Rationale: The development of a highly effective and tumor-specific therapeutic strategy, which can act against the primary tumor and also condition the host immune system to eliminate distant tumors, remains a clinical challenge. Methods: Herein, we demonstrate a facile yet versatile ZnO-capping and Doxorubicin (DOX)-loaded multifunctional nanocomposite (AuNP@mSiO 2 @DOX-ZnO) that integrates photothermal properties of gold nanoparticles (NPs), pH-responsive properties and preferential selectivity to tumor cells of ZnO QDs and chemotherapeutic agent into a single NP. The photothermal performance, pH-triggered release and preferential phagocytic ability were assessed. The induced anti-tumor immunity was determined by analyzing immune cell profile in tumor in vivo and molecular mechanism were identified by detecting expression of immunogenic cell death (ICD) markers in vitro . Moreover, mice models of unilateral and bilateral subcutaneous melanoma and lung metastasis were established to evaluate the antitumor effects. Results: As an efficient drug carrier, ZnO-capped NPs guarantee a high DOX payload and an in vitro , efficient release of at pH 5.0. In murine melanoma models, the nanocomposite can significantly inhibit tumor growth for a short period upon low-power laser irradiation. Importantly, ZnO NPs not only demonstrate preferential selectivity for melanoma cells but can also induce ICD. Meanwhile, AuNP@mSiO 2 -based photothermal therapy (PTT) and DOX are directly cytotoxic towards cancer cells and demonstrate an elevated ICD effect. The induced ICD promotes maturation of dendritic cells, further stimulating the infiltration of effector T cells into tumor sites, preventing tumor growth and distant lung metastases. Conclusions: This study highlights the novel mechanism of ZnO-triggered anti-tumor immunity via inducing ICD. Additionally, we shed light on the multifunctionality of nanocomposites in delivering localized skin tumor therapy as well as inhibiting metastatic growth, which holds great promise in clinical applications.
Background: Hyaluronic acid soft-tissue augmentation fillers are commonly injected into multiple areas of the face, including the tear trough. Despite well-documented risks, there is no standardized, evidence-based approach to inject filler in this area, be it using a hypodermic needle or a microcannula. The authors, therefore, sought to establish a preference between the two methods to facilitate progression toward standardization and prevention of adverse events. Methods: This is a systematic review of articles discussing hyaluronic acid tear trough injection techniques performed in vivo and related outcomes. Searches were conducted across The Cochrane Library, PubMed, Scopus, Web of Science, and Embase to yield relevant articles published before February of 2020. All selected articles incorporated discrete patient cases and were analyzed by a variety of variables assessing evidence strength, outcomes, technique, and patient safety. Results: After appraisal, 42 articles met eligibility criteria: 20 using needles, 12 using cannulas, and 10 focusing on adverse events. Level III was the most commonly awarded evidence grade, corresponding to retrospective, nonexperimental descriptive studies. There were no statistically significant differences in reported aesthetic results, patient satisfaction, or incidence of adverse events across the needle-based and cannula-based articles. Some technique trends, such as targeted anatomical plane and needle position, emerged in subsequent articles. Conclusion: Given that there were no statistically significant differences in patient safety or outcomes, an evidence-based preference for needle or cannula injection into the tear trough cannot be made at this time. Current inconsistencies make tear trough injection procedures difficult to replicate, making standardization based on avoidance of adverse events not feasible.
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