Anti-lymphangiogenesis for boosting drug accumulation in tumors.

The inadequate tumor accumulation of anti-cancer agents is a major shortcoming of current therapeutic drugs and remains an even more significant concern in the clinical prospects for nanomedicines. Various strategies aiming at regulating the intratumoral permeability of therapeutic drugs have been explored in preclinical studies, with a primary focus on vascular regulation and stromal reduction. However, these methods may trigger or facilitate tumor metastasis as a tradeoff. Therefore, there is an urgent need for innovative strategies that boost intratumoral drug accumulation without compromising treatment outcomes. As another important factor affecting drug tumor accumulation besides vasculature and stroma, the impact of tumor-associated lymphatic vessels (LVs) has not been widely considered. In the current research, we verified that anlotinib, a tyrosine kinase inhibitor with anti-lymphangiogenesis activity, and SAR131675, a selective VEGFR-3 inhibitor, effectively decreased the density of tumor lymphatic vessels in mouse cancer models, further enhancing drug accumulation in tumor tissue. By combining anlotinib with therapeutic drugs, including doxorubicin (Dox), liposomal doxorubicin (Lip-Dox), and anti-PD-L1 antibody, we observed improved anti-tumor efficacy in comparison with monotherapy regimens. Meanwhile, this strategy significantly reduced tumor metastasis and elicited stronger anti-tumor immune responses. Our work describes a new, clinically transferrable approach to augmenting intratumoral drug accumulation, which shows great potential to address the current, unsatisfactory efficacies of therapeutic drugs without introducing metastatic risk.

Enhancing Vault Prediction and ICL Sizing Through Advanced Machine Learning Models.

PURPOSE: To use artificial intelligence (AI) technology to accurately predict vault and Implantable Collamer Lens (ICL) size. METHODS: The methodology focused on enhancing predictive capabilities through the fusion of machine-learning algorithms. Specifically, AdaBoost, Random Forest, Decision Tree, Support Vector Regression, LightGBM, and XGBoost were integrated into a majority-vote model. The performance of each model was evaluated using appropriate metrics such as accuracy, precision, F1-score, and area under the curve (AUC). RESULTS: The majority-vote model exhibited the highest performance among the classification models, with an accuracy of 81.9% area under the curve (AUC) of 0.807. Notably, LightGBM (accuracy = 0.788, AUC = 0.803) and XGBoost (ACC = 0.790, AUC = 0.801) demonstrated competitive results. For the ICL size prediction, the Random Forest model achieved an impressive accuracy of 85.3% (AUC = 0.973), whereas XG-Boost (accuracy = 0.834, AUC = 0.961) and LightGBM (accuracy = 0.816, AUC = 0.961) maintained their compatibility. CONCLUSIONS: This study highlights the potential of diverse machine learning algorithms to enhance postoperative vault and ICL size prediction, ultimately contributing to the safety of ICL implantation procedures. Furthermore, the introduction of the novel majority-vote model demonstrates its capability to combine the advantages of multiple models, yielding superior accuracy. Importantly, this study will empower ophthalmologists to use a precise tool for vault prediction, facilitating informed ICL size selection in clinical practice. [J Refract Surg. 2024;40(3):e126-e132.].

Disruption of Super-Enhancers in Activated Pancreatic Stellate Cells Facilitates Chemotherapy and Immunotherapy in Pancreatic Cancer.

