Page 32 - ITPS-7-2

INNOSC Theranostics and
Pharmacological Sciences Mitochondria and aging

inflammatory markers such as tumor necrosis factor α, mitochondria as well as overcome drug resistance and
interleukin 6 (IL-6), regulated upon activation, normal reduce the unwanted effects of the delivered drugs. Mito-
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T cells expressed and secreted (RANTES), and IL-1 lonidamine and cisplatin are two typical instances of
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receptor antagonist protein (IL-1ra). However, new mitochondria-targeted anticancer medications that promote
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research indicates that not every type of cell-free mtDNA programmed cell death and thereby prevent cancer cell survival,
is pro-inflammatory, nor does it seem to be sufficient progression, and metastasis. Interestingly, mitoNANOs
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to consistently cause inflammation. Consequently, loaded together with lonidamine showed 10-fold higher
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this belief may be the result of a misunderstanding of antitumor properties in comparison to pure lonidamine.
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correlational clinical investigations, and it should be tested Furthermore, research indicates that mitochondria-targeted
and re-evaluated in relevant biological systems. NPs have antiproliferative and cytotoxic impacts in tumor
cells but not in healthy cells. Moreover, mitoNANO-based
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9. Mitochondria-targeted drug delivery therapies can accelerate mitochondrial blockades in cancer
approaches in age-related diseases cells through multiple ways, including respiratory inhibition,
Mitochondrial-targeted therapeutics are recognized as modulation of the mitochondrial permeability transition
a revolutionary tool for diagnosing, preventing, and pore, inhibition of the ETC, inhibition of anti-apoptotic
treating a wide range of age-related human diseases, protein family members, suppression of phenotypes linked to
including cardiovascular disease, metabolic disorders, mutated DNA, and the promotion of mitochondrial-regulated
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cancer, and neurodegenerative diseases. Nonetheless, the cancer cell death. In general, intracellular uptake is the first
mitochondria are made up of at least six compartments: step for NPs to transport the drugs to the mitochondria. To
the outer membrane, inner border membrane, IMS, complete this process, the cell membrane’s negatively charged
cristal membranes, intracristal space, and matrix. phospholipids must adhere to the positively charged, minute
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Hence, effective mitochondria-targeted drug delivery is NPs, which leads to drug endocytosis and the formation of
challenging owing to the mitochondrial double-membrane endolysosomes. Then, the endolysosomal membrane rupture
and its complex structure, as well as the highly negative occurs inside the cytoplasms, which results in the release of its
potential nature of the membrane. Therapeutic and tiny contents, and the mitochondria to be targeted intracellularly.
compounds, on the other hand, may diffuse through There are various NP-based drug delivery methods
the outer membrane through passive diffusion and used to treat mitochondrial disorders that aid in protecting
phospholipid cardiolipin. It is noteworthy to mention drug payloads, including hydrophobic and hydrophilic
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that the pore in the outer membrane is wider, and hence, compounds, from their elimination and degradation.
therapeutic molecules can easily traverse through this NPs are classified into different groups according to
pore. The limited, highly folded inner mitochondrial their chemical and physical characteristics, surface area,
membrane, on the other hand, has narrower transition slits shapes, or sizes, including liposomes, liposome-like
that separate the mitochondrial matrix and IMS, making vesicles (DQAsomes), MITO-porters, micelles, polymeric
it difficult for many therapeutic compounds to cross the NPs, dendrimers, metal NPs such as gold NPs (AuNPs),
mitochondrial matrix. Nanotechnology has brought new quantum dots, or nanoscale semiconductor crystals, and
hope over the years by bringing innovative compounds, each of them possesses specific features. In addition,
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such as nanoparticles (NPs), that can be employed for the they can be accumulated in tumor cells utilizing either
clinical diagnosis and prognosis of a variety of illnesses, active or passive targeting techniques. The latter technique
including numerous cancer kinds. 257,258 Furthermore, uses the enhanced permeability and retention phenomena
because of their deep tissue penetration capabilities, and particular features of solid tumors, such as leaky
NPs not only increase drug half-life and increase drug vasculature and disrupted lymphatic drainage, which
accumulation in tumor tissues, 257-259 but they also provide a results in NP extravasation throughout the leaky blood
platform for weakly soluble medicines to be encapsulated arteries. On the other hand, active targeting is based on
and delivered more efficiently into circulation. In the ligand-receptor interaction system, which means that
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addition, they can be rationally engineered to target certain ligands attached to NPs can recognize molecules that are
intracellular organelles such as mitochondria, ER, selectively overexpressed in tumor cells. The passive target
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Golgi apparatus, and lysosomes. Recently, multiple technique for synthesizing mitoNANO provides some
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organic and inorganic NPs combined with conventional merits, such as simplicity and cost-effective synthetic
chemotherapeutic medicines to produce biocompatible, procedure. However, the aggregation behavior of passively
multifunctional mitochondria-targeted nanoplatforms. targeted NPs provides a reason for concern because it can
Nevertheless, mitochondria-targeted NPs (mitoNANO) result in their rapid clearance from the biological system.
evolved to enhance the therapeutic targeting of The active targeting of the mitoNANO approach requires

Volume 7 Issue 2 (2024) 10 doi: 10.36922/itps.1726