# Microenvironment‐Guided Evolution of ssDNA‐SWCNT Probes for Selective Recognition of Aggressive Prostate Cancer Phenotypes

## TL;DR

Researchers developed DNA-based nanosensors that can detect aggressive prostate cancer cells by sensing their unique environment, improving cancer diagnostics and treatment.

## Contribution

A microenvironment-guided strategy to evolve ssDNA-SWCNT probes for selective recognition of aggressive prostate cancer phenotypes.

## Key findings

- Two ssDNA-SWCNT probes (PC3D2 and PC2D2) were developed to selectively bind aggressive prostate cancer cells.
- The probes emit NIR-II fluorescence, enabling non-invasive detection of cancer phenotypes in 3D tumor models.
- The probes enabled selective drug delivery to prostate cancer spheroids, improving therapeutic efficacy.

## Abstract

Despite advances in prostate cancer detection, distinguishing indolent from aggressive phenotypes remains challenging. We report a microenvironment‐guided strategy for evolving phenotype‐specific molecular probes using single‐stranded DNA‐functionalized single‐walled carbon nanotubes (ssDNA‐SWCNTs). Our approach employs 3D tumor models that recapitulate complex cancer microenvironments, enabling identification of ssDNA sequences with differential binding properties. We developed two distinct probes for prostate cancer cells: PC3D2, which preferentially binds hypoxia‐adapted stem‐like cells associated with treatment resistance, and PC2D2, which shows enhanced binding to mesenchymal‐like cells. These probes exhibit characteristic second near‐infrared (NIR‐II, 1000‐1700 nm) fluorescence, enabling non‐invasive detection of aggressive phenotypes in heterogeneous tumors using NIR‐II optical imaging. We demonstrate their utility for selective drug delivery to prostate cancer spheroids, resulting in enhanced therapeutic efficacy. This platform represents a significant advancement in precision diagnostics and theranostics, potentially transforming prostate cancer management through phenotype‐specific targeting. The methodology offers a generalizable approach for developing nanoprobes that recognize clinically relevant cancer phenotypes based on their unique microenvironmental signatures rather than individual biomarkers.

Random ssDNA–SWCNT(single strand DNA‐single walled carbon nanotube) library is functionally screened and evolved using high‐throughput 3D prostate tumor spheroids via iterative positive and negative selection, enabling the identification of NIR‐II fluorescent ssDNA‐SWCNT nanoprobe specific for prostate cancer.