One major obstacle in the drug treatment of pancreatic ductal adenocarcinoma (PDAC) is its highly fibrotic tumor microenvironment, which is replete with activated pancreatic stellate cells (a-PSCs). These a-PSCs generate abundant extracellular matrix and secrete various cytokines to form biophysical and biochemical barriers, impeding drug access to tumor tissues. Therefore, it is imperative to develop a strategy for reversing PSC activation and thereby removing the barriers to facilitate PDAC drug treatment. Herein, by integrating chromatin immunoprecipitation (ChIP)-seq, Assays for Transposase-Accessible Chromatin (ATAC)-seq, and RNA-seq techniques, this work reveals that super-enhancers (SEs) promote the expression of various genes involved in PSC activation. Disruption of SE-associated transcription with JQ1 reverses the activated phenotype of a-PSCs and decreases stromal fibrosis in both orthotopic and patient-derived xenograft (PDX) models. More importantly, disruption of SEs by JQ1 treatments promotes vascularization, facilitates drug delivery, and alters the immune landscape in PDAC, thereby improving the efficacies of both chemotherapy (with gemcitabine) and immunotherapy (with IL-12). In summary, this study not only elucidates the contribution of SEs of a-PSCs in shaping the PDAC tumor microenvironment but also highlights that targeting SEs in a-PSCs may become a gate-opening strategy that benefits PDAC drug therapy by removing stromal barriers.

Genomic instability and eye diseases.

Background: Genetic information is stored in the bases of double-stranded DNA. However, the integrity of DNA molecules is constantly threatened by various mutagenic agents, including pollutants, ultraviolet light (UV), and medications. To counteract these environmental damages, cells have established multiple mechanisms, such as producing molecules to identify and eliminate damaged DNA, as well as reconstruct the original DNA structures. Failure or insufficiency of these mechanisms can cause genetic instability. However, the role of genome stability in eye diseases is still under-researched, despite extensive study in cancer biology. Main text: As the eye is directly exposed to the external environment, the genetic materials of ocular cells are constantly under threat. Some of the proteins essential for DNA damage repair, such as pRb, p53, and RAD21, are also key during the ocular disease development. In this review, we discuss five ocular diseases that are associated with genomic instability. Retinoblastoma and pterygium are linked to abnormal cell cycles. Fuchs' corneal endothelial dystrophy and age-related macular degeneration are related to the accumulation of DNA damage caused by oxidative damage and UV. The mutation of the subunit of the cohesin complex during eye development is linked to sclerocornea. Conclusions: Failure of DNA damage detection or repair leads to increased genomic instability. Deciphering the role of genomic instability in ocular diseases can lead to the development of new treatments and strategies, such as protecting vulnerable cells from risk factors or intensifying damage to unwanted cells.

Self-assembly of CXCR4 antagonist peptide-docetaxel conjugates for breast tumor multi-organ metastasis inhibition.

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

Comparison of myopic astigmatic correction after cross-assisted SMILE, FS-LASIK, and transPRK.

PURPOSE: To compare astigmatic correction among cross-assisted small-incision lenticule extraction (SMILE), femtosecond laser-assisted in situ keratomileusis (FS-LASIK), and transepithelial photorefractive keratectomy (transPRK). SETTING: The Eye Hospital of Wenzhou Medical University, Zhejiang, China. DESIGN: Prospective comparison study. METHODS: 154 right eyes of 154 patients with astigmatism of -1.00 to -2.75 diopters (D) were included in this study. 64 eyes, 42 eyes, and 48 eyes were receiving SMILE, FS-LASIK, and transPRK, respectively. The SMILE group used cross-axial alignment for head positioning for astigmatism correction. In the FS-LASIK and transPRK groups, static and dynamic cyclotorsion control were used. Changes in ocular parameters and vector analysis were assessed at 6 months postoperatively. RESULTS: The safety and efficacy indices were comparable among the 3 groups at 6 months postoperatively. Residual astigmatism was smallest in the SMILE group (-0.23 ± 0.25 D) compared with that in FS-LASIK (-0.40 ± 0.28 D, P = .009) and transPRK groups (-0.42 ± 0.32 D, P = .001). 53 (82.8%), 36 (85.7%), and 37 (77.1%) eyes achieved an angle of error within ±5 degrees, respectively ( P = .55). Notably, vector analysis showed that the difference vector, the magnitude of the error, and its absolute value were significantly smaller in the SMILE group than those in the other groups ( P < .05). In addition, the higher-order aberrations, especially coma, were significantly induced postoperatively in each group ( P < .001). CONCLUSIONS: Residual astigmatism magnitude was smallest by cross-assisted SMILE, followed by FS-LASIK and transPRK, and the astigmatism axial correction was comparable among groups.

