Redox chemistry-enabled stepwise surface dual nanoparticle engineering of 2D MXenes for tumor-sensitive T1 and T2 MRI-guided photonic breast-cancer hyperthermia in the NIR-II biowindow.

With the fast advent of two-dimensional (2D) MXenes, several therapeutic paradigms based on 2D MXenes flourish, but a generic strategy for MXene functionalization to achieve theranostic functionalities and desirable performance is still lacking. In this work, we report a facile and efficient stepwise surface-functionalization strategy to achieve distinct tumor microenvironment (TME)-responsive T1 and T2 magnetic resonance (MR) imaging-guided photothermal breast-cancer hyperthermia in the second near-infrared (NIR-II) biowindow. This approach is based on the stepwise growth of superparamagnetic Fe3O4 and paramagnetic MnOx nanocomponents onto the large surface of ultrathin 2D niobium carbide (Nb2C) MXene nanosheets (Fe3O4/MnOx-Nb2C) by making full use of the redox status/chemistry of the 2D MXene surface. Such a surface-nanoparticle engineering strategy endows Fe3O4/MnOx-Nb2C composite nanosheets with a series of properties that include high photothermal-conversion efficiency in the NIR-II biowindow (1064 nm, η 30.9%) for effective photothermal tumor eradication without further reoccurrence. It also allows TME-responsive T1- and T2-weighted MR imaging and high biocompatibility for guaranteeing further potential clinical transformation. This work not only makes the efficient diagnostic T1- and T2-weighted MR imaging-guided photonic hyperthermia of breast cancer possible, but also broadens the biomedical applications of MXene-based nanoplatforms by developing novel surface-engineering strategies to construct 2D Nb2C MXene-based composite multifunctional nanoplatforms.

Defect engineering of 2D BiOCl nanosheets for photonic tumor ablation.

Photothermal therapy (PTT) is an emerging technology as a noninvasive therapeutic modality for inducing photonic cancer hyperthermia. However, current photothermal conversion agents suffer from low therapeutic efficiency and single functionality. Engineering crystal defects on the surface or substrate of semiconductors can substantially enhance their optical absorption capability as well as improve their photothermal effects in theranostic nanomedicines. In this study, a specific defect engineering strategy was developed to endow two-dimensional (2D) BiOCl nanosheets with intriguing photothermal conversion performance by creating oxygen vacancies on the surface (O-BiOCl). Importantly, the photothermal performance and photoacoustic imaging capability of the 2D O-BiOCl nanosheets could be precisely controlled by modulating the amounts of oxygen vacancies. The strong Bi-based X-ray attenuation coefficient endowed these nanosheets with the contrast-enhanced computed tomography imaging capability. The high near-infrared-triggered photonic hyperthermia for tumor ablation was systematically demonstrated both in vitro at the cellular level and in vivo for tumor breast cancer mice xenograft models. Based on the demonstrated high biocompatibility of these 2D O-BiOCl nanosheets, this work not only formulates an intriguing 2D photothermal nanoagent for tumor ablation, but also provides an efficient strategy to control the photothermal performance of nanoagents by defect engineering.

Clearable Theranostic Platform with a pH-Independent Chemodynamic Therapy Enhancement Strategy for Synergetic Photothermal Tumor Therapy.

Chemodynamic therapy (CDT) is an emerging field, which utilizes intratumoral iron-mediated Fenton chemistry for cancer therapy. However, the slightly acidic tumor environment is improper for the classical Fenton reaction, which is generally energetic in a narrow pH range (e.g., pH = 3-4). Herein, a kind of ultrasmall bovine serum albumin (BSA)-modified chalcopyrite nanoparticles (BSA-CuFeS2 NPs) was synthesized via a facile aqueous biomineralization strategy, which shows high dispersity and biocompatibility. Interestingly, the obtained BSA-CuFeS2 shows a pH-independent Fenton-like reaction, which could exert Fenton-like activity to efficiently generate •OH under a weak acidic tumor environment. Combined with the extraordinarily high photothermal conversion (38.8%), BSA-CuFeS2 shows the synergistic function of high photothermal therapy (PTT) and enhanced CDT, that is, PTT/CDT. Importantly, such ultrasmall BSA-CuFeS2 NPs measuring around 4.9 nm can be quickly cleared out of the body through kidneys and liver, thus effectively avoiding long-term toxicity and systemic toxicity. Moreover, BSA-CuFeS2 NPs can act as an efficient T2-weighted magnetic resonance imaging (MRI) contrast agent to guide tumor ablation in vivo. This work offers a universal approach to boost production •OH by a pH-independent Fenton-like reaction strategy and achieves MRI-guided synergistic enhanced photothermal-CDT for highly efficient tumor treatment.

