A Smart Hyperthermia Nanofiber-Platform-Enabled Sustained Release of Doxorubicin and 17AAG for Synergistic Cancer Therapy.

Lili Chen,Nanami Fujisawa,Mitsuhiro Ebara,Mazaya Najmina,Masato Takanohashi,Koichiro Uto

doi:10.3390/ijms22052542

Abstract

This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can achieve mutual synergy of hyperthermia, chemotherapy, and thermo-molecularly targeted therapy for highly potent therapeutic effects. The nanofiber is composed of biodegradable poly(ε-caprolactone) with doxorubicin, magnetic nanoparticles, and 17-allylamino-17-demethoxygeldanamycin. The nanofiber exhibits distinct hyperthermia, owing to the presence of magnetic nanoparticles upon exposure of the mesh to an alternating magnetic field, which causes heat-induced cell killing as well as enhanced chemotherapeutic efficiency of doxorubicin. The effectiveness of hyperthermia is further enhanced through the inhibition of heat shock protein activity after hyperthermia by releasing the inhibitor 17-allylamino-17-demethoxygeldanamycin. These findings represent a smart nanofiber system for potent cancer therapy and may provide a new approach for the development of localized medication delivery.

Highlights

Breast cancer is the most common malignancy diagnosed in women worldwide and the second leading cause of cancer-related deaths in women [1,2]
Thermal therapy, known as hyperthermia, is a mode of cancer treatment that can damage and kill cancer cells, which is employed based on evidence that indicate that cancer cells are more sensitive than normal cells to high temperatures (43–45 ◦C) [4,5,6]
PCL nanofibers containing magnetic nanoparticle (MNP), DOX, and 17AAG were fabricated through blend electrospinning

Summary

Introduction

Breast cancer is the most common malignancy diagnosed in women worldwide and the second leading cause of cancer-related deaths in women [1,2]. Despite recent advances in early diagnosis and treatment, clinical applications are still limited to single therapeutic approaches. To achieve preferable anticancer efficacy, multimodal therapies containing two or more therapeutic modalities have been extensively explored in clinical settings in the past decades. The combination therapy approach has been the preferable mode of treatment for cancer patients to significantly reduce tumor size; for example, chemotherapy is combined with gene therapy, radiotherapy, and thermal therapy [3] (Scheme 1). Thermal therapy, known as hyperthermia, is a mode of cancer treatment that can damage and kill cancer cells, which is employed based on evidence that indicate that cancer cells are more sensitive than normal cells to high temperatures (43–45 ◦C) [4,5,6]. Hyperthermia can enhance the effects of certain anticancer drugs such as salinomycin [7,8], curcumin [9], paclitaxel (PTX) [10,11] and doxorubicin (DOX) [12,13,14], increasing the susceptibility of some cancer cells to them

Methods

Results

Conclusion