# Engineering Exosome for Ovarian Cancer Targeting Therapy

> **NIH NIH P20** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2021 · $197,510

## Abstract

Despite various therapeutic developments, ovarian cancer is still one of the most lethal diseases in women. In 2018, almost 22,000 women in the US 
were diagnosed with ovarian cancer. Over 14,000 women died from it due to a relative lack of targeted agents leading to systemic toxicity, multidrug 
resistance (MDR) and ultimately to insufficient therapeutic efficacy and metastasis. Thus, ovarian cancer treatment with optimized targeting toward 
the tumor could produce a clinical advantage. Multiple lines of evidence and several clinical trials solidified the idea that extracellular vesicles, called 
“exosomes,” can be a potential cancer-targeting solution due to their small size (40~150 nm), biocompatibility, and therapeutic encapsulation and 
delivery. It is important to note that the surface modification of exosomes could enhance their therapeutic role as a drug delivery system, specifically 
targeting ovarian cancer and improving therapeutic outcomes. Currently, there are two major methods of exosome surface modification to endow 
their active targeting efficacy: 1) genetically engineered mother cells to embed targeting proteins and 2) chemical conjugation of a targeting ligand on 
the exosome. However, both methods require extensive amounts of time and labor to optimize for a feasible clinical application. Thus, alternative 
methods of exosome surface modification must be developed. 
In this proposal, we aim to develop an innovative exosome surface-modification method composed of anchor-spacer-ligand (ASL). Lipophilic 
near-infrared dyes as Anchors will be incorporated into the exosome membrane and produce their nanoconfinement mediated multifold thermal 
energy. It could inhibit tumor growth and trigger drug release, as evidenced by our preliminary data. Spacers will prevent exosome aggregation and 
systemic excretion. As targeting Ligands, we will use antibody candidates derived from the injection of ovarian cancer exosome into the animal 
because they could specifically bind to the exosomes and their mother ovarian cancer cells. Our preliminary data showed that preferential delivery of 
a drug (doxorubicin) to αvβ3 integrin overexpressing ovarian cancer cells and consequent cell killing efficacy by ASL exosomes coated by RGD peptide 
that specifically interaction at αvβ3 integrin. Another preliminary study demonstrated that a newly synthesized co-modulator that simultaneously 
depletes glutathione (MDR contributor) and vascular endothelial growth factor (VEGF: metastasis contributor) inhibits both MDR and metastasis of 
ovarian cancer. 
Therefore, the strategy of combining all of the above advantages into an exosome will make an innovative therapeutic platform to treat 
ovarian cancer, and to our knowledge, it is the first integrated strategy of this type. To achieve this goal, we will prepare a series of anchor-spacerligand 
conjugates and co-modulators and then integrate them to formulate and optimize co-modulator encapsulating ASL exosome...

## Key facts

- **NIH application ID:** 10491434
- **Project number:** 5P20GM103639-09
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Dongin Kim
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,510
- **Award type:** 5
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491434

## Citation

> US National Institutes of Health, RePORTER application 10491434, Engineering Exosome for Ovarian Cancer Targeting Therapy (5P20GM103639-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10491434. Licensed CC0.

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