Trihelix transcription factor SlGT31 regulates fruit ripening mediated by ethylene in tomato.

Trihelix proteins are plant-specific transcription factors that are classified as GT factors due to their binding specificity for GT elements, and they play crucial roles in development and stress responses. However, their involvement in fruit ripening and transcriptional regulatory mechanisms remains largely unclear. In this study, we cloned SlGT31, encoding a trihelix protein in tomato (Solanum lycopersicum), and determined that its relative expression was significantly induced by the application of exogenous ethylene whereas it was repressed by the ethylene-inhibitor 1-methylcyclopropene. Suppression of SlGT31 expression resulted in delayed fruit ripening, decreased accumulation of total carotenoids, and reduced ethylene content, together with inhibition of expression of genes related to ethylene and fruit ripening. Conversely, SlGT31-overexpression lines showed opposite results. Yeast one-hybrid and dual-luciferase assays indicated that SlGT31 can bind to the promoters of two key ethylene-biosynthesis genes, ACO1 and ACS4. Taken together, our results indicate that SlGT31 might act as a positive modulator during fruit ripening.

Chronic Exposure to Low-Molecular-Weight Polycyclic Aromatic Hydrocarbons Promotes Lipid Accumulation and Metabolic Inflammation.

2-naphthol is a low-molecular-weight (LMW) polycyclic aromatic hydrocarbon (PAH) and air pollutant associated with childhood obesity. There has been a recent emergence of studies on the consequences of PAHs on human health. Current epidemiological reports suggest LMW-PAHs may contribute to obesity incidences in children, yet most studies focus on high-molecular-weight PAHs. This study explores 2-naphthol's impact on obesity and obesity-associated metabolic disorders. To investigate 2-naphthol's effect on lipid metabolism and inflammation, we employed 3T3-L1 and BAT1 cell lines to model white and brown adipocytes, respectively, alongside a murine macrophage cell line (RAW264.7). We found that 2-naphthol increased the expression of key adipogenic and lipogenic genes while decreasing lipolytic gene expression in chronically treated 3T3-L1 and BAT1 adipocytes. In addition, chronic 2-naphthol treatment also suppressed adrenergic-stimulated thermogenic gene expression in BAT1 brown adipocytes. In consistence, an increase in lipid accumulation was demonstrated in BODIPY and Oil Red O-stained adipocytes. Additionally, 3T3-L1 adipocytes and RAW264.7 macrophages chronically exposed to 2-naphthol showed upregulated mRNA expression of major inflammatory cytokines (e.g., tumor necrosis factor α (Tnfα), interleukin-1ß (Il-1ß), and Il-6). In summary, chronic exposure to 2-naphthol stimulates lipid accumulation in adipocytes and inflammation in adipocytes and macrophages. These findings support previous research that demonstrates 2-naphthol has obesogenic potential.

Neoisoastilbin Ameliorates Acute Gouty Arthritis via Suppression of the NF-κB/NLRP3 Pathway.

Acute gouty arthritis (AGA) is an acute inflammatory disease, whose occurrence and development mechanism are associated with inflammatory reaction of joint tissue. This study investigated the role of neoisoastilbin (NIA) in the treatment of AGA and explored the underlying mechanisms. C57BL/6 mice underwent intraarticular injection of monosodium urate (MSU) to establish an AGA model in vivo. Enzyme-linked immunosorbent assay, histopathological hematoxylin-eosin staining, western blotting, and other methods were used to observe the therapeutic effects of NIA on AGA and investigate the role of the NF-κB/NLRP3 pathway in the treatment. We found that NIA effectively reduced MSU-induced joint swelling and inflammatory cell infiltration in a concentration-dependent manner. NIA also significantly reduced interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels as compared with the respective values in the model mice group. In addition, administration of NIA significantly mitigated the phosphorylation of NF-κB-related proteins (IKKα, NF-κB, and IκBα) and the expression of NLRP3-related proteins (NLRP3, caspase-1, and ASC) in MSU-induced joint tissues. In conclusion, our research indicated that NIA significantly improved AGA, and its underlying mechanism was achieved by simultaneously inhibiting the NF-κB/NLRP3 pathway and the expression of inflammatory factors. This research preliminarily suggested the potential role of NIA in the treatment of AGA.

