Organometallic Rhenium Complexes Divert Doxorubicin to the Mitochondria

Abstract

Doxorubicin, a well-established chemotherapeutic agent, is known to accumulate in the cell nucleus. By using ICP-MS, we show that the conjugation of two small organometallic rhenium complexes to this structural motif results in a significant redirection of the conjugates from the nucleus to the mitochondria. Despite this relocation, the two bioconjugates display excellent toxicity toward HeLa cells. In addition, we carried out a preliminarily investigation of aspects of cytotoxicity and present evidence that the conjugates disrupt the mitochondrial membrane potential, are strong inhibitors of human Topoisomerase II, and induce apoptosis. Such derivatives may enhance the therapeutic index of the aggressive parent drug and overcome drug resistance by influencing nuclear and mitochondrial homeostasis.

Mitochondria‐Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer

“…The mitochondria‐targeting effect of MMCNs is additionally corroborated by inductively coupled plasma atomic emission spectrometer (ICP‐AES), since the presence of Fe elements in MMCNs allows sensitive quantification of the metal content in the cellular compartments after subtracting the baseline Fe levels in different organelles of untreated cells . Remarkably, the Fe quantification evidences a significant accumulation of MMCNs in the mitochondria (Table S3, Supporting Information).…”

A Rhenium Isonitrile Complex Induces Unfolded Protein Response‐Mediated Apoptosis in Cancer Cells

“…[12][13][14][15] Certain members of this class of compounds exhibit potent cytotoxic activity,w hich can be leveragedf or their use as anticancer agents. [16][17][18][19][20][21][22][23] Here, we describe our investigation of an ew rhenium(I) tricarbonyl complexb earing ac helating polypyridyl liganda nd an axial isonitrile ligand as ap otent anticancer agent.O ur efforts to understand the mechanismo f actiono ft his tricarbonyl rhenium isonitrile polypyridyl (TRIP) complex ( Figure 1) have revealed that it is an effective ER stress-inducing agent with significant antiproliferativeactivity. TRIP was synthesized by treating the previously reported complex [Re(CO) 3 (dmphen)OTf] with excess para-tolyl isonitrile in tetrahydrofuran.…”

Organic Mitoprobes based on Fluorogens with Aggregation‐Induced Emission

“…[21] A variety of fluorescent agents, including quantum dots (QDs), [22] organometallic compounds, [23] fluorescent proteins (FPs), [24] organic dyes, [25] and so on, have been developed and used in mitochondrial dynamism tracking and monitoring. It utilizes fluorescent agents to label mitochondria with real-time operation, non-invasive testing and cost-effective performance.…”