Guiding Drugs to Target‐Harboring Organelles: Stretching Drug‐Delivery to a Higher Level of Resolution

Abstract

The ratio between the dose of drug required for optimal efficacy and the dose that causes toxicity is referred to as the therapeutic window. This ratio can be increased by directing the drug to the diseased tissue or pathogenic cell. For drugs targeting fungi and malignant cells, the therapeutic window can be further improved by increasing the resolution of drug delivery to the specific organelle that harbors the drug's target. Organelle targeting is challenging and is, therefore, an under‐exploited strategy. Here we provide an overview of recent advances in control of the subcellular distribution of small molecules with the focus on chemical modifications. Highlighted are recent examples of active and passive organelle‐specific targeting by incorporation of organelle‐directing molecular determinants or by chemical modifications of the pharmacophore. The outstanding potential that lies in the development of organelle‐specific drugs is becoming increasingly apparent.

An intramolecular photoswitch can significantly promote photoactivation of Pt(iv) prodrugs

“…S37 ), which enabled us to monitor its subcellular distribution. Since rhodaplatin 2 is presented as a lipophilic cation, which may easily cross the phospholipid bilayers and accumulate in the mitochondria or endoplasmic reticulum (ER), 21 we treated the cells with rhodaplatin 2 and co-stained the cells with fluorescent trackers of the mitochondria and ER. As shown in Fig.…”

Azide‐Terminated RAFT Polymers for Biological Applications

“…The conjugation on the azide-terminal also provides opportunities to understand the effect of organelle-targeting moieties when conjugated to polymers. Organelle-targeting moieties facilitate the development of imaging and drug delivery (Louzoun-Zada, Jaber, & Fridman, 2019;Xu, Zeng, Jiang, Chang, & Yuan, 2016). For example, different analogs of delocalized lipophilic cations have been utilized to direct therapeutics to the mitochondria, as well as to expand the library of imaging probes for the mitochondria (Johnson, Walsh, & Chen, 1980;Smiley et al, 1991;Zielonka et al, 2017).…”

Light‐Driven Cascade Mitochondria‐to‐Nucleus Photosensitization in Cancer Cell Ablation

“…[17][18][19][20] Therefore, subcellular compartments, including the mitochondria, nucleus, etc., have become targeting sites to enhance anticancer efficiency. [17,[21][22][23] As the central regulator of cell growth and proliferation, nucleus, especially the nucleoli, is considered to be the most aspirational target for most of the therapeutic drugs, especially for malignant tumors. [24][25][26] For instance, nucleus-targeting anticancer drugs, such as doxorubicin, [27] paclitaxel, [28] carboplatin and cisplatin, [29,30] etc., induce cell death by interacting with the DNA helix or its related enzymes.…”