Modified Technique for Small-Incision Lenticule Extraction: Ye's Swing Technique.

INTRODUCTION: This study aimed to evaluate the lenticule integrity and refractive outcomes of a new technique, Ye's swing technique, during small-incision lenticule extraction (SMILE). METHODS: This prospective study enrolled patients who underwent the SMILE procedure using a modified technique for lenticule dissection. Per the standard SMILE procedure, the cap cut was opened using a hook, and an anterior dissection was performed with a counterclockwise swing, from 8 to 12 o'clock. A posterior dissection was then performed by swinging counterclockwise, leaving a thin band of the peripheral rim undissected, from 8 to 4 o'clock. The counterclockwise swing was continued to separate the edges of the rim from 4 to 12 o'clock, after which microforceps were used to extract the lenticules. The primary outcome measures were safety and lenticule integrity at the end of the surgery, and the secondary outcome measure was efficacy. Changes in the ocular parameters from the preoperative visit to 1 month postoperative, including uncorrected and corrected distance visual acuity, manifest refraction, lenticule quality, and lenticule residual, were assessed using optical coherence tomography. RESULTS: A total of 246 patients (490 eyes) with myopia and myopic astigmatism were included in the present study. The dissected lenticules ranged in size from 52 to 148 µm. Postoperatively, the lenticule was completely and successfully extracted in all cases. There was no incisional edge tearing during lenticule separation. CONCLUSIONS: Ye's swing technique is a safe and effective procedure for lenticule dissection and refractive outcomes. We have now adopted this technique as our routine method for performing the SMILE procedure.

The efficacy of mindfulness-based stress reduction vs. standard or usual care in patients with breast cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: Mindfulness-based stress reduction (MBSR) has become an alternative intervention for cancer patients, but its impact on depression and quality of life (QOL) of breast cancer patients remains controversial. The aim of this study was to evaluate the effects of MBSR vs. standard or usual care to relieve psychological stress in patients with breast cancer. Methods: According to the PICOS principles, databases [PubMed, Cochrane Database, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (VIP), and Wanfang Database] were searched for randomized controlled trials (RCTs) on the evaluation of MBSR vs. standard or usual care for patients with breast cancer, the outcome variables included depression, stress, anxiety, fatigue, sleep and QOL. Review Manager 5.4 was used to evaluate the effects of the results among selected articles. Forest plots and funnel plots were also performed. The risk of bias was assessed using the Cochrane Risk of Bias Tool. Results: The final analysis included 14 studies with a total of 2,224 patients (1,138 in the MBSR group and 1,086 in the control group). The overall results of risk of bias assessment showed that the reporting bias among articles was high, and other bias was relatively moderate. Funnel plots and Egger's tests showed that there was no significant publication bias. Compared with standard or usual care, MBSR effectively relieved the psychological stress [mean difference (MD), -1.72; 95% confidence interval (CI): (-2.53, -0.92); P<0.0001] and anxiety [standardized mean difference (SMD), -1.36; 95% CI: (-2.13, -0.60); P=0.0005] of breast cancer patients, and improved depression [SMD, -0.62; 95% CI: (-1.20, -0.03); P=0.04] and sleep status [MD, -0.42; 95% CI: (-0.73, -0.10), P=0.009]. However, it had no significant effect on fatigue [SMD, -0.97; 95% CI: (-2.24, 0.31); P=0.14] or QOL [MD, 1.95; 95% CI: (-3.15, 7.05); P=0.45]. Conclusions: MBSR was better than standard or usual care for relieving psychological stress, anxiety, depression, and sleep in patients with breast cancer. Considering the limitations of this article, such as high risk of bias and high heterogeneity of included studies, the interpretation of this conclusion should be cautious.

