Selective Photo-Assisted Eradication of Triple-Negative Breast Cancer Cells through Aptamer Decoration of Doped Conjugated Polymer Nanoparticles.

Luis Exequiel Ibarra,Laura Cerchia,Simona Camorani,Lisa Agnello,Rodrigo Emiliano Palacios,Luciano Pirone,Monica Fedele,Emilia Pedone,Carlos Alberto Chesta

doi:10.3390/pharmaceutics14030626

Abstract

Photodynamic therapy (PDT) may be an excellent alternative in the treatment of breast cancer, mainly for the most aggressive type with limited targeted therapies such as triple-negative breast cancer (TNBC). We recently generated conjugated polymer nanoparticles (CPNs) as efficient photosensitizers for the photo-eradication of different cancer cells. With the aim of improving the selectivity of PDT with CPNs, the nanoparticle surface conjugation with unique 2’-Fluoropyrimidines-RNA-aptamers that act as effective recognition elements for functional surface signatures of TNBC cells was proposed and designed. A coupling reaction with carbodiimide was used to covalently bind NH2-modified aptamers with CPNs synthetized with two polystyrene-based polymer donors of COOH groups for the amide reaction. The selectivity of recognition for TNBC membrane receptors and PDT efficacy were assayed in TNBC cells and compared with non-TNBC cells by flow cytometry and cell viability assays. Furthermore, in vitro PDT efficacy was assayed in different TNBC cells with significant improvement results using CL4, sTN29 and sTN58 aptamers compared to unconjugated CPNs and SCR non-specific aptamer. In a chemoresistance TNBC cell model, sTN58 was the candidate for improving labelling and PDT efficacy with CPNs. We proposed sTN58, sTN29 and CL4 aptamers as valuable tools for selective TNBC targeting, cell internalization and therapeutic improvements for CPNs in PDT protocols.

Highlights

IntroductionAccording to the International Agency for Research on Cancer, an estimated 19.3 million new cancer cases and almost 10 million cancer-related deaths occurred in 2020 [1]
This article is an open access articleAccording to the International Agency for Research on Cancer, an estimated 19.3 million new cancer cases and almost 10 million cancer-related deaths occurred in 2020 [1]
Nanomedicine brings numerous innovative materials to develop multifunctional nanosystems for the diagnosis and treatment of several types of cancer and is revolutionizing the delivery and enhancing the effectiveness of biologically active molecules [6]. This postulation is valid when biological moieties are identified for specific tumor recognition, and in our case the development of selective triple-negative breast cancer (TNBC) targeting agents would greatly advance the development of personalized therapy for the most aggressive type of breast cancer, and where the specific treatments employed for other subtypes of breast cancer have no place

Summary

Introduction

According to the International Agency for Research on Cancer, an estimated 19.3 million new cancer cases and almost 10 million cancer-related deaths occurred in 2020 [1]. Breast cancer is the leading cause of cancer-related deaths among women globally and has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%) [1]. Pharmaceutics 2022, 14, 626 is the deadliest form because it is more aggressive, usually diagnosed at a later stage and more likely to develop recurrence after conventional treatments [2]. Chemotherapy remains the mainstay of treatment for TNBC patients; it involves issues such as high toxicity and high failure rate due to the induced non-specific distribution of drugs and rapidly acquired drug resistance [4,5]. There is a need for new therapeutic compounds or treatments to eliminate, in a more selective way, TNBC tumor cells

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