Table 5 Overview of mitochondria-targeting strategies for cancer treatment

Conventional chemotherapy

A promising strategy that directly acts on mitochondria to produce toxic substances to cells and induces cancer cell death by endogenous chemical energy without the stimulation of external light sources

CT drugs (Betulinic Acid, Resveratrol, Ditercalinium Chloride, Benzo-α-pyrone (coumarin), α-TOS, Organic Arsenicals)

Easy to penetrate mitochondrial membrane and target mitochondria due to high lipid solubility; high effectiveness of tumor treatment

[556, 604, 605]

Nanoplatform loaded with CT/RT drugs

CT/RT drugs are modified by mitochondria-targeting units or designed as nanoplatforms for cancer treatment

CT/RT drugs (Lonidamine, Paclitaxel, Doxorubicin, Cisplatin); mitochondria-targeting units

High effectiveness of tumor treatment

[557, 587, 606]

CDT

A burgeoning therapy through undergoing a fenton reaction or a fenton-like reaction, which reacts with excessive intracellular hydrogen peroxide (H₂O₂) in tumor tissues to generate hydroxyl radicals (·OH)

CT drugs; mitochondria-targeting units

Low invasiveness; consumption of endogenous H₂O₂ without external energy; little normal tissue toxicity

[576, 577]

PTT

Killing cancer cells with thermal damage (conversion of light energy into heat) utilizing an external light source (usually near-infrared (NIR) light) and photothermal agent as heat-generating source; PTT has strong absorption characteristics for NIR

Photothermal materials, external light source; mitochondria-targeting unit

Deep penetration and minimal damage to surrounding healthy tissue; noninvasiveness;

Minimal side effects; temporal and spatial selectivity

[567, 607, 608]

PDT

A locally targeted therapy utilizing a photosensitizer (PS), light, and oxygen to selectively kill tumors

PS, light, oxygen, serval lipophilic, and cationic groups

Accurate controllability; minimal drug resistance

[562, 570, 572]

RT-RDT

Stimulating PS to produce ¹O₂ to kill tumors under ionizing radiation

PS, ¹O₂, and mitochondria-targeting unit

Reach deeper tissues; low dosage possessing effective therapeutic effect

[609, 610]

SDT

To kill cancer cells by stimulating exogenous (ultrasound) to activate SDT agents for producing ROS, cavitation, air bubbles, and hyperthermia

Ultrasound, SDT agents, ROS, cavitation, air bubbles, and hyperthermia

Depth of tumor tissues can be realized by ultrasound;

Achievement of noninvasive treatment; high precision of target lesion zones

[611]

Gene therapy

Replacement of defective genes by delivering wild-type ones into the host cell, or silencing a dominant mutant allele that is pathogenic to address mitochondrial diseases,

Therapeutic cargoes; delivery system

Precision treatment

[612,608,614]

Gas therapy

Using gaseous molecules to combat cancer

Gaseous molecules such as nitric oxide, CO, hydrogen sulfide, and hydrogen; mitochondria-targeting unit

Noninvasive in situ treatment with no depth limit

[615, 616]

Combination therapy

Combination of CT and PTT, CT and CDT, PDT and PTT, PDT and CDT; PDT and CT; PDT and Immunotherapy

/

Achieve synergistic effect of anticancer; minimize multidrug resistance; reduced pain in patients

[579, 617,613,614,620]