Comparison of Astigmatic Correction With and Without Cross-axis Alignment During Small Incision Lenticule Extraction.

PURPOSE: To compare clinical outcomes after astigmatism correction via small incision lenticule extraction (SMILE) with and without cross-axis alignment. METHODS: This prospective study included patients who underwent SMILE with astigmatism of greater than 0.75 diopters (D). In the alignment group, head position was readjusted by cross-axis alignment before the standard SMILE procedure. First, the cross-axis was aligned to corresponding green lines on the headrest. Then, the patient's head was adjusted to align the horizontal line to the outer canthus of both eyes and align the vertical line connecting the midpoints of the eyebrows and the bridge of the nose. Changes in ocular parameters were assessed, and vector analysis was performed 6 months postoperatively. RESULTS: The alignment and control groups included 61 and 54 eyes, respectively. Postoperatively, the safety and efficacy indices were comparable between the two groups. Notably, refractive cylinder differed significantly in the alignment group (-0.23 ± 0.26 D) compared to the control group (-0.36 ± 0.26 D) (P = .007). Forty-eight (78.7%) and 32 (59.3%) eyes in the alignment and control groups (P = .03) achieved an angle of error within ±5°, respectively. Vector analysis showed a significantly lower difference vector and a significantly better index of success in the alignment group than that in the control group (0.24 ± 0.25 vs 0.35 ± 0.24, P = .003 and 0.20 ± 0.22 vs 0.29 ± 0.22, P = .02, respectively). Moreover, the change in corneal trefoil differed significantly between the groups (P < .001). CONCLUSIONS: Cross-axis alignment for head positioning in SMILE significantly minimizes axis misalignment and reduces undercorrection astigmatism in myopic astigmatism correction. This technique is a non-invasive and effective method, especially for beginners. [J Refract Surg. 2022;38(10):624-631.].

Role of circular RNAs in disease progression and diagnosis of cancers: An overview of recent advanced insights.

Tumor microenvironment (TME) is a crucial regulator of tumor progression and cells in the TME release a number of molecules that are responsible for anaplasticity, invasion, metastasis of tumor, establishing stem cell niches, up-regulation and down-regulation of various pathways in cancer cells, interfering with immune surveillance and immune escape. Moreover, they can serve as diagnostic markers, and determine effective therapies. Among them, CircRNAs have gained special attention due to their involvement in mutated pathways in cancers. By functioning as a molecular sponge for miRNAs, binding with proteins, and directing selective splicing. CircRNAs modify the immunological environment of cancers to promote their growth. Besides of critical role in tumor growth, circRNAs are emerging as potential candidates as biomarkers for diagnosis cancer therapy. Also, circRNAs vaccination even offers a novel approach to tumor immunotherapy. Over the recent years, studies are advocating that circRNAs have tissue specific tumor specific expression patterns, which indicates their potential clinical utility. Especially, circRNAs have emerged as potential predictive and prognostic biomarkers. Although, there has been significant progress in deciphering the role of circRNA in cancers, literature lacks comprehensive overview on this topic. Keeping in view of these significant discoveries, this review systematically discusses circRNA and their role in the tumor in different dimensions.

The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome Pathways.

