Abstract

Simple SummaryThe purpose of this work was to evaluate the development of polymer-based nanoparticles that can both generate heat and be used for fluorescence detection. The nanoparticles were used against luminescent colorectal cancer cells that were either sensitive or resistant to the chemotherapy drug, oxaliplatin. The fluorescence of the nanoparticles indicates that they are internalized within the cells for heat generation. Mild heating makes oxaliplatin-resistant cancer cells responsive to chemotherapy, and the nanoparticle-induced hyperthermia causes cell death in a few minutes, compared to classical bulk heating, which takes a few hours. Changes in the luminescence of the cancer cells can be used to determine the thermal dose induced by the nanoparticles, which may be correlated with the cell viability and therapeutic response.Oxaliplatin plays a significant role as a chemotherapeutic agent for the treatment of colorectal cancer (CRC); however, oxaliplatin-resistant phenotypes make further treatment challenging. Here, we have demonstrated that rapid (60 s) hyperthermia (42 °C), generated by the near-infrared stimulation of variable molecular weight nanoparticles (VMWNPs), increases the effectiveness of oxaliplatin in the oxaliplatin-resistant CRC cells. VMWNP-induced hyperthermia resulted in a higher cell death in comparison to cells exposed to chemotherapy at 42 °C for 2 h. Fluorescence from VMWNPs was observed inside cells, which allows for the detection of CRC. The work further demonstrates that the intracellular thermal dose can be determined using cell luminescence and correlated with the cell viability and response to VMWNP-induced chemotherapy. Mild heating makes oxaliplatin-resistant cancer cells responsive to chemotherapy, and the VMWNPs-induced hyperthermia can induce cell death in a few minutes, compared to classical bulk heating. The results presented here lay the foundation for photothermal polymer nanoparticles to be used for cell ablation and augmenting chemotherapy in drug-resistant colorectal cancer cells.

Highlights

  • Introduction published maps and institutional affilColorectal cancer (CRC) is the fourth leading cause of cancer-related deaths, with few available treatment options [1,2,3]

  • Quantum yield (QY) is a useful measurement to gauge the fluorescence of nanoparticles, and we have previously found the QY of oligomeric NPs to be 0.27 and variable molecular weight nanoparticles (VMWNPs) to be 0.077, which, low in value, allows for fluorescence detection in vitro [28]

  • VMWNPs were utilized for hyperthermia generation to augment chemotherapy in

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Summary

Introduction

Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths, with few available treatment options [1,2,3]. Recent clinical studies showed that hyperthermia (39–42 ◦ C) is an effective adjuvant therapeutic technique along with radiotherapy and/or chemotherapy, and that 42 ◦ C is routinely used clinically with intraperitoneal chemotherapy for the treatment of CRC [4,5,6,7,8,9]. Among the available chemotherapeutic drugs, oxaliplatin is a cornerstone for the treatment of CRC. In order to improve the precision of the technique, instead of using a bulk carrier fluid along with a heat exchanger in the traditional hyperthermia iations

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