Metallic Carbonitride MXene Based Photonic Hyperthermia for Tumor Therapy.

Photothermal therapy (PTT) as a noninvasive hyperthermia exhibits high potential for anti-cancer treatments. The explosion of efficient photothermal agents (PTAs) keeps developing rapidly. MXene stands out due to its intriguing structures, fantastic photodynamic properties, and good biocompatibility. However, the potential of MXenes has not been sufficiently explored in PTT. Its versatile chemical compositions of MXenes provide vast opportunities to discover new candidates. Considering that the metallic feature is mainly attributed to the metal element, anionic modulation may open a distinct avenue to propel efficient PTAs with metallic nature, which is expected for high light-harvesting over near-infrared (NIR)-I and NIR-II. As a paradigm, metal carbonitride is chosen to visualize the influences of anionic modulation. Taking advantage of electron injection from nitrogen, the distinct carbonitride Ti3 C1.15 N0.85 F0.88 O0.56 (OH)0.56 exhibits a strong NIR absorption (36.6 L g-1 cm-1 at 808 nm, 43.5 L g-1 cm-1 at 1064 nm), resulting in efficient photonic hyperthermia against tumors in vitro and in vivo. Looking through a large family of MXenes, this proof-of-principle demonstration offers a deep understanding between atomic composition and physicochemical properties, which further solidifies MXenes with all the potential for biomedical applications.

Phototherapy Facilitates Tumor Recruitment and Activation of Natural Killer T cells for Potent Cancer Immunotherapy.

Adoptively transferred natural killer T (NKT) cells confer distinct cancer surveillance without causing obvious side effects, making them a promising candidate for cancer immunotherapy. However, their therapeutic efficacy is limited by inefficient tumor infiltration and inadequate activation in an immunosuppressive tumor microenvironment. To overcome these obstacles, we develop a strategy of using photothermal therapy (PTT) to promote the antitumor ability of adoptively transferred NKT cells. The transferred NKT cells are efficiently recruited to PTT-treated tumors in response to PTT-created inflammation. Moreover, PTT treatment promotes the activation of NKT cells and enhances the NKT cell-initiated immune cascade. As a consequence, the combined therapy of PTT plus NKT cell transfer exhibits excellent growth inhibition of local tumors. Moreover, it efficiently rejects distant tumors and elicits long-term immunological memory to prevent tumor recurrence. Overall, the current study opens new paths to the clinical translation of NKT cells for cancer immunotherapy.

Pre- and post-irradiation mild hyperthermia enabled by NIR-II for sensitizing radiotherapy.

The clinical application of cancer radiotherapy is critically impeded by hypoxia-induced radioresistance, insufficient DNA damage, and multiple DNA repair mechanisms. Herein we demonstrate a dual-hyperthermia strategy to potentiate radiotherapy by relieving tumor hypoxia and preventing irradiation-induced DNA damage repair. The tumor hyperthermia temperature was well-controlled by a near infrared laser with minimal side effects using PEGylated nanobipyramids (PNBys) as the photo-transducer. PNBys have narrow longitudinal localized surface plasmon resonance peak in NIR-II window with a high extinction coefficient (2.0 × 1011 M-1 cm-1) and an excellent photothermal conversion efficiency (44.2%). PNBys-induced mild hyperthermia (MHt) prior to radiotherapy enables vessel dilation, blood perfusion, and hypoxia relief, resulting in an increased susceptibility of tumor cells response to radiotherapy. On the other hand, MHt after radiotherapy inhibits the repair of DNA damage generated by irradiation. The PNBys exert hierarchically superior antitumor effects by the combination of MHt pre- and post-radiotherapy in murine mammary tumor EMT-6 model. Consequently, different from the simple combination of RT and MHt, the coupling of pre- and post-MHt with RT by PNBys open intriguing avenues towards new promising antitumor efficacy.

Chemotaxis-driven delivery of nano-pathogenoids for complete eradication of tumors post-phototherapy.

The efficacy of nano-mediated drug delivery has been impeded by multiple biological barriers such as the mononuclear phagocyte system (MPS), as well as vascular and interstitial barriers. To overcome the abovementioned obstacles, we report a nano-pathogenoid (NPN) system that can in situ hitchhike circulating neutrophils and supplement photothermal therapy (PTT). Cloaked with bacteria-secreted outer membrane vesicles inheriting pathogen-associated molecular patterns of native bacteria, NPNs are effectively recognized and internalized by neutrophils. The neutrophils migrate towards inflamed tumors, extravasate across the blood vessels, and penetrate through the tumors. Then NPNs are rapidly released from neutrophils in response to inflammatory stimuli and subsequently taken up by tumor cells to exert anticancer effects. Strikingly, due to the excellent targeting efficacy, cisplatin-loaded NPNs combined with PTT completely eradicate tumors in all treated mice. Such a nano-platform represents an efficient and generalizable strategy towards in situ cell hitchhiking as well as enhanced tumor targeted delivery.