Gouty arthritis (GA) is a frequent inflammatory disease characterized by pain, swelling, and stiffness of joints. Neoastilbin is a flavonoid isolated from the rhizome of Smilax glabra, which possesses various anti-inflammatory effects. However, the mechanism of neoastilbin in treating GA has not yet been clarified. Thus, this study was to investigate the protective effects of neoastilbin in both monosodium urate (MSU) stimulated THP-1-derived macrophages and the animal model of GA by injecting MSU into the ankle joints of mice. The levels of key inflammatory cytokines in MSU stimulated THP-1-derived macrophages were detected by enzyme-linked immunosorbent assay (ELISA) kits. Protein expressions of nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome pathways were further detected by Western blotting. In addition, swelling degree of ankle joints, the levels of inflammatory factors, infiltration of inflammatory cells and the expressions of related proteins were determined. Swelling degree and histopathological injury in ankle joints of MSU-injected mice were significantly decreased after being treated with neoastilbin. Moreover, neoastilbin significantly diminished the secretion of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), suppressing the activation of NF-κB and NLRP3 inflammasome pathways in both MSU stimulated THP-1-derived macrophages and the mouse model of GA. In summary, neoastilbin could alleviate GA by inhibiting the NF-κB and NLRP3 inflammasome pathways, which provided some evidence for neoastilbin as a promising therapeutic agent for GA treatment.

Structural characterization of a polysaccharide from Trametes sanguinea Lloyd with immune-enhancing activity via activation of TLR4.

A bioactive polysaccharide (TS2-2A) with a molecular weight of 15 kDa was isolated from Trametes sanguinea Lloyd, a medicinal food homologous fungus, by water extraction-alcohol precipitation and chromatographic separation. NMR analysis of polysaccharide and MS/MS analysis of its oligosaccharide indicated that TS2-2A featured a novel straight chain with a backbone of 1,3-α-d-glucopyranose and 1,4-ß-d-glucopyranose at a molar ratio of 1:4. Moreover, TS2-2A, recognized by Toll-like receptor 4 (TLR4), stimulated RAW 264.7 macrophages to release related cytokines and contributed to immune-enhancing effects. Briefly, with remarkable immune-enhancing activity and noncytotoxicity, TS2-2A was proposed to be a potential immune enhancer for supplementing drugs or functional foods.

Biomimetic Nanoparticles Carrying a Repolarization Agent of Tumor-Associated Macrophages for Remodeling of the Inflammatory Microenvironment Following Photothermal Therapy.

The complete regression of residual tumors after photothermal therapy (PTT) depends on the activation and recognition of the immune system. However, the inevitable local inflammation after PTT in residual tumor recruits abundant abnormal immune cells, especially the tumor-associated macrophages (TAMs) which further promote immune escape and survival of the remaining tumor cells, resulting in the tumor recurrence and progression. To solve this problem, herein we explored biomimetic nanoparticles carrying repolarization agent of TAMs to remodel the post-PTT inflammatory microenvironment. The polydopamine nanoparticles were used simultaneously as photothermal transduction agents to ablate tumor cells and the delivery vehicles for TMP195 which can repolarize the M2-like TAMs into an antitumor phenotype. In addition, a biomimetic decoration of macrophage membrane coating was designed to endow nanoparticles the ability to actively target the tumor site after PTT mediated by inflammation-mediated chemotaxis. In the breast tumor model, these biomimetic nanoparticles with immune-modulating ability significantly elevated the levels of M1-like TAMs, ultimately resulting in a tumor-elimination rate of 60%, increased from 10% after PTT. This synergistic treatment strategy of PTT and TAMs repolarization provides a promising approach to address the deteriorated tumor microenvironment after PTT and proposes a more effective way for combinational treatment option in clinic.

On-Chip Construction of Liver Lobules with Self-Assembled Perfusable Hepatic Sinusoid Networks.

