Quantitative assessment of hyperperfusion using arterial spin labeling to predict hemorrhagic transformation in acute ischemic stroke patients with mechanical endovascular therapy.

OBJECTIVES: This study was aimed to quantitatively assess hyperperfusion using arterial spin labeling (ASL) to predict hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients. METHODS: This study enrolled 98 AIS patients with anterior circulation large vessel occlusion within 24 h of symptom onset. ASL was performed before mechanical endovascular therapy. On pre-treatment ASL maps, a region with relative cerebral blood flow (CBF) ≥ 1.4 was defined as an area of hyperperfusion. The maximum CBF (CBFmax) of hyperperfusion was calculated for each patient. A non-contrast CT scan was performed during the subacute phase for the evaluation of HT. Good clinical outcome was defined as a 90-day modified Rankin scale score of 0-2. RESULTS: The CBFmax of hyperperfusion (odds ratio, 1.023; 95% confidence interval [CI], 1.005-1.042; p = 0.012) was an independent risk factor for the status of HT. The CBFmax of hyperperfusion for HT showed an area under the curve of 0.735 (95% CI, 0.588-0.882) with optimal cutoff value, sensitivity, and specificity being 146.5 mL/100 g/min, 76.9%, and 69.6%, respectively. There was a statistically significant relationship between HT grades (from no HT to PH2) and CBFmax of hyperperfusion with a Spearman rank correlation of 0.446 (p = 0.001). In addition, low CBFmax of hyperperfusion were associated with good functional outcome (95% CI, 17.130-73.910; p = 0.002). CONCLUSIONS: High CBFmax of hyperperfusion was independently associated with subsequent HT and low CBFmax of hyperperfusion linked to good functional outcome. There was a positive correlation between HT grade and CBFmax. CLINICAL RELEVANCE STATEMENT: Arterial spin labeling is a noninvasive and contrast agent-independent technique, which is sensitive in detecting hyperperfusion. This study shows that the cerebral blood flow of hyperperfusion is associated with clinical prognosis, which will benefit more patients. KEY POINTS: • Quantitative assessment of hyperperfusion using pre-treatment arterial spin labeling to predict hemorrhagic transformation and prognosis in acute ischemic stroke patients. • The maximum cerebral blood flow of hyperperfusion was associated with hemorrhagic transformation and clinical prognosis and higher maximum cerebral blood flow of hyperperfusion was associated with higher grade hemorrhagic transformation. • The maximum cerebral blood flow of hyperperfusion can predict hemorrhagic transformation which enables timely intervention to prevent parenchymal hematoma.

Multi-Parametric MRI for Evaluating Variations in Renal Structure, Function, and Endogenous Metabolites in an Animal Model With Acute Kidney Injury Induced by Ischemia Reperfusion.

BACKGROUND: Ischemia reperfusion injury (IRI)-induced acute kidney injury (AKI) may occur after renal ischemic injury. There is a lack of an accurate and comprehensive detection technique for IRI-AKI. PURPOSE: To longitudinally evaluate IRI-AKI in rats by renal structure, function, and metabolites using multi-parametric MRI (mpMRI). STUDY TYPE: Prospective. ANIMAL MODEL: Forty-eight rats undergoing IRI-AKI. FIELD STRENGTH/SEQUENCE: 7-T, T1 mapping, and arterial spin labeling (ASL): echo planar imaging (EPI) sequence; blood oxygen level-dependent (BOLD): gradient recalled echo (GRE) sequence; T2 mapping, quantitative magnetization transfer (qMT), and chemical exchange saturation transfer (CEST): rapid acquisition with relaxation enhancement (RARE) sequence. ASSESSMENT: The mpMRI for IRI-AKI was conducted at 0 (control), 1, 3, 7, 14, and 28 days, all included eight rats. The longitudinal mpMRI signal of manually outlined cortex, outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla, and medulla plus pelvis were calculated and compared, their diagnosis performance for IRI-AKI also been evaluated. STATISTICAL TESTS: Pearson correlations analysis for correlation between mpMRI signal and renal injury, unpaired t-tests for comparing the signal changes, and receiver operating characteristics (ROC) analysis was used to identify most sensitive indicator of mpMRI. A P-value <0.05 was considered statistically significant. RESULTS: Compared with control kidneys, the T1 and T2 values of the cortex and medulla in IRI kidneys increased and reached their highest values on day 14, and the kidneys also showed the most severe edema and segments blurred. The RBF in the cortex and OSOM showed a significant decline after day 3. The BOLD signal in the OSOM largest increased on day 28. The cortical PSR and the amine-CEST both decreased with IRI-AKI progression, and amine-CEST achieved the highest AUC for the diagnosis (0.899). DATA CONCLUSION: Multi-parametric MRI may show comprehensive variations in IRI-AKI, and amine-CEST may exhibit the highest accuracy for diagnosis of IRI-AKI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Indole Diterpenes from Mangrove Sediment-Derived Fungus Penicillium sp. UJNMF0740 Protect PC12 Cells against 6-OHDA-Induced Neurotoxicity via Regulating the PI3K/Akt Pathway.