Near-Infrared II Phototherapy Induces Deep Tissue Immunogenic Cell Death and Potentiates Cancer Immunotherapy.

The deep and inner beds of solid tumors lack lymphocytic infiltration and are subjected to various immune escape mechanisms. Reversing immunosuppression deep within the tumor is vital in clinical cancer therapy, however it remains a huge challenge. In this work, we have demonstrated the use of a second window near-infrared (NIR(II)) photothermal treatment to trigger more homogeneous and deeper immunogenic cancer cell death in solid tumors, thereby eliciting both innate and adaptive immune responses for tumor control and metastasis prevention. Specifically, photothermal transducers with similar components, structures, and photothermal conversion efficiencies, but different absorptions in red light, NIR(I), and NIR(II) biowindows, were constructed by controlling the self-assembly of gold nanoparticles on fluidic liposomes. In vitro, photothermal treatments induced immunogenic cell death (ICD) that were accompanied by the release of damage-associated molecular patterns (DAMPs) regardless of the wavelength of incident lasers. In vivo, NIR(II) light resulted in a more homogeneous release and distribution of DAMPs in the deeper parts of the tumors. With the induction of ICD, NIR(II) photothermal therapy simultaneously triggered both innate and adaptive immune responses and enabled efficient tumor control with 5/8 of the mice remaining tumor-free in the cancer vaccination assay. Additionally, the NIR(II) photothermal treatment in combination with checkpoint blockade therapy exerted long-term tumor control over both primary and distant tumors. Finally, using systemically administered two-dimensional polypyrrole nanosheets as a NIR(II) transducer, we achieved striking therapeutic effects against whole-body tumor metastasis via a synergistic photothermal-immunological response.

Risk of Mental Disorders in Children and Adolescents With Atopic Dermatitis: A Systematic Review and Meta-Analysis.

Assessing the psychological effects on children and adolescents of suffering atopic dermatitis (AD) is essential, when planning successful management. This study aimed to systematically review the literature regarding risk of mental disorders in children and adolescents with, or without, AD; and to explore confounders. We identified potentially relevant studies from EMBASE, MEDLINE, PsycINFO, ERIC, the British Nursing Index, the Family and Society Studies Worldwide, the Social Work Abstracts, and the Sociological Abstracts from inception to Sep 30, 2018. Investigators independently screened titles and abstracts, and then full-texts. Investigators independently extracted data from included studies. Meta-analyses using random-effects models were performed, reporting odds ratios (ORs; 95% CIs). Thirty-seven studies (n = 2,068,911 children/ adolescents) were included. Meta-analysis of 35 studies found that children and adolescents with AD had significantly higher risk of total mental disorders than those without AD (OR = 1.652; 95% CI, 1.463-1.864). There was no significant difference in risks for ADHD (OR = 1.563; 95% CI, 1.382-1.769); sleep disorders (OR = 2.100; 95% CI, 1.322-3.336); anxiety (OR = 1.339; 95% CI, 1.062-1.687); depression (OR = 1.402 95% CI, 1.256-1.565); conduct disorder (OR = 1.494 95% CI, 1.230-1.815); or ASD (OR = 2.574; 95% CI, 1.469-4.510; Q b = 8.344, p = 0.138). Race/ethnicity of child, target of comparison, type of studies, representativeness of the sample, measures of AD and mental disorders were significant moderators for total mental disorders. Integrated, holistic, multidisciplinary management of pediatric AD is significantly important, which emphasizes the well-being of the whole person.

PVP intercalated metallic WSe2 as NIR photothermal agents for efficient tumor ablation.

Transition metal dichalogenides (TMDCs) with unique layered structures hold promising potential as transducers for photothermal therapy. However, the low photothermal conversion efficiency and poor stability in some cases limit their practical applications. Herein, we demonstrate the fabrication of ultrathin homogeneous hybridized TMDC nanosheets and their use for highly efficient photothermal tumor ablation. In particular, the nanosheets were composed of metallic WSe2 intercalated with polyvinylpyrrolidone (PVP), which was facilely prepared through a solvothermal process from the mixture of selenourea crystals, WCl6 powder along with PVP polymeric nanogel. Our characterizations revealed that the obtained nanosheets exhibited excellent photothermal conversion efficiency, therapeutic demonstration with improved biocompatibility and physiological stability attributing to the combined merits of metallic phase of WSe2 and hydrophilic PVP insertion. Both the histological analysis of vital organs and in vitro/in vivo tests confirmed the nanosheets as actively effective and biologically safe in this phototherapeutic technique. Findings from this non-invasive experiment clearly emphasize the explorable therapeutic efficacy of the layered-based hybrid agents in future cancer treatment planning procedures.