Triple-Modal Imaging-Guided Chemo-Photothermal Synergistic Therapy for Breast Cancer with Magnetically Targeted Phase-Shifted Nanoparticles

Abstract

Current nanodrug-based cancer therapy is susceptible to the problems of rapid clearance from circulation and limited therapeutic efficacy. Herein, we report a magnetically targeted and photothermal-triggered drug release nanotheranostics system based on superparamagnetic iron oxide (Fe3O4), IR780, doxorubicin (DOX), and perfluoropentane (PFP) entrapped poly-lactide-co-glycolide (PLGA) nanoparticles (IR780/Fe3O4@PLGA/PFP/DOX NPs) for triple-modal imaging-guided synergistic therapy of breast cancer. In this work, IR780 and Fe3O4 convert light into heat, which triggers DOX release from IR780/Fe3O4@PLGA/PFP/DOX NPs and a phase-shift thermoelastic expansion of PFP; this procedure further accelerates the DOX release and tissue extrusion deformation. Fe3O4 NPs also serve as the target moiety by an external magnet directed to the tumor. Specifically, the IR780/Fe3O4@PLGA/PFP/DOX NPs can be used for triple-modal imaging, including near infrared fluorescence, magnetic resonance, and ultrasound. Furthermore, the antitumor therapy studies reveal the extraordinary performance of IR780/Fe3O4@PLGA/PFP/DOX NPs in magnetically targeted synergistic chemo-photothermal therapy of cancer. Therefore, the multifunctional IR780/Fe3O4@PLGA/PFP/DOX NPs guided by the magnetic field show a great potential for cancer theranostics.

Near-infrared-induced IR780-loaded PLGA nanoparticles for photothermal therapy to treat breast cancer metastasis in bones

“…2,[7][8][9] Therapies exist for breast cancer metastasis to bone, such as surgery and chemotherapy; however, these therapies have distinct disadvantages. [10][11][12] Surgery is only suitable for removing primary lesion tumours that are well-dened; it is not an ideal approach for the treatment of small and poorly dened metastases. 11 Also, the problem of the poor weight-bearing of the remaining bones still remains.…”

“…[10][11][12] Surgery is only suitable for removing primary lesion tumours that are well-dened; it is not an ideal approach for the treatment of small and poorly dened metastases. 11 Also, the problem of the poor weight-bearing of the remaining bones still remains. 13 Chemotherapy, which is the most widely applied therapy for bone metastases, possesses the advantages of less injury than surgery and greater suitability for the middle and late stages of breast cancer; however, it is still substantially limited by high visceral toxicity and drug resistance, 11 and the high risk of cancer relapse also remains.…”

“…Nanomedicines, which have been used in therapy, including gene therapy, radiotherapy, chemotherapy and photothermal therapy (PTT), are a considerable innovation for cancer therapy. 11,18 Recently, due to its minimized invasiveness, improved preservation of the surrounding tissues and high anti-tumour efficiency compared with traditional treatments, 19,20 near-infrared (NIR) laser-induced PTT has attracted increasing attention as an emerging strategy for the local treatment of tumours by generating high temperatures in tissues, thus leading to more precise damage to the targeted regions. 5,18,21 NIR laser-induced PTT uses photo-absorbance to transform light energy into heat to "burn" cancer cells.…”

“…5,18,21 NIR laser-induced PTT uses photo-absorbance to transform light energy into heat to "burn" cancer cells. 11,22 Several nanomaterials have been developed as PTT agents due to their excellent NIR light-absorption properties. 11,12,19 However, some of these nanomaterials are potentially toxic due to poor biodegradability and biocompatibility, inevitably limiting their clinical applications.…”

“…11,22 Several nanomaterials have been developed as PTT agents due to their excellent NIR light-absorption properties. 11,12,19 However, some of these nanomaterials are potentially toxic due to poor biodegradability and biocompatibility, inevitably limiting their clinical applications. 19,23 Thus, it is important to develop a biodegradable photoabsorbent for biologically safe NIR laser-induced PTT.…”