Table 1.

Mitochondria specific drug delivery and targeting strategies of nanoparticles used in cancer treatment.

Targeting Moieties	Nano-carriers and conjugates	Targeting strategies and molecular action	Outcome	Ref
CD437	–	Inhibits POLA1; affects Mptpc; releases cytochrome C	Apoptosis	(Han et al., 2016)
Arsenic trioxide	–	Affects mPTPC; inhibits BCL2 and BCLXL	Apoptosis	(Cervantes-Madrid et al., 2015)
Cyclosporine A (CsA)	PLGA (Poly lactic co-glycolic acid)	Affects mPTPC	Apoptosis	(Zhang et al., 2019)
Lonidamine (LND)	–	Inhibits hexokinase 2 (HK2)	Apoptosis	(Wang et al., 2014)
Etoposide (VP-16)	–	Topoisomerase II inhibitor	Apoptosis	(Custódio et al., 2001)
MKT-007 (Rhodacyanin)	–	Prevents ATP synthesis in tumour cells;	Tumor cell death; nephrotoxicity	(Starenki and Park, 2015)
Elesclomol	–	Inhibits ETC; blocks ATP synthesis, induces ROS	Apotosis	(Nagai et al., 2012)
Metformin/Phenormin	–	AMPK activator; blocks ATP synthesis	Apoptosis	(Scotland et al., 2013)
Oligomycin A	–	Inhibits ATPase; affects mPTPC; induces ROS	Apoptosis	(Mandujano-Tinoco et al., 2013)
CB 839	–	Inhibits glutaminase	Apoptosis	(Meric-Bernstam et al., 2019)
Tamoxifen	–	Inhibits topoisomerase;	Apoptosis	(Jafari and Fatemi, 2020)
Nucleic acid, peptides, CsA	Triphenylphosphonium (TPP) - mitochondriotropic	Drug accumulation	Cytotoxicity	(Trnka et al., 2015, Larosche et al., 2007)
Porphyrins	TPP	Drug accumulation	Photo-cytotoxicity	(Yang et al., 2019)
TEMPOL	TPP	Drug accumulation	Apoptosis	(Trnka et al., 2009)
Topotecan, DOX, Cisplatin	TPP- antibiotic peptide (KLAKLAK)2- Mesoporous silica nanoparticles (MSN); MSN-amino silane and EDC (1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide and N-hydroxysuccinimide)-TPP	Lowered ATP production; decreased mitochondrial membrane potential , Drug accumulation, facilitates endocytosis	Cytotoxicity	(Zhang et al., 2012, Shi et al., 2018, Choi et al., 2015)
Bombesin receptor (BnR) antagonists	BnR peptides	Targeted delivery	Cytoxicity	(Moreno et al., 2016)
Mastoparan	Liposomes were altered with fusogenic and transferring peptide (Chol-GALA)	Affects MPT	Cell death	(Yamada et al., 2015)
DOX	Hypericin-Graphene oxide	Increased phototherapy and chemotherapy	Cell death	(Han et al., 2018)
Methyl coumarin	TPP	Inhibited proliferation, induced ROS generation, reduced mitochondrial membrane potential, promotes Ca2+ accumulation,	Apoptosis	(Wang and Xu, 2017)
Celastrol	PEGylated polyaminoacid-capped CST-loaded MSN	Controlled in vitro drug release;	cytotoxicity Apoptosis	(Choi et al., 2018)
Paclitaxel	Liposomes-rhodamine- 123-conjugated polymer; Dequalinium (DQA) DQA-PEG(5000)-DSPE –mitochondriotropic molecule. Steoryltriphenylphosphonium (STPP)-based liposomes	Affects mPTPC; Increases drug accumulation; DQAsomes; inhibiting the mtDNA synthesis in cancer cells; Increases intracellular Ca2+ homeostasis and cytochrome c release	Tumor cell death.	(Biswas et al., 2012, Solomon et al., 2013)
Gamitrinibs	TPP	Specifically antagonize the ATPase pocket on Hsp90	Tumor cell death.	(Fiesel et al., 2017)
Green fluorescent protein (GFP) as a model	MITO-Porter	Facilitates macropinocytosis and delivers cargo (drugs) to mitochondrial matrices.	Targeted drug delivery to cancer cell.	(Kawamura et al., 2020)
Mesochlorin e6	N-(2-hydroxylpropyl) methacrylamide (HPMA)-TPP	Enhanced effect of specific combined targeting of tumor cells and mitochondria	Apoptosis	(Cuchelkar et al., 2008)
Hypocrellin A	water-soluble amorphous silica nanocage (HANC)	Small size ensures specific targeting and delivery	Apoptosis	(Zangabad et al., 2017)
Proteins	Intracellular Delivery of Proteins with Cell-Penetrating Peptides for Therapeutic Uses in Human Disease	Uptake of exogenously delivered proteins	Apotosis	(Dinca et al., 2006)
Dye-labeled to track uptake	Mitochondria penetrating peptides (MPP)	Imparts positive charge and lipophilic potential	Maximizes drug delivery	(Alta et al., 2017)