NIR‐II Excitation Phototheranostic Platform for Synergistic Photothermal Therapy/Chemotherapy/Chemodynamic Therapy of Breast Cancer Bone Metastases

Abstract

To improve bone metastases treatment efficacy, current strategies are focused on the integration of chemotherapy with phototheranostic. However, the success of phototheranostic approaches is hampered by the limited tissue penetration depth of near-infrared-I (NIR-I) light (700-900 nm). In this study, a NIR-II (1000-1700 nm) excitation phototheranostic (BTZ/Fe 2+ @BTF/ALD) is presented for NIR-II fluorescence imaging and NIR-II photoacoustic imaging-guided NIR-II photothermal therapy (PTT), chemotherapy, and chemodynamic therapy (CDT) of breast cancer bone metastases. This phototheranostic is developed by integrating a dopamine-modified NIR-II absorbing donor-acceptor-donor small molecule (BBT-FT-DA), the boronate anticancer drug bortezomib (BTZ), and Fe 2+ ions, as CDT catalysts, into an amphiphilic PEGylated phospholipid modified with the bone-targeting ligand alendronate. In acidic and hydrogen peroxide (H 2 O 2 ) over expression tumor microenvironment, the boronate-catechol linkage is cleaved and BTZ and Fe 2+ ions are released to initiate the Fenton reaction, that is, chemotherapy and CDT, respectively, are initialized. It is confirmed using the murine 4T1 bone metastasis model that BTZ/Fe 2+ @BTF/ALD significantly suppresses the progression of tumor cells in the bone tissue via a synergistic NIR-II PTT/chemotherapy/CDT effect. Overall, this work provides fresh insights to guide the development of NIR-II phototheranostics for breast cancer bone metastases.

Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions

“…(B) Schematic illustration of 1064 nm light-activated NIR-II phototheranostic nanoplatform (BTZ/Fe2+@BTF/ALD) for combined NIR-II PTT/chemotherapy/CDT of breast cancer bone metastases. Reproduced under the terms of the http://creativecommons.org/licenses/by/4.0/ License 221 , published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.…”

“…In order to improve the therapeutic effect of bone metastases, the current treatment strategy mainly focuses on the combination of chemotherapy and phototherapy, in order to overcome the limited tissue penetration depth of NIR-I light, Professor Fan et al jointly reported a phototherapy nanoparticle (BTZ/Fe 2+ @BTF/ALD) for NIR-II fluorescence imaging and NIR-II photoacoustic imaging-guided NIR-II PTT, chemotherapy and CDT of breast cancer bone metastasis 221 . This phototherapy was performed by integrating dopamine-modified NIR-II absorption of donor-receptor-donor small molecules (BBT-FT-DA), borate anticancer drug Bortezomib (BTZ), and Fe 2+ as CDT catalysts into a bone-targeted ligand alendronate modified amphiphilic pegylated phospholipid.…”

Effective Nanocomposite Based on Bi2MoO6/MoS2/AuNRs for NIR-II Light-Boosted Photodynamic/Chemodynamic Therapy

“…8,9 However, the conventional PDT effect depends greatly on the PS, which is usually activated by UV or visible light that has low tissue penetration and high phototoxicity. In contrast, near-infrared (NIR) light, which can be divided into two biological windows, i.e., the first NIR (NIR-I: 700−950) and the second NIR (NIR-II: 1000−1700) biological windows, 10,11 has a higher tissue penetration depth owing to the low scattering and absorption of light by body tissues. 12 Therefore, the development of new PS agents that absorb the light in the NIR range is one of the highly pursued goals in PDT, while the CDT depends on the Fenton/Fentonlike reaction or is based on the catalysis of the materials that can decompose hydrogen peroxide (H 2 O 2 ) to hydroxyl radical (•OH) and 1 O 2 , which enhances the PDT effect.…”

“…PDT effect relies on the photosensitizer (PS), which converts the oxygen (O 2 ) to toxic ROS, especially singlet oxygen ( 1 O 2 ), which oxidizes the cancer cell and leads to cell death upon the light irradiation with an appropriate wavelength. , However, the conventional PDT effect depends greatly on the PS, which is usually activated by UV or visible light that has low tissue penetration and high phototoxicity. In contrast, near-infrared (NIR) light, which can be divided into two biological windows, i.e., the first NIR (NIR-I: 700–950) and the second NIR (NIR-II: 1000–1700) biological windows, , has a higher tissue penetration depth owing to the low scattering and absorption of light by body tissues . Therefore, the development of new PS agents that absorb the light in the NIR range is one of the highly pursued goals in PDT, while the CDT depends on the Fenton/Fenton-like reaction or is based on the catalysis of the materials that can decompose hydrogen peroxide (H 2 O 2 ) to hydroxyl radical (•OH) and 1 O 2 , which enhances the PDT effect. − Nevertheless, the low catalytic efficiency and off-target side effect of the Fenton reaction limit the biomedical application of CDT .…”

Self-Assembled Aza-BODIPY and Iron(III) Nanoparticles for Photothermal-Enhanced Chemodynamic Therapy in the NIR-II Window

“…It has been verified that heat can accelerate the Fenton reaction for amplified CDT. − Thus, combining PTT with CDT may achieve greater therapeutic outcomes. However, the construction of organic materials doped with metal ions for chemodynamic–photothermal combined therapy has been limited to a number of studies, which mainly focused on NIR-I. − …”