Targeting Mitochondria

Mitochondria are vital organelles to eukaryotic cells and damage to mitochondria will cause irreversible cell death or apoptosis. Selective delivery of therapeutic agents to cancer cell mitochondria presents a significant influence on the programmed cell death in cancer therapy. As an industry leader in providing custom service to help clients discover and develop novel therapeutic approaches , Creative Biolabs provides a wide range of targeted delivery services targeting mitochondria. Here, modules targeting cell surface and mitochondria could be conjugated together onto different module delivery systems for the delivery of therapeutic agents into a specific intracellular site.

Mitochondria

The primary role of mitochondria in eukaryotes is to provide adenosine triphosphate (ATP) to the cell by the process of oxidative phosphorylation. Besides playing a key role in apoptosis, mitochondria also modulate the intracellular calcium concentration and carry out oxidative phosphorylations via the mitochondrial respiratory chain. Consequently, the malfunctioning of mitochondria is found in several adult-onset diseases such as obesity, infertility, blindness, deafness, cardiomyopathy, diabetes, Parkinson’s, migraine, kidney and liver diseases, and stroke. Treatment strategies may include the delivery of antioxidants to protect mitochondria from oxidative stress or pro-apoptotic drugs, which could trigger apoptosis in tumor cells. What’s more, proteins and peptides may be delivered for the treatment of a wide range of mitochondrial disorders.

Mitochondrial Targeting Strategy

• The lipophilic triphenylphosphonium (TPP) cation is a classic mitochondrial anchor that has been demonstrated to effectively deliver payloads into mitochondria via electrostatic interactions. For instance, the TPP cation specifically delivers the pro-apoptotic peptide to its particular subcellular mitochondria after internalized by cancer cells. Then the pro-apoptotic peptide accumulates in mitochondria and causes its serious damage.

Fig.1 TPP-based mitochondria-targeted anticancer drugs mainly target tumor cells with high membrane potential and deliver the drug to the tumor cell mitochondria to kill or treat them.¹

• _D(KLAKLAK)₂ (KLA) peptide specifically disrupts the mitochondrial membrane and initiates apoptotic cell death, while remains relatively non-toxic outside of cells. A study reported a polymeric delivery system modified with the G3-C12 peptide (targeting galectin-3) and KLA for sequential dual targeting from cell membrane to intracellular mitochondria. In that case, G3-C12-copolymer-KLA peptide disrupted the mitochondrial membrane, increased the generation of reactive oxygen species (ROS) and induced cytochrome c release, which ultimately resulted in enhanced cytotoxicity.

Fig.2 Schematic of (A) KLA-5-FU/PTX Lps and (B) the mechanism by which they target tumor cells and mitochondria to induce apoptosis.²

• Mitochondria are subcellular compartment that can be specifically targeted by modified cell penetrating peptides (CPPs). Mitochondria-specific CPPs may thus provide a solution for anti-apoptotic or antioxidant therapies for many common diseases. One strategy to target mitochondria is to incorporate a mitochondrial signal sequence, such as mitochondrial malate dehydrogenase (mMDH) signal sequence into a CPP fusion protein. Mitochondria penetrating peptides (MPP) were designed and its efficiency can be optimized by altering lipophilicity and charge.

What Can We Do for you?

Equipped with our well-established module delivery systems, we provide either individual targeting modules or different kinds of module-payload/carrier conjugates targeting mitochondria. A wide spectrum of corresponding products are also available. To enhance the therapeutic effect, many therapeutic agents need to be localized in particular subcellular organelles. Creative Biolabs has gained abundant experience in the field of targeted delivery. Our professional scientist team enable us to provide high-quality mitochondria-targeting delivery services for our worldwide customers. If you are interested in our services, please don’t hesitate to contact us for more information.

References

1. Cheng, Xiaoxia, et al. "Application Prospects of Triphenylphosphine-Based Mitochondria-Targeted Cancer Therapy." Cancers 15.3 (2023): 666.
2. Chen, Tianyu, et al. "Co-delivery of 5-fluorouracil and paclitaxel in mitochondria-targeted KLA-modified liposomes to improve triple-negative breast cancer treatment." Pharmaceuticals 15.7 (2022): 881.

Our services are For Research Use Only. We do not provide services to individuals.