In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data. The antibacterial and neuroprotective effects of these isolates were examined, and only compounds 6 and 9 exhibited weak antibacterial activity, while compounds 5, 8, and 10 showed protective effects against the injury of PC12 cells induced by 6-hydroxydopamine (6-OHDA). Additionally, compound 5 could suppress the apoptosis and production of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells as well as trigger the phosphorylation of PI3K and Akt. Taken together, our work enriches the structural diversity of indole diterpenes and hints that compounds of this skeleton can repress the 6-OHDA-induced apoptosis of PC12 cells via regulating the PI3K/Akt signaling pathway, which provides evidence for the future utilization of this fascinating class of molecules as potential neuroprotective agents.

Oxygen Vacancy-Laden Confinement Impact on Degradation of Metal Complexes.

Oxygen vacancies (Vo) have been recognized as the superior active site for PS-mediated environmental remediation; however, the formation and activation of Vo associated with the effects of chemical and spatial environments remain ambiguous. Herein, attributing to the low defect-formation energy of Vo in the presence of sulfonate groups, an in situ nucleating Vo-laden CuO nanosheet was deliberately fabricated inside the phase of a sulfonated mesoporous polystyrene substrate (Vo-CuO@SPM). The as-prepared nanocomposite demonstrated an excellent treatment efficiency toward metal complexes [Cu-EDTA as a case] with ignorable Cu(II) leaching, and it can be repeatedly employed for 25 recycles (not limited). Mechanistically, the electron transfer and the mass transport for PDS nonradical activation were proved to be substantially enhanced by the delocalized electrons and with the assistance of the microchannel environment. This work not only establishes insight into the formation of oxygen vacancies but also reveals the PS activation mechanism in the spatially confined sites.

A Paramagnetic Metal-Organic Framework Enhances Mild Magnetic Hyperthermia Therapy by Downregulating Heat Shock Proteins and Promoting Ferroptosis via Aggravation of Two-Way Regulated Redox Dyshomeostasis.

Mild magnetic hyperthermia therapy (MMHT) holds great potential in treating deep-seated tumors, but its efficacy is impaired by the upregulation of heat shock proteins (HSPs) during the treatment process. Herein, Lac-FcMOF, a lactose derivative (Lac-NH2 ) modified paramagnetic metal-organic framework (FcMOF) with magnetic hyperthermia property and thermal stability, has been developed to enhance MMHT therapeutic efficacy. In vitro studies showed that Lac-FcMOF aggravates two-way regulated redox dyshomeostasis (RDH) via magnetothermal-accelerated ferricenium ions-mediated consumption of glutathione and ferrocene-catalyzed generation of ∙OH to induce oxidative damage and inhibit heat shock protein 70 (HSP70) synthesis, thus significantly enhancing the anti-cancer efficacy of MMHT. Aggravated RDH promotes glutathione peroxidase 4 inactivation and lipid peroxidation to promote ferroptosis, which further synergizes with MMHT. H22-tumor-bearing mice treated with Lac-FcMOF under alternating magnetic field (AMF) demonstrated a 90.4% inhibition of tumor growth. This work therefore provides a new strategy for the simple construction of a magnetic hyperthermia agent that enables efficient MMHT by downregulating HSPs and promoting ferroptosis through the aggravation of two-way regulated RDH.

Mn(iii)-mediated carbon-centered radicals generate an enhanced immunotherapeutic effect.

