Mitochondrial-targeted penetrating peptide delivery for cancer therapy

ABSTRACT

Introduction: Mitochondria are promising targeting organelles for anticancer strategies; however, mitochondria are difficult for antineoplastic drugs to recognize and bind. Mitochondria-penetrating peptides (MPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into mitochondria. MPPs have combined or delivered a variety of antitumor cargoes and obviously inhibited the tumor growth in vivo and in vitro. MPPs create new opportunities to develop new treatments for cancer.

Areas covered: We review the target sites of mitochondria and the target-penetration mechanism of MPPs, different strategies, and various additional strategies decorated MPPs for tumor cell mitochondria targeting, the decorating mattes including metabolism molecules, RNA, DNA, and protein, which exploited considered as therapeutic combined with MPPs and target in human cancer treatment.

Expert opinion/commentary: Therapeutic selectivity that preferentially targets the mitochondrial abnormalities in cancer cells without toxic impact on normal cells still need to be deepen. Moreover, it needs appropriate study designs for a correct evaluation of the target delivery outcome and the degradation rate of the drug in the cell. Generally, it is optimistic that the advances in mitochondrial targeting drug delivery by MPPs plasticity outlined here will ultimately help to the discovery of new approaches for the prevention and treatment of cancers.

KEYWORDS:

• Cancer
• cell death
• target
• penetration
• drug delivery
• antitumor
• mitochondria-penetrating peptides

Article highlights

• Mitochondria play a key role in apoptosis, programmed cell death, which is essential to the loss of physiological functions in tumor tissues.

• MPPs is one type of CPPs which can target and penetrate mitochondrial membrane. New present studies start to provide a class of new CPPs targeting mitochondria designed and manually synthesized.

• Two major goals in developing therapeutic imaging or agents contrast formulations are accurate targeting selectivity and high delivery efficacy.

• The current strategies for antitumor via targeting mitochondria, two main direction are concluded: repair the tumor cells mitochondrial and revert their function of apoptosis; delivery proapoptosis drugs directly activate mitochondrial apoptosis and promoting cancer cells apoptosis program.

• MPPs’ decorating mattes including metabolism molecules, RNA, DNA, and protein, which may be exploited considered as therapeutic combined with MPPs and target in human cancer treatment.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Funding for this paper was received from the National Nature Science Foundation of China grant (NO. 81501330), and Science Foundation of CTGU grant (KJ2014B066).