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Near‐infrared II (NIR‐II) fluorescent nanoparticles (NPs) based on aggregation‐induced emission (AIE) have attracted significant attention due to their multimodal imaging capabilities as well as the combined photothermal and photodynamic therapeutic effects in cancer therapy. Reported herein is the rational designed AIE molecule (BPT), via incorporating phenothiazine units with strong electron‐donating and reactive oxygen species (ROS) generation capabilities into the classical AIE scaffold tetraphenylethylene, further coupled with a strong electron‐acceptor named benzo[1,2‐c:4,5‐c']bis[1,2,5]thiadiazole. The BPT NPs exhibited maximum NIR‐II fluorescence emission at 1083 nm, a fluorescence quantum yield of 1.53%, photothermal conversion efficiency of 63%, and photoacoustic imaging capabilities, alongside considerable type I ROS generation ability. Additionally, when a kind of nitric oxide (NO) donor named O2‐(2,4‐dinitrophenyl) 1‐[(4‐ethoxycarbonyl) piperazin‐1‐yl]diazen‐1‐ium‐1,2‐diolate (JSK) was incorporated, the corresponding JSK‐BPT NPs could generate O2−, NO, and peroxynitrite to induce phototoxicity. By applying it to the 4T1 breast tumor model, JSK‐BPT NPs achieved high‐quality multimodal imaging of the vasculature and tumor regions in mice. Under the multimodal imaging guidance, the 4T1 tumor could be ablated completely after a single dose of JSK‐BPT NPs and under the irradiation of an 808 nm laser. Reported herein is the rational‐designed aggregation‐induced emission molecule (BPT), its nanoparticles (BPT NPs), and further processed heat and peroxynitrite generating nanoplatform for precision multimodal imaging‐guided tumor phototherapy. This nanoplatform showed near‐infrared II fluorescence, photothermal, and photoacoustic imaging capabilities, together with efficient heat production and multiple reactive oxygen species generation capacities, achieving complete tumor ablation with a single dose under the guidance of tri‐modal imaging in the 4T1 mouse tumor model.

This study evaluated whether the addition of a monoclonal antibody against the tumor-associated disialoganglioside GD2, in combination with GM-CSF and interleukin-2, to standard therapy consisting of isotretinoin alone improved outcomes in children with high-risk neuroblastoma. Neuroblastoma, a cancer of the sympathetic nervous system responsible for 12% of deaths associated with cancer in children under 15 years of age, 1 is a heterogeneous disease, with nearly 50% of patients having a high-risk phenotype characterized by widespread dissemination of the cancer and poor long-term survival, even if intensive multimodal treatments are used. 2 The initial results of the last randomized, controlled trial showing a significant improvement in outcomes were published over a decade ago 3 , 4 and established the standard therapy for high-risk neuroblastoma: myeloablative therapy with stem-cell rescue, followed by the treatment of minimal residual disease with isotretinoin. However, . . .

To meet the high requirements of biomedical applications in antimicrobial agents, it is crucial to explore efficient nano‐antimicrobial agents with no resistance and good biocompatibility for treating infected wounds. In this study, composite nano‐antibiotic TPA‐Py@AuNCs⊂BSA nanoparticles (TAB NPs) are prepared using hollow mesoporous Au nanocages (AuNCs) loaded with a photosensitizer (namely TPA‐Py) with D‐π‐A structure showing aggregation‐induced emission properties. When TPA‐Py is encapsulated in the cavity of AuNCs, its fluorescence is suppressed. In the presence of photothermal induction, TPA‐Py can be released from the AuNCs, allowing for the restoration of fluorescence illumination and the specific imaging of Gram‐positive bacteria. TAB NPs demonstrate outstanding antimicrobial activity against a variety of bacteria, and this multimodal antimicrobial property does not lead to the development of bacterial resistance. In vitro experiments show that TAB NPs could eliminate bacteria and ablate bacterial biofilm. In vivo experiments show that the synergistic antimicrobial effect of TAB NPs has a significant positive impact on the treatment of infected wounds, including rapid antibacterial action, promotion of M2 macrophage polarization, and enhancement of chronic wound healing. This study provides an effective strategy for developing wide‐spectrum nano‐antibiotics for the ablation of bacterial biofilms and the treatment of infected wounds. Here, the composite nano‐antibiotic TPA‐Py@AuNCs⊂BSA exhibit remarkable antibacterial activity against Escherichia coli, Staphylococcus aureus, and Methicillin‐resistant Staphylococcus aureus, harnessing synergistic photodynamic, photothermal, physical, and ionic effects. Both in vitro and in vivo experiments have validated the efficacy of TPA‐Py@AuNCs⊂BSA nanoparticles in eliminating bacteria, ablating biofilms, and treating infected wounds.