A strategy for designing cancer therapeutic nanovaccines based on immunogenic cell death (ICD)-inducing therapeutic modalities is particularly attractive for optimal therapeutic efficacy. In this work, a highly effective cancer therapeutic nanovaccine (denoted as MPL@ICC) based on immunogenic photodynamic therapy (PDT) was rationally designed and fabricated. MPL@ICC was composed of a nanovehicle of MnO2 modified with a host-guest complex using amino pillar[6]arene and lactose-pyridine, a prodrug of isoniazid (INH), and chlorine e6 (Ce6). The nanovaccine exhibited excellent biosafety, good targeting ability to hepatoma cells and enrichment at tumor sites. Most importantly, it could modulate the tumor microenvironment (TME) to facilitate the existence of Mn(iii) and Mn(iii)-mediated carbon-centered radical generation with INH released from the prodrug in situ to further strengthen ICD. This is the first report on Mn(iii)-mediated generation of carbon-centered radicals for successful anti-tumor immunotherapy using ICD, which provides a novel strategy for designing highly efficient cancer therapeutic nanovaccines.

Defect Engineering and Emission Tuning of Wide-Bandgap MAPbCl3 Perovskite.

Lead-chloride perovskites are promising candidates for optoelectronic applications, such as visible-blind UV photodetection. It remains unclear how the deep defects in this wide-bandgap material impact the carrier recombination dynamics. In this work, we study the defect properties of MAPbCl3 (MA = CH3NH3) based on photoluminescence (PL) measurements. Our investigations show that apart from the intrinsic emission, four sub-bandgap emissions emerge, which are very likely to originate from the radiative recombination of excitons bound to several intrinsic vacancy and interstitial defects. The intensity of various emission features can be tuned by adjusting the type and ratio of precursors used during synthesis. Our study not only provides important insights into the defect property and carrier recombination mechanism in this class of material but also demonstrates efficient strategies for defect passivation and engineering, paving the way for further development of lead-chloride perovskite-based optoelectronic devices.

Assessment of rhabdomyolysis-induced acute kidney injury with chemical exchange saturation transfer magnetic resonance imaging.

Background: Rhabdomyolysis (RM)-induced acute kidney injury (AKI) is a common renal disease with low survival rate and inadequate prognosis. In this study, we investigate the feasibility of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) for assessing the progression of RM-induced AKI in a mouse model. Methods: AKI was induced in C57BL/6J mice via intramuscular injection of 7.5 mL/kg glycerol (n=30). Subsequently, serum creatinine (SCr), blood urea nitrogen (BUN), and hematoxylin-eosin (HE) and Masson staining, were performed. Longitudinal CEST-MRI was conducted on days 1, 3, 7, 15, and 30 after AKI induction using a 7.0-T MRI system. CEST-MRI quantification parameters including magnetization transfer ratio (MTR), MTR asymmetric analysis (MTRasym), apparent amide proton transfer (APT*), and apparent relayed nuclear Overhauser effect (rNOE*) were used to investigate the feasibility of detecting RM-induced renal damage. Results: Significant increases of SCr and BUN demonstrated established AKI. The HE staining revealed various degrees of tubular damage, and Masson staining indicted an increase in the degree of fibrosis in the injured kidneys. Among CEST parameters, the cortical MTR presented a significant difference, and it also showed the best diagnostic performance for AKI [area under the receiver operating characteristic curve (AUC) =0.915] and moderate negative correlations with SCr and BUN. On the first day of renal damage, MTR was significantly reduced in cortex (22.7%±0.04%, P=0.013), outer stripe of outer medulla (24.7%±1.6%, P<0.001), and inner stripe of outer medulla (27.0%±1.5%, P<0.001) compared to the control group. Longitudinally, MTR increased steadily with AKI progression. Conclusions: The MTR obtained from CEST-MRI is sensitive to the pathological changes in RM-induced AKI, indicating its potential clinical utility for the assessment of kidney diseases.

Kartogenin (KGN)/synthetic melanin nanoparticles (SMNP) loaded theranostic hydrogel scaffold system for multiparametric magnetic resonance imaging guided cartilage regeneration.

Cartilage regeneration after injury is still a great challenge in clinics, which suffers from its avascularity and poor proliferative ability. Herein we designed a novel biocompatible cellulose nanocrystal/GelMA (gelatin-methacrylate anhydride)/HAMA (hyaluronic acid-methacrylate anhydride)-blended hydrogel scaffold system, loaded with synthetic melanin nanoparticles (SMNP) and a bioactive drug kartogenin (KGN) for theranostic purpose. We found that the SMNP-KGN/Gel showed favorable mechanical property, thermal stability, and distinct magnetic resonance imaging (MRI) contrast enhancement. Meanwhile, the sustained release of KGN could recruit bone-derived mesenchymal stem cells to proliferate and differentiate into chondrocytes, which promoted cartilage regeneration in vitro and in vivo. The hydrogel degradation and cartilage restoration were simultaneously monitored by multiparametric MRI for 12 weeks, and further confirmed by histological analysis. Together, these results validated the multifunctional hydrogel as a promising tissue engineering platform for noninvasive imaging-guided precision therapy in cartilage regenerative medicine.

