Delivery of oncolytic adenovirus into the nucleus of tumorigenic cells by tumor microparticles for virotherapy
Source:Biomaterials, Volume 89
Author(s): Li Ran, Xiaohua Tan, Yanchun Li, Huafeng Zhang, Ruihua Ma, Tiantian Ji, Wenqian Dong, Tong Tong, Yuying Liu, Degao Chen, Xiaonan Yin, Xiaoyu Liang, Ke Tang, Jingwei Ma, Yi Zhang, Xuetao Cao, Zhuowei Hu, Xiaofeng Qin, Bo Huang
Oncolytic viruses have been utilized for the treatment of various cancers. However, delivery of the viral particles to tumor cells remains a major challenge. Microparticles (MP) are vesicle forms of plasma membrane fragments of 0.1–1 μm in size that are shed by cells. We have previously shown the delivery of chemotherapeutic drugs using tumor cell-derived MPs (T-MP). Here we report that T-MPs can be utilized as a unique carrier system to deliver oncolytic adenoviruses to human tumors, leading to highly efficient cytolysis of tumor cells needed for in vivo treatment efficacy. This T-MP-mediated oncolytic virotherapy approach holds multiple advantages, including: 1) delivery of oncolytic adenovirus by T-MPs is able to avoid the antiviral effect of host antibodies; 2) delivery of oncolytic adenovirus by T-MPs is not limited by virus-specific receptor that mediates the entry of virus into tumor cells; 3) T-MPs are apt at delivering oncolytic adenoviruses to the nucleus of tumor cells as well as to stem-like tumor-repopulating cells for the desired purpose of killing them. These findings highlight a novel oncolytic adenovirus delivery system with highly promising clinical applications.
DOI: 10.1039/C5CS00499C, Review Article
Understanding the interaction between nanoparticles, blood and blood vessel cells for a better designed of nanomedicine.
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Cancer: A dendritic-cell brake on antitumour immunity
Nature 523, 7560 (2015). doi:10.1038/523294a
Authors: Miriam Merad & Hélène Salmon
Activation of a cellular stress response and the transcription factor XBP1 in dendritic cells has now been shown to limit the cells' ability to stimulate antitumour immune responses in a mouse model of ovarian cancer.
Effects of Delocalized Charge Carriers in Organic Solar Cells: Predicting Nanoscale Device Performance from Morphology
Monte Carlo simulations of charge transport in organic solar cells are performed for ideal and isotropic bulk heterojunction morphologies while altering the delocalization length of charge carriers. Previous device simulations have either treated carriers as point charges or with a highly delocalized mean-field treatment. This new model of charge delocalization leads to weakening of Coulomb interactions and more realistic predicted current and fill factors at moderate delocalization, relative to point charges. It is found that charge delocalization leads to significantly increased likelihood of escaping interface traps. In isotopic two-phase morphologies, increasing the domain sizes leads to slight decreases in predicted device efficiencies. It was previously shown that tortuous pathways in systems with small domain sizes can decrease device performance in thin film systems. However, the diminishing effects of Coulomb interactions with delocalization and efficient separations of excitons by small domains make morphological effects less pronounced. The importance of delocalization, which has largely been ignored in past simulations, as a parameter to consider and optimize when choosing materials for organic solar cells is emphasized.
The effects of charge delocalization on device efficiency is probed using mesoscale Monte Carlo simulations of charge transport in idealized and isotropic two-phase morphologies. Interfacial charge trapping is drastically reduced when Coulomb interactions are weakened through moderate delocalization (1.0–2.0 nm). Morphological differences become less dominant as charges delocalize.
Hexamodal imaging using simple nanoparticles is demonstrated. Porphyrin-phospholipids are used to coat upconversion nanoparticles in order to generate a new biocompatible material. The nanoparticles are characterized in vitro and in vivo for imaging via fluorescence, upconversion, positron emission tomography, computed tomography, Cerenkov luminescence, and photoacoustic tomography.
Light-Responsive Helical Polypeptides Capable of Reducing Toxicity and Unpacking DNA: Toward Nonviral Gene Delivery
Gene delivery vehicles: Helical, cationic polypeptides with light-responsive domains showed potent membrane activity and promoted efficient cellular internalization of DNA (see picture). After transfection, a light trigger induces protecting-group removal to expose anionic carboxylate groups. The reduced cationic charge and helix distortion of the polypeptides result in enhanced DNA unpacking and reduced material toxicity because of the eliminated membrane activity.