Background Since the “War on Cancer” was declared in 1971, the United States alone has expended some $300 billion on research, with a heavy focus on the role of genomics in anticancer therapy. Voluminous data have been collected and analyzed. However, in hindsight, any achievements made have not been realized in clinical practice in terms of overall survival or quality of life extended. This might be justified because cancer is not one disease but a conglomeration of multiple diseases, with widespread heterogeneity even within a single tumor type. Discussion Only a few types of cancer have been described that are associated with one major signaling pathway. This enabled the initial successful deployment of targeted therapy for such cancers. However, soon after this targeted approach was initiated, it was subverted as cancer cells learned and reacted to the initial treatments, oftentimes rendering the treatment less effective or even completely ineffective. During the past 30 plus years, the cancer classification used had, as its primary aim, the facilitation of communication and the exchange of information amongst those caring for cancer patients with the end goal of establishing a standardized approach for the diagnosis and treatment of cancers. This approach should be modified based on the recent research to affect a change from a service-based to an outcome-based approach. The vision of achieving long-term control and/or eradicating or curing cancer is far from being realized, but not impossible. In order to meet the challenges in getting there, any newly proposed anticancer strategy must integrate a personalized treatment outcome approach. This concept is predicated on tumor- and patient-associated variables, combined with an individualized response assessment strategy for therapy modification as suggested by the patient’s own results. As combined strategies may be outcome-orientated and integrate tumor-, patient- as well as cancer-preventive variables, this approach is likely to result in an optimized anticancer strategy. Summary Herein, we introduce such an anticancer strategy for all cancer patients, experts, and organizations: Imagine a World without Cancer .

Multimodal therapy approaches that combine interventions aimed at different aspects of disease are emerging as potential-and perhaps essential-ways to enhance clinical outcomes for patients with psychiatric and neurological disorders. In order to examine the general principles underlying multimodal therapies and to explore challenges, potential barriers, and opportunities for their development, the National Academies of Sciences, Engineering, and Medicine convened a workshop in June 2016. Participants explored scientific, clinical, regulatory, and reimbursement issues related to multimodal approaches and potential opportunities to enhance clinical outcomes for individuals with nervous system disorders. This publication summarizes the presentations and discussions from the workshop.

Rheumatoid arthritis (RA) is an autoimmune disease with multifactorial etiology and intricate pathogenesis. In RA, repeated monotherapy is frequently associated with inadequate efficacy, drug resistance, and severe side effects. Therefore, a shift has occurred in clinical practice toward combination therapy. However, conventional combination therapy encounters several hindrances, including low selectivity to arthritic joints, short half-lives, and varying pharmacokinetics among coupled drugs. Emerging nanotechnology offers an incomparable opportunity for developing advanced combination therapy against RA. First, it allows for co-delivering multiple drugs with augmented physicochemical properties, targeted delivery capabilities, and controlled release profiles. Second, it enables therapeutic nanomaterials development, thereby expanding combination regimens to include multifunctional nanomedicines. Lastly, it facilitates the construction of all-in-one nanoplatforms assembled with multiple modalities, such as phototherapy, sonodynamic therapy, and imaging. Thus, nanotechnology offers a promising solution to the current bottleneck in both RA treatment and diagnosis. This review summarizes the rationale, advantages, and recent advances in nano-empowered combination therapy for RA. It also discusses safety considerations, drug–drug interactions, and the potential for clinical translation. Additionally, it provides design tips and an outlook on future developments in nano-empowered combination therapy. The objective of this review is to achieve a comprehensive understanding of the mechanisms underlying combination therapy for RA and unlock the maximum potential of nanotechnology, thereby facilitating the smooth transition of research findings from the laboratory to clinical practice.

Abstract Background Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignancy lacking a standardized treatment approach. Multimodal strategies such as chemotherapy plus surgery (CT + S) or chemotherapy plus radiotherapy (CT + RT) are commonly employed, but comparative evidence remains limited and inconsistent. Methods We retrospectively analyzed 491 patients with pathologically confirmed SCCE from 2 independent cohorts: a Chinese single-center cohort (n = 333) and the U.S. SEER database (n = 158). Patients who received monotherapy or multimodal treatment (CT + S or CT + RT) were eligible. Overall survival (OS) was evaluated using Kaplan–Meier analysis and Cox proportional hazards models. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to adjust for baseline confounders. Subgroup analyses explored potential effect modifiers. Results Multimodal therapy was associated with significantly improved OS compared to monotherapy in both cohorts (China: HR = 0.719, 95% CI: 0.561-0.922, P = .009; SEER: HR = 0.626, 95% CI: 0.417-0.938, P = .023). Among patients receiving multimodal therapy, no significant OS difference was observed between CT + S and CT + RT (P > .05), both before and after adjustment by PSM and IPTW. Subgroup analyses revealed no significant interactions between treatment strategy and clinical variables such as age, sex, tumor location, or disease stage. Conclusions Multimodal therapy improves survival over monotherapy in SCCE. CT + S and CT + RT offer comparable effectiveness, supporting their clinical interchangeability and broader use in individualized treatment planning.

