Recent advances in the design,development, and targeting mechanisms of polymeric micelles for delivery of siRNA in cancer therapy

Small interfering RNA (siRNA) is a relatively novel nucleic acid-based therapy to treat diseases such as cancer. Nevertheless, substantial obstacles to its clinical applications have been reported, such as low cellular uptake, immunogenicity, off-target effects, and instability in physiological environments. The design of appropriate delivery vehicles capable of transporting siRNA to target cells has been pursued. Nanoparticles are extensively studied for the delivery of siRNA. Among the various nanocarriers, polymeric micelles have recently gained strong interest. Polymeric micelles of average nanometer size are straightforward to design and modify. Hydrophilic groups incorporated in the polymeric micelles can extend in vivo half-life of siRNA to ensure adequate accumulation in tumors, be exchanged for cations that electrostatically interact with siRNA, and be coupled to various ligands for cell-specific targeting. The polymeric micelle core provides stability and serves as a loading dock for drugs. In this review, the different types of polymers used, the design and characterization of polymeric micelles for siRNA delivery, and the established polymeric micelle targeting mechanisms are discussed.     

Ligand-Installed Nanocarriers toward Precision Therapy

Development of drug-delivery systems that selectively target neoplastic cells has been a major goal of nanomedicine. One major strategy for achieving this milestone is to install ligands on the surface of nanocarriers to enhance delivery to target tissues, as well as to enhance internalization of nanocarriers by target cells, which improves accuracy, efficacy, and ultimately enhances patient outcomes. Herein, recent advances regarding the development of ligand-installed nanocarriers are introduced and the effect of their design on biological performance is discussed. Besides academic achievements, progress on ligand-installed nanocarriers in clinical trials is presented, along with the challenges faced by these formulations. Lastly, the future perspectives of ligand-installed nanocarriers are discussed, with particular emphasis on their potential for emerging precision therapies.     

Curcumin based nanomedicines as efficient nanoplatform for treatment of cancer: New developments in reversing cancer drug resistance,rapid internalization,and improved anticancer efficacy

BackgroundCancer is a group of diseases involving an abnormal growth of cells which tend to proliferate in an uncontrolled fashion and in some cases metastasize to the surrounding tissues (malignancy). Resistance to chemotherapy is typically intrinsic (heterogeneity); however, acquired resistance has also become prevelant due to multiple factors including expression of energy-dependent transporters causing expulsion of internalized drug contents extracellular, insensitivity of tumor cells to drug-induced apoptosis, and induction of drug-detoxifying mechanisms. Curcumin (CUR) has gained widespread recognition due to remarkable anticancer, anti-mutagenic, and anti-metastasizing potentials via downregulation of proliferation of cancer cells and induction of apoptosis. Nevertheless, pharmaceutical significance and therapeutic feasibility of CUR is restricted due to intrinsic physicochemical characteristics including poor aqueous solubility, inadequate biological stability, low bioavailability, and short half-life.Scope and approachOwing to these pharmaceutical limitations of CUR, nanodelivery systems have attained remarkable fascination in the recent years. Therefore, this review was aimed to overview and critically ponders recent developments in improving anticancer viability of CUR.Key findings and conclusionCritical analysis of the literature revealed that nanodelivery systems showed promising efficiency in achieving tumor specific targetability, maximizing internalization of drugs into cancer cells, mitigating tumor metastasis, as well as improving anticancer efficacy of CUR. Moreover, nanocarrier-mediated improved pharmacokinetics, drug accumulation, induced promising cytotoxicity, and enhanced anticancer efficacy by suppressing Egr-1 induction, Mitogen-activated protein kinase (MAPK) pathway, and protein tyrosine kinase (PTK) cascades while mitigating the progression of tumor, have also been discussed.     

负性VA-LCD视角特性研究

液晶材料具有双折射效应,因此偏振光在液晶材料中各个方向上发生双折射的程度不同,这决定了LCD的视角特性和对比度随视角的变化有所不同。用光栅光谱仪测量在不同电压驱动下负性VA-LCD的电光特性,以及测量其电光特性随视角的变化;并对其三基色的电光特性和视角特性进行分析。结果表明,三基色的透过率在驱动电压2.2 V之前很小;在2.2 V后,透过率随电压的升高而增大;其中红基色和绿基色的透过率是一直升高,在电压达到5.0 V后,就是趋于平缓,而蓝基色的透过率是在3.7 V左右达到最大,而后慢慢变小,最后在电压达到6.0 V后,趋近一个稳定值。负性VA-LCD三基色的视角特性:红基色的视角范围最宽,绿基色次之,蓝基色的视角范围最窄。     

Improved tumor targetability of Tat-conjugated PAMAM dendrimers as a novel nanosized anti-tumor drug carrier

The generation 4-poly-amidoamine-dendrimers (PAMAM G4 dendrimer, P) was conjugated to Tat peptide (Tat, T), a cell-penetrating peptide, in search of an efficient anti-tumor drug delivery vehicle for cancer therapy. In this study, we synthesized BODIPY-labeled Tat-Conjugated PAMAM dendrimers (BPTs) as a novel nanosized anticancer drug carriers and systemically investigated their biodistribution and the tumor accumulation in Sarcoma 180-bearing mice. In addition, the uptake and the cytotoxicity to S180 cells of BPTs thereof were evaluated. The unmodified dendrimer (BP) showed a soon clearance from the blood stream and nonspecific accumulation in tumor. In contrast, the Tat-modified dendrimer, BPT(64) with appropriate particle size showed a better retention in blood and could be accumulated effectively in tumor tissue via the enhanced permeability and retention (EPR) effect. Moreover, BPTs with a high Tat modification rate was accumulated more effectively in tumor tissue. In vitro experiments, these BPTs displayed low cytotoxicity on S180 cells and high uptake to S180 cells. These findings indicate that the nanoparticulate system on the basis of Tat-conjugated PAMAM dendrimers is safer and effective in the concentration range (below 20?μg/ml) to be used as a carrier of anti-tumor drugs for tumor targeting by intravenous administration.     

耦合时滞光电反馈系统的同步研究

同步是实 现保密通信的基础,现有的基于时滞光电反馈混沌系统的同步研究主要集中在实现方面。本 文利用Lyapunov函数法,从理论研究耦合时滞光电反馈混沌系统的同步问题,包括单向耦合 和双向耦合两种形式。结果表明,耦合时滞光电反馈混沌系统能够实现鲁棒同步。对理论结 果进行了数值实验分析,结果与理论分析相一致。     

Remotely Controlled Red Blood Cell Carriers for Cancer Targeting and Near‐Infrared Light‐Triggered Drug Release in Combined Photothermal–Chemotherapy

Red blood cells (RBCs), the “innate carriers” in blood vessels, are gifted with many unique advantages in drug transportation over synthetic drug delivery systems (DDSs). Herein, a tumor angiogenesis targeting, light stimulus‐responsive, RBC‐based DDS is developed by incorporating various functional components within the RBC platform. An albumin bound near‐infrared (NIR) dye, together with a chemotherapy drug doxorubicin, is encapsulated inside RBCs, the surfaces of which are modified with a targeting peptide to allow cancer targeting. Under stimulation by an external NIR laser, the membrane of the RBCs would be destroyed by the light‐induced photothermal heating, resulting in effective drug release. As a proof of principle, RBC‐based cancer cell targeted drug delivery and light‐controlled drug release is demonstrated in vitro, achieving a marked synergistic therapeutic effect through the combined photothermal–chemotherapy. This work presents a novel design of smart RBC carriers, which are inherently biocompatible, promising for targeted combination therapy of cancer.