# Tumor-targeted multifunctional extracellular vesicles as drug carriers for lung cancer therapy

## TL;DR

Researchers developed tumor-targeted extracellular vesicles to deliver chemotherapy drugs more effectively and with less toxicity in lung cancer treatment.

## Contribution

The novel approach combines nanotechnology and extracellular vesicles with a pH-sensitive drug delivery system for targeted lung cancer therapy.

## Key findings

- Tumor-targeted EVs showed greater drug release at acidic tumor pH (5.5) compared to normal pH (7.2).
- The EVs significantly reduced viability of TfR high A549 lung cancer cells compared to non-targeted EVs.
- Tumor-targeted EVs induced higher apoptosis and DNA damage in cancer cells while sparing normal lung cells.

## Abstract

Aim: Chemotherapy continues to be the frontline treatment for lung cancer patients. However, treatment-related toxicity and off-target effects limit the use of chemotherapy. Therefore, improvements in delivering chemotherapeutics with reduced toxicity to normal tissues are needed. In the present study, we combined nanotechnology with extracellular vesicle (EV) technology to produce tumor-targeted multifunctional EVs (tt-Mfn-EVs) as drug carriers for cancer therapy.

Methods: The tt-Mfn-EVs were formulated by exogenously loading EVs with gold nanoparticles conjugated to cisplatin (CDDP) via pH-sensitive coordination ester linkage. Attached to the outer surface of drug-loaded EVs is the transferrin ligand for targeting transferrin receptor (TfR) overexpressing lung cancer cells.

Results: The tt-Mfn-EVs were 138.2 nm in size and exhibited greater drug release kinetics at pH 5.5 compared to pH 7.2. They significantly reduced cell viability of A549 (TfR high) lung cancer cells compared to HCC827 (TfR low) cells and non-targeted EVs. Tt-Mfn-EVs also induced higher levels of apoptosis and DNA damage in A549 and HCC827 cells compared to control groups. Finally, tt-Mfn-EV-mediated cytotoxicity was minimal in normal human lung fibroblast (MRC-9) and human embryonic kidney 293 (HEK293) cells compared to free CDDP.

Conclusion: Our study showed that tt-Mfn-EVs exerted selective and enhanced tumor-targeted cell killing in vitro, providing an opportunity for developing EV-based drug carriers for cancer therapy.