Theranostic 2D ultrathin MnO2 nanosheets with fast responsibility to endogenous tumor microenvironment and exogenous NIR irradiation.

The fabrication of functional nanoparticles with unique ultra-sensitivity to endogenous tumor microenvironment (TME) is of great significance for their improved theranostic performance and easy excretion out of the body, which has not been realized among diverse nano-sized photothermal agents for photothermal therapy (PTT) of tumor. In this work, we report on the synthesis of 2D ultrathin MnO2 nanosheets for highly efficient PTT against tumor with ultra-sensitivity to endogenous TME. These ultrathin 2D MnO2 nanosheets show the intriguing characteristic of disintegration and releasing of Mn2+ in response to the mild acidic condition and elevated reducing microenvironment of TME, which has successfully realized the pH- and reducing-responsive T1-weighted magnetic resonance imaging of tumor. Importantly, the high PTT efficiency of 2D MnO2 nanosheets responsive to exogenous NIR irradiation has been systematically demonstrated both in vitro and in vivo for suppressing the tumor growth. This first report on the exploring of TME-sensitive photothermal agents with concurrent diagnostic and therapeutic (theranostic) functions significantly broadens the biomedical application of 2D functional biomaterials, which also promotes the further potential clinical translations of nano-sized photothermal agents.

Electroacupuncture prevents cognitive impairments by regulating the early changes after brain irradiation in rats.

Cognitive impairments severely affect the quality of life of patients who undergo brain irradiation, and there are no effective preventive strategies. In this study, we examined the therapeutic potential of electroacupuncture (EA) administered immediately after brain irradiation in rats. We detected changes in cognitive function, neurogenesis, and synaptic density at different time points after irradiation, but found that EA could protect the blood-brain barrier (BBB), inhibit neuroinflammatory cytokine expression, upregulate angiogenic cytokine expression, and modulate the levels of neurotransmitter receptors and neuropeptides in the early phase. Moreover, EA protected spatial memory and recognition in the delayed phase. At the cellular/molecular level, the preventative effect of EA on cognitive dysfunction was not dependent on hippocampal neurogenesis; rather, it was related to synaptophysin expression. Our results suggest that EA applied immediately after brain irradiation can prevent cognitive impairments by protecting against the early changes induced by irradiation and may be a novel approach for preventing or ameliorating cognitive impairments in patients with brain tumors who require radiotherapy.

A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy.

To integrate photothermal ablation (PTA) with radiotherapy (RT) for improved cancer therapy, we constructed a novel multifunctional core/satellite nanotheranostic (CSNT) by decorating ultrasmall CuS nanoparticles onto the surface of a silica-coated rare earth upconversion nanoparticle. These CSNTs could not only convert near-infrared light into heat for effective thermal ablation but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage both in vitro and in vivo. With the synergistic interaction between PTA and the enhanced RT, the tumor could be eradicated without visible recurrence in 120 days. Notably, hematological analysis and histological examination unambiguously revealed their negligible toxicity to the mice within a month. Moreover, the novel CSNTs facilitate excellent upconversion luminescence/magnetic resonance/computer tomography trimodal imagings. This multifunctional nanocomposite is believed to be capable of playing a vital role in future oncotherapy by the synergistic effects between enhanced RT and PTA under the potential trimodal imaging guidance.