The standard clinical technique for using repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder (MDD) is associated with limited efficacy to date. Such limited efficacy may be due to reliance on scalp-based targeting rather than state-of-the-science methods which incorporate fMRI-guided neuronavigation based on a specific model of neurocircuit dysfunction. In this review, we examine such a specific model drawn from regulatory focus theory, which postulates two brain/behavior systems, the promotion and prevention systems, underlying goal pursuit. Individual differences in these systems have been shown to predict vulnerability to MDD as well as to comorbid generalized anxiety disorder (GAD). Activation of an individual's promotion or prevention goals via priming leads to motivational and affective responses modulated by the individual's appraisal of their progress in attaining the goal. In addition, priming promotion vs. prevention goals induces discriminable patterns of brain activation that are sensitive to the effects of depression and anxiety: MDD is associated with promotion system failure, anhedonic/dysphoric symptoms, and hypoactivation in specific regions in left prefrontal cortex, whereas GAD is associated with prevention system failure, hypervigilant/agitated symptoms, and hyperactivation in right prefrontal cortex (PFC). These left and right PFC locations can be directly targeted in an individualized manner for TMS. Additionally, this individually targeted rTMS can be integrated with cognitive interventions designed to activate the neural circuitry associated with promotion vs. prevention, thus allowing the neuroplasticity induced by the rTMS to benefit the systems likely to be involved in remediating depression. Targeted engagement of cortical systems involved in emotion regulation using individualized fMRI guidance may help increase the efficacy of rTMS in depression. •rTMS for depression using scalp-based targeting has shown limited efficacy to date•Using fMRI-guided neuronavigation along with a model of neurocircuit dysfunction may improve the efficacy of rTMS•In this article we introduce a model of depression drawn from regulatory focus theory•Our model allows for individually targeted rTMS that engages cortical systems involved in emotion regulation and for combining interventions targeting the same putative circuit

Glioblastoma (GBM) is the most malignant brain tumor with unmet therapeutic demand. The blood‐brain‐barrier (BBB) and tumor heterogeneity limit the treatment effectiveness of various interventions. Here, an ultrasound augmented chemo/immuno therapy for GBM using a neutrophil‐delivered nanosensitizer, is developed. The sensitizer is composed of a ZnGa2O4:Cr3+ (ZGO) core for persistent luminescence imaging and a hollow sono‐sensitive TiO2 shell to generate reactive oxygen species (ROS) for controlled drug release. Immune checkpoint inhibitor (Anti‐PD‐1 antibody) is trapped in the interior of the porous ZGO@TiO2 with paclitaxel (PTX) loaded liposome encapsulation to form ZGO@TiO2@ALP. Delivered by neutrophils (NEs), ZGO@TiO2@ALP‐NEs can penetrate through BBB for GBM accumulation. After intravenous injection, ultrasound irradiation at GBM sites initiates ROS generation from ZGO@TiO2@ALP, leading to liposome destruction for PTX and anti‐PD‐1 antibody release to kill tumors and induce local inflammation, which in‐turn attractes more ZGO@TiO2@ALP‐NEs to migrate into tumor sites for augmented and sustained therapy. The treatment enhances the survival rate of the GBM bearing mice from 0% to 40% and endows them with long‐term immuno‐surveillance for tumor recurrence, providing a new approach for precision therapy against GBM and other cancers. Delivered by neutrophils (NEs), ZGO@TiO2@ALP‐NEs can penetrate through blood‐brain‐barrier for glioblastoma (GBM) accumulation. Ultrasound irradiation at GBM sites initiates generate reactive oxygen species generation from ZGO@TiO2@ALP, leading to liposome destruction for paclitaxel and anti‐PD‐1 antibody release to kill tumor and induce local inflammation, which in‐turn attracts more ZGO@TiO2@ALP‐NEs for augmented and sustained tumor elimination.

Purpose Head and neck cancer (HNC) will be diagnosed in approximately 54,000 Americans in 2022 with more than 11,000 dying as a result. The treatment of HNC often involves aggressive multimodal therapy including surgery, radiotherapy, and systemic therapy. HNC and its treatments are associated with multiple painful and function-limiting neuromusculoskeletal and visceral long-term and late effects. Among these is head and neck lymphedema (HNL), the abnormal accumulation of protein rich fluid, in as many as 90% of survivors. Though HNL is common and potentially contributory to other function-limiting issues in this population, it is notoriously understudied, underrecognized, underdiagnosed, and undertreated. This study seeks to determine the incidence of HNC-related lymphedema diagnosis and treatment in a large US healthcare claims repository database. Methods A retrospective observational cohort design and data from an integrated US healthcare claims repository—the IBM MarketScan Commercial Claims and Encounters (CCAE) and Medicare Supplemental and Coordination of Benefits (MDCR) Databases spanning the period April 1, 2012 through March 31, 2020. Results Of the 16,654 HNC patients eligible for evaluation, 1,082 (6.5%) with a diagnosis of lymphedema were identified based on eligibility criteria. Of the 521 HNC patients evaluated for lymphedema treatment, 417 (80.0%) patients received 1.5 courses of MLD, 71 (13.6%) patients were prescribed compression garments, and 45 (8.6%) patients received an advanced pneumatic compression device. Conclusion HNL in this population of HNC survivors was underdiagnosed and treated compared with contemporary assessments HNL incidence.