Mitochondria-Targeted Nanomedicine for Enhanced Efficacy of Cancer Therapy.

Yan Gao,Jialiang Li,Haibei Tong,Jiachen Li,Bing Xia,Jisen Shi,Di Huang

doi:10.3389/fbioe.2021.720508

Yan Gao, Jialiang Li + Show 5 more

Open Access

https://doi.org/10.3389/fbioe.2021.720508

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Abstract

Nanomedicines have been designed and developed to deliver anticancer drugs or exert anticancer therapy more selectively to tumor sites. Recent investigations have gone beyond delivering drugs to tumor tissues or cells, but to intracellular compartments for amplifying therapy efficacy. Mitochondria are attractive targets for cancer treatment due to their important functions for cells and close relationships to tumor occurrence and metastasis. Accordingly, multifunctional nanoplatforms have been constructed for cancer therapy with the modification of a variety of mitochondriotropic ligands, to trigger the mitochondria-mediated apoptosis of tumor cells. On this basis, various cancer therapeutic modalities based on mitochondria-targeted nanomedicines are developed by strategies of damaging mitochondria DNA (mtDNA), increasing reactive oxygen species (ROS), disturbing respiratory chain and redox balance. Herein, in this review, we highlight mitochondria-targeted cancer therapies enabled by nanoplatforms including chemotherapy, photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), radiodynamic therapy (RDT) and combined immunotherapy, and discussed the ongoing challenges.

Highlights

Cancer still presents a major threat to human health, causing over eight million related death every year and enormous economic loss (Ferlay et al, 2015)
Co-localization experiment with organelle trackers showed that Mito-coumarin iron oxide (CIO) and CIO were mainly localized within mitochondria and endoplasmic reticulum respectively. These results indicated that TPP as a vector to direct Mito-CIO to mitochondria resulted in hyperthermia in mitochondria, which is mainly responsible for substantial improvement of the cytotoxicity on cancer cell
Various mitochondria-targeted nanomedicines have been developed for chemotherapy, photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), radiodynamic therapy (RDT) and combined immunotherapy to improve anticancer therapy efficacy

Summary

INTRODUCTION

Cancer still presents a major threat to human health, causing over eight million related death every year and enormous economic loss (Ferlay et al, 2015). In addition to the passive accumulation, nanoparticles with active targeting performance are employed to deliver drugs, by modifying specific ligands with high affinity to cancer cells (e.g. polypeptides (Fang et al, 2020; Kang et al, 2020), proteins, antibodies (Chen et al, 2012; Pan et al, 2021), folic acids (Mitra et al, 2018) and aptamers (Tang et al, 2020; Tian et al, 2021)) On this basis, the unique advantages of nanocarriers have been widely demonstrated including long-term sustained (Xia et al, 2019) and controlled release (Xia et al, 2014) and the integration with more diagnostic or therapeutic modality such as multimodal imaging (Gao et al, 2017; Xia et al, 2017; Liu et al, 2019), photodynamic therapy (PDT) (Lucky et al, 2015; Wen et al, 2020), photothermal therapy (PTT) (Xia et al, 2016; Yang et al, 2017) and immunotherapy (Meraz et al, 2012; Secret et al, 2013). The guanidine group of arginine in SS peptide provides cations while the TABLE 1 | A summarization of mitochondria-targeted cancer therapies in which nanoparticles used, with their targeting ligands and tumor cells are used to demonstrate their efficacies

Test objects

HeLa cells and tumor model

PDT Combined with PTT for Synergistic Effects

Findings

CONCLUSION AND FUTURE PROSPECT