Although various liver chips have been developed using emerging organ-on-a-chip techniques, it remains an enormous challenge to replicate the liver lobules with self-assembled perfusable hepatic sinusoid networks. Herein we develop a lifelike bionic liver lobule chip (LLC), on which the perfusable hepatic sinusoid networks are achieved using a microflow-guided angiogenesis methodology; additionally, during and after self-assembly, oxygen concentration is regulated to mimic physiologically dissolved levels supplied by actual hepatic arterioles and venules. This liver lobule design thereby produces more bionic liver microstructures, higher metabolic abilities, and longer lasting hepatocyte function than other liver-on-a-chip techniques that are able to deliver. We found that the flow through the unique micropillar design in the cell coculture zone guides the radiating assembly of the hepatic sinusoid, the oxygen concentration affects the morphology of the sinusoid by proliferation, and the oxygen gradient plays a key role in prolonging hepatocyte function. The expected breadth of applications our LLC is suited to is demonstrated by means of preliminarily testing chronic and acute hepatotoxicity of drugs and replicating growth of tumors in situ. This work provides new insights into designing more extensive bionic vascularized liver chips, while achieving longer lasting ex-vivo hepatocyte function.

An iron oxide nanoparticle-based transdermal nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors.

Transdermal delivery is an attractive strategy for treating superficial tumors. However, the applications of existing transdermal systems have been limited by low transdermal efficiency and poor therapeutic outcomes. Here, we develop a transdermal nanoplatform (+)T-SiDs, based on superparamagnetic iron oxide core, surface-modified with cationic lipids, transdermal enhanced peptide TD, and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR), and loaded with doxorubicin. The (+)T-SiDs compositions enable MR/NIR dual-modal imaging guided synergistic chemo-photothermal therapy to superficial tumors treatment via transdermal delivery. The (+)T-SiDs exhibit good stability, efficient cellular uptake, pH/photothermal responsive drug release, and high photothermal conversion efficiency (47.45%). Importantly, the transdermal delivery of (+)T-SiDs is significantly enhanced by TD functionalization. In vivo MR/NIR imaging shows that the (+)T-SiDs exhibit high transdermal efficiency and specificity in localization to the tumor site. Moreover, in comparison with individual chemo- or photothermal therapies, the combination of chemo-photothermal therapy exhibits more efficient tumor inhibition effects. This work presents a new transdermal treatment nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors, with efficient tumor eradication and low systemic toxicity thus offering strong potential for clinical adoption. STATEMENT OF SIGNIFICANCE: Transdermal delivery is an attractive strategy for treating superficial tumors. However, a highly efficient transdermal nanoplatform remains to be developed. Herein, we designed a multifunctional transdermal nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors, comprised of a super-paramagnetic iron oxide (SPIO) nanoparticle, which can act as an MRI contrast agent and photothermal agent; a transdermal enhanced peptide (TD) and cationic lipids, which can accelerate skin penetration; and a NIR dye (DiR) and doxorubicin (DOX), which can achieve a synergistic enhanced chemo-photothermal therapy with NIR imaging ability. The transdermal nanoplatform achieved efficient tumor eradication and low systemic toxicity, thus offering strong potential for clinical adoption.

Enhanced transdermal efficiency of curcumin-loaded peptide-modified liposomes for highly effective antipsoriatic therapy.

Psoriasis is one of the most influential and fastest-growing inflammatory diseases of the skin. Curcumin (CRC) is an effective antipsoriatic drug that is often carried by nanoparticles or liposomes mainly administered via the skin. However, the therapeutic effectiveness and bioavailability of this drug are restricted due to the functions of the skin barrier to liposomes. Herein, we proposed a peptide-modified curcumin-loaded liposome (CRC-TD-Lip) to expedite the transdermal delivery of curcumin and enhance the inhibition of psoriasis. CRC-TD-Lip was prepared and dispersed uniformly with high stability and high curcumin encapsulation efficiency. We confirmed the improved intracellular uptake of CRC-TD-Lip, the increased inhibitory effect of CRC-TD-Lip on HaCaT cells, and the heightened transdermal ability of CRC-TD-Lip. Then, the enhanced antipsoriatic ability of CRC-TD-Lip was evaluated in vivo using an imiquimod-induced psoriasis mouse model. The results indicated that the developed CRC-TD-Lip can effectively improve the delivery of curcumin across the skin and enhance the antipsoriasis efficiency. This work can provide a strategy for enhancing the transdermal delivery efficiency of drugs for various skin diseases.