Abstract

Lung cancer remains the leading cause of cancer-related deaths. Despite advancements in treatment, there are still many shortcomings. Exosomes derived from NK cells naturally carry potent cytotoxic proteins that can induce apoptosis in cancer cells. However, their therapeutic effectiveness is limited by poor targeting specificity.

To address this, we functionalize NK92-derived exosomes with DNA origami scaffolds displaying the S2.2 MUC1 aptamer. Our DNA origami design is folded into a planar structure, with one side conjugated to an aptamer that binds to NK-92 exosomes, while the aptamers on the opposite side of the plane can bind to A549 target cells. This modification will enhance binding and uptake by A549 lung cancer cells, which overexpress MUC1, thereby improving the specificity and efficacy of the exosome-mediated cytotoxicity. We hypothesize that this aptamer-driven targeting will increase exosome delivery to A549 cells.

Short Introduction

Motivation

According to the World Health Organization material, lung cancer has the highest cancer mortality rate worldwide. Then traditional chemotherapy prevents tumor proliferation and metastasis by inhibiting rapid cell division, but due to its lack of selectivity, it often damages normal cells at the same time, leading to serious side effects. However targeted drug therapy can provide short-term inhibitory effects, it is still limited by genotype differences, drug resistance and recurrence. So we use DNA origami. The structure, used as a high-precision nanocarrier combined with NK92-derived exosomes, can improve the targeting of lung cancer cells and then use the ability of exosomes to kill cancer cells.

Design

To construct a functionalized DNA origami nanostructure, we designed a triangular DNA plane incorporating three distinct functional DNA fragments. The M13mp18 (ssDNA, p7249) was used as the scaffold, and approximately 200 staple strands were designed using caDNAno to fold the scaffold into a planer equilateral triangle.

Future

Due to time constraints, subsequent experiments are still ongoing and have not been completed. Please see the following three points.

  1. Purify exosomes from NK92 cell culture medium.
  2. Establish a stable binding system between DNA origami and exosomes.
  3. Evaluate the specific binding ability and cytotoxicity of the combined complex to A549 lung cancer cells.
Ultimately, this study hopes to establish a nanoscale delivery system with both targeted and immune regulation potential as the basis for future immune-related applications.