Nitrogen and phosphorous dynamics with stand development of Pinus massoniana plantations in Southeast China.

Introduction: Nutrient resorption is a key mechanism to conserve nutrients and overcome nutrient limitation in perennial plants. As an important afforested tree species in subtropical regions, Pinus massoniana grows well in nutrient-poor environments, however, the age-related pattern of nutrient acquisition strategy and the underlying mechanisms in P. massoniana plantations remain unclear. Methods: In this study, concentrations of nitrogen (N) and phosphorus (P) were measured in green and senesced needles, roots and soil samples collected from P. massoniana plantations with different stand ages (9-, 17-, 26-, 34- and 43-year-old) in south China. From these samples, nutrient resorption efficiency (RE) and stoichiometry were calculated. Results: Needle PRE significantly decreased with stand age, while there was no clear pattern of NRE along the stand development. Green needle N:P in older stands was significantly lower than in younger ones. Senesced needle C:P and N:P significantly decreased with stand age. Root and soil available P concentrations were significantly higher in older stands than in younger ones, and PRE was negatively correlated with soil available P concentration. Discussion: There was a shift from "conservative consumption" to "resource spending" P-use strategy, and P limitation decreased with stand development of P. massoniana plantations. The results provide information of changes in nutrients dynamics, which is relevant for the sustainable management of subtropical forest plantations.

A hyaluronic acid modified cuprous metal-organic complex for reversing multidrug resistance via redox dyshomeostasis.

Multidrug resistance (MDR) which is often related to the overexpression of P-glycoprotein (P-gp) in drug-resistant cancer cells has been a major problem faced by current cancer chemotherapy. Reversing P-gp-related MDR by disrupting tumor redox homeostasis that regulates the expression of P-gp is a promising strategy. In this work, a hyaluronic acid (HA) modified nanoscale cuprous metal-organic complex (HA-CuTT) was developed to reverse P-gp-related MDR via two-way regulated redox dyshomeostasis, which was achieved by both Cu+-catalyzed generation of •OH and disulfide bonds-mediated depletion of glutathione (GSH). In vitro studies reveal that the DOX-loaded complex (HA-CuTT@DOX) has excellent targeting ability to HepG2-ADR cells due to the modification of HA and effectively induces redox dyshomeostasis in HepG2-ADR cells. Moreover, HA-CuTT@DOX can cause mitochondrial damage, decrease ATP level, and downregulate the P-gp expression, thereby leading to the reversal of MDR and the increased drug accumulation in HepG2-ADR cells. Importantly, in vivo experimental results show that it can achieve effective inhibition (89.6 %) of tumor growth in nude mice bearing HepG2-ADR cells. This is the first work to reverse P-gp-related MDR via two-way regulated redox dyshomeostasis based on a HA modified nanoscale cuprous metal-organic complex, providing a new therapeutic paradigm for effective treatment of MDR-related cancer.

Prognostic factors affecting the ruptured intracranial aneurysms: A 9-year multicenter study in Fujian, China.

BACKGROUND: A multicenter retrospective study was conducted to explore the factors affecting short-term prognosis and long-term outcomes of intracranial aneurysms (IA) rupture. Further, the prognosis prediction model was constructed based on survival analysis, contributing to the development of prevention strategies for aneurysmal subarachnoid hemorrhage. METHODS: Data of 1280 patients with IA rupture were gathered between 2014 and 2022 in Fujian, China. Logistic regression was implemented to study the short-term prognostic factors of IA rupture. Survival analysis of 911 patients among them was performed to explore the long-term outcome status by Cox risk assessment. Nomogram prognosis models were constructed using R software. RESULTS: The findings displayed that blood type O (OR = 1.79; P = 0.019), high systolic pressure (OR = 1.01; P < 0.001), Glasgow Coma score (GCS) 9-12 (OR = 2.73; P = 0.022), GCS < 9 (OR = 3.222; P = 0.006), diabetes (OR = 2.044; P = 0.040), and high white blood cell count (OR = 1.059, P = 0.040) were core influencing factors for poor short-term prognosis. Survival analysis revealed that age > 60 years (HR = 2.87; P = 0.001), hypertension (HR = 1.95; P = 0.001), conservative (HR = 6.89; P < 0.001) and endovascular treatment (HR = 2.20; P = 0.001), multiple ruptured IAs (HR = 2.37; P = 0.01), Fisher 3 (HR = 1.68; P = 0.09), Fisher 4 (HR = 2.75; P = 0.001), and Hunt-Hess 3 (HR = 0.55; P = 0.05) were the major risk factors for terrible long-term outcomes. CONCLUSIONS: People over 60 years with characteristics of type O blood, high systolic pressure, diabetes, high white blood cell count, and onset GCS < 12 will have more complications and a worse short-term prognosis. Those aged > 60 years with hypertension, conservative and endovascular treatment, multiple ruptured IAs, Fisher ≥ 3 and Hunt-Hess 3 have a greater risk of poor long-term prognosis.

