Mitochondria-Targeted Nanomedicine for Enhanced Efficacy of Cancer Therapy

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.

Multifunctional Mitochondria-Targeting Nanosystems for Enhanced Anticancer Efficacy

“…(4) Mitochondria are in charge of energy metabolism and tumor cell proliferation: Recent studies have illustrated that tumor cells could promote the generation of glutamine by oxidizing glucose-derived pyruvate through the pyruvate dehydrogenase (PDH)-dependent pathway in mitochondria, which is crucial for tumor growth ( Woolbright et al, 2019 ; Khan et al, 2020 ; Nie et al, 2020 ). Therefore, precise delivery of anticancer agents to mitochondria can be a novel strategy for enhanced cancer treatment ( Weinberg and Chandel, 2015 ; Vasan et al, 2020 ; Guo et al, 2021 ; Gao et al, 2021 ; Zhu et al, 2021 ). Nowadays, various therapeutic strategies, such as chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), chemodynamic therapy (CDT), and combined immunotherapy based on mitochondria targeting nanoplatforms, have been applied to achieve better therapy efficacy ( Figure 1 , from Gao et al, 2021 ).…”

“…Therefore, precise delivery of anticancer agents to mitochondria can be a novel strategy for enhanced cancer treatment ( Weinberg and Chandel, 2015 ; Vasan et al, 2020 ; Guo et al, 2021 ; Gao et al, 2021 ; Zhu et al, 2021 ). Nowadays, various therapeutic strategies, such as chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), chemodynamic therapy (CDT), and combined immunotherapy based on mitochondria targeting nanoplatforms, have been applied to achieve better therapy efficacy ( Figure 1 , from Gao et al, 2021 ). However, mitochondria have a four-layer structure with a high negative potential (−160 to −180 mV), which thereby prevents many molecules from reaching the mitochondria ( Frey and Mannella, 2000 ; Tait and Green, 2010 ; Battogtokh et al, 2018 ; Gao et al, 2021 ).…”

“…Nowadays, various therapeutic strategies, such as chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), chemodynamic therapy (CDT), and combined immunotherapy based on mitochondria targeting nanoplatforms, have been applied to achieve better therapy efficacy ( Figure 1 , from Gao et al, 2021 ). However, mitochondria have a four-layer structure with a high negative potential (−160 to −180 mV), which thereby prevents many molecules from reaching the mitochondria ( Frey and Mannella, 2000 ; Tait and Green, 2010 ; Battogtokh et al, 2018 ; Gao et al, 2021 ). Luckily, the development of nanotechnology has provided the great potential to overcome the membrane barriers.…”

“… Mitochondria-targeted therapeutic strategies based on nanosystems containing chemotherapy, PDT, PTT, SDT, CDT, RDT, and combined immunotherapy ( Gao et al, 2021 ). …”

Mitochondria-Targeted Self-Assembly of Peptide-Based Nanomaterials

“…Increasing evidence has revealed the relevance between the energetic production, metabolic biosynthesis, and singling pathways of mitochondria with the carcinogenesis (Weinberg and Chandel, 2015). Therefore, the mitochondrion has been recognized as a promising target to improve cancer therapeutics (Fulda et al, 2010;Vasan et al, 2020;Gao et al, 2021).…”