that the supramolecular “trident” exhibits a stronger binding ability to PD-L1 than the ^DPPA-1 peptide (>fourfold) and is able to inhibit the IDO-1 pathway more efficiently than IND itself. The supramolecular “trident” activates and recruits the cytotoxic CD8⁺ T lymphocytes along with other immune effector cells in tumors, concomitant with downregulation of Foxp3⁺ T cells and upregulation of tumor immune-related cytokines, thus showing a strong ability to improve the tumor microenvironment and enhance immunotherapeutic effects to prevent tumor growth and metastasis in the breast tumor model. The findings may stimulate the development of self-assembling peptide-based multifunctional nanomedicines for cancer therapy.     

Modeling cancer immunotherapy: Assessing the effects of lymphocytes on cancer cell growth and motility

A mesoscopic model is used to describe the effects of lymphocyte activity on a growing tumor. The model yields novel insights into the tumor–immune system interaction. In particular, we found that the presence of a putative chemotactic messenger that helps guide the lymphocytes towards the tumor is not critical to elicit the anti-tumor effects of the immune system, while lymphocytes that block tumor cell migration contribute to limit cancer expansion and thus have a more significant therapeutic impact.     

Quantum phase transition and Coulomb blockade effect in triangular quantum dots with interdot capacitive and tunnel couplings

The quantum phase transition and the electronic transport in a triangular quantum dot system are investigated using the numerical renormalization group method.We concentrate on the interplay between the interdot capacitive coupling V and the interdot tunnel coupling t.For small t,three dots form a local spin doublet.As t increases,due to the competition between V and t,there exist two first-order transitions with phase sequence spin-doublet-magnetic frustration phase-orbital spin singlet.When t is absent,the evolutions of the total charge on the dots and the linear conductance are of the typical Coulomb-blockade features with increasing gate voltage.While for sufficient t,the antiferromagnetic spin correlation between dots is enhanced,and the conductance is strongly suppressed for the bonding state is almost doubly occupied.     

Photon blockade in a cavity-atom optomechanical system

We study the single-photon blockade (1PB), two-photon blockade (2PB), and photon-induced tunneling (PIT) effects in a cavity-atom optomechanical system in which a two-level atom is coupled to a single-model cavity field via a two-photon interaction. By analyzing the eigenenergy spectrum of the system, we obtain a perfect 1PB with a high occupancy probability of single-photon excitation, which means that a high-quality and efficient single-photon source can be generated. However, PIT often occurs in many cases when we consider 2PB in analogy to 1PB. In addition, we find that a 2PB region will present in the optomechanical system, which can be proved by calculating the correlation function of the model analytically.     

A Nanoscale Metal–Organic Framework to Mediate Photodynamic Therapy and Deliver CpG Oligodeoxynucleotides to Enhance Antigen Presentation and Cancer Immunotherapy

Checkpoint blockade immunotherapy (CBI) awakes a host innate immune system and reactivates cytotoxic T cells to elicit durable response in some cancer patients. Now, a cationic nanoscale metal–organic framework, W‐TBP, is used to facilitate tumor antigen presentation by enabling immunogenic photodynamic therapy (PDT) and promoting the maturation of dendritic cells (DCs). Comprised of dinuclear W^VI secondary building units and photosensitizing 5,10,15,20‐tetra(p‐benzoato)porphyrin (TBP) ligands, cationic W‐TBP mediates PDT to release tumor associated antigens and delivers immunostimulatory CpG oligodeoxynucleotides to DCs. The enhanced antigen presentation synergizes with CBI to expand and reinvigorate cytotoxic T cells, leading to superb anticancer efficacy and robust abscopal effects with >97 % tumor regression in a bilateral breast cancer model.     

Signature of Kondo effect in silicon quantum dots

We report observation of the Kondo effect in the Coulomb blockade oscillations of an impurity quantum dot (IQD). This IQD is formed in the channel of a 100 nm gate length Silicon MOSFET. The quantitative analysis of the anomalous temperature and voltage dependence for the drain-source current over a series of Coulomb blockade oscillations is performed. It strongly supports the Kondo explanation for the conductance behavior at very low temperature in this standard microelectronics device. Received 13 November 2001 and Received in final form 18 February 2002     

多岛单电子晶体管的实现及其源漏特性分析

在淀积有纳米间隙栅电极、源电极和漏电极的衬底上生长量子点，制作出多岛结构的单电子晶体管.在77K温度下对源漏特性进行了测试，得到了库仑阻塞特性.并且成功抑制了单岛单电子晶体管中易出现的共隧穿效应，观察到较大的库仑阈值电压.对试验数据进行了分析，阐明了岛的不同结构组态产生的不同输运效果. 关键词： 单电子晶体管 量子点 库仑阻塞     

通过单电子泵实现对单电子运动的控制及其相图分析

介绍了单电子泵的工作原理，讨论了如何利用库仑阻塞和单电子隧穿实现对单电子泵中单个电子运动的控制，从而给出它的相图，并由此得到了单电子泵的一个重要用途，即控制微小电流.指出栅极可能引入的随机电荷对单电子泵的应用并无影响. 关键词： 单电子泵 库仑阻塞 相图     

Spinning microresonator-induced chiral optical transmission

Chiral quantum optics is a new research area in light-matter interaction that depends on the direction of light propagation and offers a new path for the quantum regulation of light-matter interactions. In this paper, we study a spinning Kerr-type microresonator coupled with Λ-type atom ensembles, which are driven in opposite directions to generate asymmetric photon statistics. We find that a photon blockade can only be generated by driving the spinning resonator on right side without driving the spinning microresonator from the left side, resulting in chirality. The coupling strength between system modes can be precisely controlled by adjusting the detuning amount of the atomic pump field. Because of the splitting of the resonant frequency generated by the Fizeau drag, the destructive quantum interference generated in right side drive prevents the nonresonant transition path of state |1,0⟩ to state |2,0⟩. This direction-dependent chiral quantum optics is expected to be applied to chiral optical devices, single-photon sources and nonreciprocal quantum communications.     

A Thermodynamic Approach to Measuring Entropy in a Few-Electron Nanodevice

The entropy of a system gives a powerful insight into its microscopic degrees of freedom; however, standard experimental ways of measuring entropy through heat capacity are hard to apply to nanoscale systems, as they require the measurement of increasingly small amounts of heat. Two alternative entropy measurement methods have been recently proposed for nanodevices: through charge balance measurements and transport properties. We describe a self-consistent thermodynamic framework for applying thermodynamic relations to few-electron nanodevices—small systems, where fluctuations in particle number are significant, whilst highlighting several ongoing misconceptions. We derive a relation (a consequence of a Maxwell relation for small systems), which describes both existing entropy measurement methods as special cases, while also allowing the experimentalist to probe the intermediate regime between them. Finally, we independently prove the applicability of our framework in systems with complex microscopic dynamics—those with many excited states of various degeneracies—from microscopic considerations.