Structural and mechanistic insights into α2β1 and α5β1 integrin targeting by bioengineered extracellular vesicles originating from lung cancer cells

Sep 23, 2026

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Integrins are transmembrane receptors governing signaling linked to tumor progression, metastasis, and intercellular communication. The study compares the structural and biophysical interaction of PTHTRWA-functionalized extracellular vesicles with α2β1 and α5β1 integrins to define molecular determinants of selective recognition. Surface plasmon resonance characterizes multivalent binding under physiological conditions, while molecular dynamics reveals residue-level ligand–receptor patterns and conformational preferences. PTHTRWA binding correlates with local conformational rearrangements compatible with an open-like binding geometry, supporting targeted delivery and diagnostic potential.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Targeted therapy and precision treatment for lung cancer

Extracellular vesicles for targeted drug delivery

Methods and rationale

PTHTRWA as a navigation ligand

Prior evidence and functionalization strategy

Integrin targeting analysis

Structural and biophysical comparison of EV–integrin interactions

Surface plasmon resonance and molecular dynamics approach

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Structural and mechanistic insights into α 2β1 and α 5β1 integrin targeting by bioengineered extracellular vesicles originating from lung cancer cells Anna M. Nowicka1􀀍, Teresa Żołek2,4, Agata Kowalczyk1,4 & Ireneusz P. Grudzinski3􀀍 Integrins are transmembrane receptors that mediate bidirectional signaling across the plasma membrane and play a crucial role in tumor progression, metastasis, and cellular communication. In this study, we performed a comparative structural and biophysical analysis of the PTHTRWA-functionalized extracellular vesicles (PTHTRWA-EVs) interacting with α2β1 and α5β1 integrins to investigate the molecular determinants underlying selective recognition. Surface plasmon resonance experiments were used to characterize multivalent bioengineered EVs---integrin binding under physiological conditions, while molecular dynamics simulations provided residue-level insight into local ligandreceptor interaction patterns and conformational preferences. These results indicate that PTHTRWA binding is associated with local conformational rearrangements consistent with stabilization of an open-like binding geometry at the integrin interface. Together, these complementary approaches highlight the potential of PTHTRWA-functionalized EVs as a platform for targeted drug delivery and cancer diagnostics. Keywords Integrins α2β 1 and α5β 1, Lung cancer–derived extracellular vesicles, Molecular dynamics simulations, Ligand-induced conformational changes in integrins, Binding affinity of the PTHTRWA-EVsintegrin complex Over the past two decades, lung cancer has consistently ranked among the three most frequently diagnosed malignancies worldwide1,2. Unfortunately, the course of this disease is highly insidious - it develops without symptoms for a long time, meaning it is often diagnosed too late to be treated effectively3. These factors highlight the urgent need for new, more precise, and less toxic therapeutic strategies. Undoubtedly, the key element of effective lung cancer therapy is individualized treatment4. The choice of the best treatment strategy should take into account the specific characteristics of the tumor (subtype, stage, and location), as well as the patient’s health, comorbidities, and preferences5. In recent years, there has been a particular intensification of research into targeted therapy6–10. It is a modern method of cancer treatment that involves identifying and attacking specific characteristics of cancer cells. It works by inhibiting specific molecular pathways, which allows for the precise targeting of only those cells that are responsible for the development of cancer11. This therapy is often referred to as personalized medicine it considers the individual characteristics of each patient’s cancer. Thanks to research into the mechanisms of cancer development, targeted therapy has become a key element of modern cancer treatment. Research in this area includes both the search for new forms of drug administration and improvements in delivering the drug only to cancer cells. In the context of precise drug delivery systems targeting cancer cells, extracellular vesicles (EVs) have attracted particular attention in recent years. The main focus of research is on the use of extracellular vesicles as natural, biodegradable nanovesicles for transporting drugs directly to cancer cells12, 13. Their natural ability to communicate between cells and the fact that EVs are secreted by most eukaryotic cells, and are therefore unique to 1Faculty of Chemistry, University of Warsaw, 1 Pasteura St, Warsaw PL-02-093, Poland. 2Department of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha St, Warsaw PL-02-097, Poland. 3Department of Toxicology and Food Science, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha St, Warsaw PL-02-097, Poland. 4Teresa Żołek and Agata Kowalczyk contributed eq

FAQs

What are the main integrins and EVs studied in this work?

The work focuses on integrins α2β1 and α5β1 and on extracellular vesicles originating from lung cancer cells that are functionalized with the PTHTRWA heptapeptide.

How are PTHTRWA-functionalized EV–integrin interactions investigated?

Surface plasmon resonance is used to characterize multivalent binding under physiological conditions, and molecular dynamics simulations provide residue-level views of ligand–receptor interaction patterns and conformational preferences.

What does the study conclude about the mechanism of PTHTRWA binding?

PTHTRWA binding is associated with local conformational rearrangements consistent with stabilization of an open-like binding geometry at the integrin interface.

Sep 23, 2026

Upload by Jacob