Supramolecular Induction of Mitochondrial Aggregation and Fusion

Abstract

Mitochondrial fission is often associated with the development of oxidative stress related diseases, as the fragmentation of mitochondria undermines their membranes, advances production of reactive oxygen species, and promotes apoptosis. Therefore, induction of mitochondrial aggregation and fusion could potentially reverse such medical conditions. Herein, a supramolecular strategy to induce mitochondrial aggregation and fusion is developed for the first time. A polyethylene glycol (PEG) system that was dually tagged with triphenylphosphonium (TPP) and adamantane (ADA), namely TPP-PEG-ADA, was designed to target mitochondria and functionalize their surfaces with ADA. Thereafter, the addition of cucurbit[7]­uril (CB[7]) grafted hyaluronic acid (HA) induced supramolecular aggregation and fusion of mitochondria, via strong host–guest interactions between the CB[7] moiety of CB[7]-HA and ADA residing on the surface of mitochondria. As a proof-of-principle, chemically stressed SH-SY5Y cells and zebrafish neurons were effectively protected via this supramolecular mitochondrial fusion strategy in vitro and in vivo, respectively. This study may open up new venues in not only fundamentally controlling mitochondrial dynamics but also addressing the medical needs to treat diseases associated with mitochondrial fission and fragmentation.

Mitochondrion-targeted supramolecular “nano-boat” simultaneously inhibiting dual energy metabolism for tumor selective and synergistic chemo-radiotherapy

“…The results in Figures 2 F, S13 and S14 suggested the supramolecular “nano-boat” could significantly boost the production of ROS in MCF-7 cells, whereas it barely promoted that in L929 cells compared to the effect of the free drug. It is well known that mitochondria are the main provenance of excessive cellular ROS upon exogenous stimulation 49 . Hence, the large ROS in cancer cells probably originated from the mitochondrial impairment and dysfunction caused by the supramolecular “nano-boat”.…”

Synthesis and gene delivery properties of [12]aneN<sub>3</sub>-based nonviral gene vector with near infrared AIE activity

“…诊疗一体化等领域具有重要意义。 本文基于双 [12] 1 引言 将基因递送试剂和生物成像分子进行整合， 实现 治疗和诊断于一体的目标， 成为近年来研究多功能非 病毒基因载体的一个重要方向 [1] 。尽管在转染效率方 面，非病毒基因载体远远落后于病毒基因载体 [2] ，但 是非病毒基因载体具有易于制备，易于修饰和改造， 免疫原性低，生物安全性高等优势，使其成为病毒基 因载体最具潜力的替代品 [3] 。有机小分子荧光团具有 成本低、生物相容性好、灵敏度高以及信噪比(S/N) 高 [4] 等特性而成为一种具有潜力的无创造影剂。因 此， 近年来开发具有强荧光高分辨率的有机小分子荧 光非病毒基因载体引起了科学家们的广泛研究兴趣。 波长在 200 -650 nm 范围内的光学探针通常会 遇到组织自发荧光的强干扰、 高吸收和显著的光子散 射等问题 [5] ，因此，荧光发射在 600 -900 nm 范围 [6] ， 具有深层组织穿透性能并且能够实时进行追踪的近 红外(NIR)发光小分子成为近年来的研究热点 [7,8] 。 其中，聚集诱导发射(AIE)荧光团具有可以通过与 特异性的物种相互作用来激活荧光的特点， 使其最大 限度的减少非特异性干扰并改善空间精确度 [9,10] 。尽 管具有 NIR 发射 [11] 和 AIE 性能 [12,13] 的非病毒基因载 体均有报道，兼具 NIR 发射和 AIE 性能的单个载体 分子 [14,15] [15,16] 。 3 结果与讨论…”

Organic supramolecular aggregates based on water‐soluble cyclodextrins and calixarenes

“…In addition, Wang and coworkers employed a similar supramolecular host–guest strategy to induce mitochondrial aggregation and fusion by using a system composed of CB[7]‐grafted HA and triphenylphosphonium‐ and adamantane‐modified PEG. [ 81 ] This system has potential utility as a therapeutic for mitochondrial fission associated with oxidative stress and may open up new avenues for controlling mitochondrial dynamics.…”