Ratiometric chemical exchange saturation transfer pH mapping using two iodinated agents with nonequivalent amide protons and a single low saturation power.

Background: As an essential physiological parameter, pH plays a critical role in maintaining cellular and tissue homeostasis. The ratiometric chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) method using clinically approved iodinated agents has emerged as one of the most promising noninvasive techniques for pH assessment. Methods: In this study, we investigated the ability to use the combination of two different nonequivalent amide protons, chosen from five iodinated agents, namely iodixanol, iohexol, iobitridol, iopamidol, and iopromide, for pH measurement. The ratio of two nonequivalent amide CEST signals was calculated and compared for pH measurements in the range of 5.6 to 7.6. To quantify the CEST signals at 4.3 and 5.5 parts per million (ppm), we employed two analytic methods: magnetization transfer ratio asymmetry and Lorentzian fitting analysis. Lastly, the established protocol was used to measure the pH values in healthy rat kidneys (n=5). Results: The combination of iodixanol and iobitridol at a ratio of 1:1 was found to be suitable for pH mapping. The saturation power level (B1) was also investigated, and a low B1 of 1.5 µT was adopted for subsequent pH measurements. Improved precision and an extended pH detection range were achieved using iodixanol and iobitridol (1:1 ratio) and a single low B1 of 1.5 µT in vitro. In vivo renal pH values were measured as 7.23±0.09, 6.55±0.15, and 6.29±0.23 for the cortex, medulla, and calyx, respectively. Conclusions: These results show that the ratiometric CEST method using two iodinated agents with nonequivalent amide protons could be used for in vivo pH mapping of the kidney under a single low B1 saturation power.

The Emerging Roles of Human Gut Microbiota in Gastrointestinal Cancer.

The gut microbiota is composed of a large number of microorganisms with a complex structure. It participates in the decomposition, digestion, and absorption of nutrients; promotes the development of the immune system; inhibits the colonization of pathogens; and thus modulates human health. In particular, the relationship between gut microbiota and gastrointestinal tumor progression has attracted widespread concern. It was found that the gut microbiota can influence gastrointestinal tumor progression in independent ways. Here, we focused on the distribution of gut microbiota in gastrointestinal tumors and further elaborated on the impact of gut microbiota metabolites, especially short-chain fatty acids, on colorectal cancer progression. Additionally, the effects of gut microbiota on gastrointestinal tumor therapy are outlined. Finally, we put forward the possible problems in gut microbiota and the gastrointestinal oncology field and the efforts we need to make.

A GLUTs/GSH cascade targeting-responsive bioprobe for the detection of circulating tumor cells.

A GLUTs/GSH cascade targeting-responsive bioprobe, GluCC, was rationally designed and synthesized for the first time via the coordination of copper ions with a glucose-modified coumarin derivative ligand (GluC). GluCC can specifically detect circulating tumor cells (CTCs) in lung metastatic mice models by targeting the Warburg effect and responding to overexpressed glutathione in the tumor microenvironment. This bioprobe with a simple detection procedure has significant advantages for CTC detection.

Current treatments for non-small cell lung cancer.

Despite improved methods of diagnosis and the development of different treatments, mortality from lung cancer remains surprisingly high. Non-small cell lung cancer (NSCLC) accounts for the large majority of lung cancer cases. Therefore, it is important to review current methods of diagnosis and treatments of NSCLC in the clinic and preclinic. In this review, we describe, as a guide for clinicians, current diagnostic methods and therapies (such as chemotherapy, chemoradiotherapy, targeted therapy, antiangiogenic therapy, immunotherapy, and combination therapy) for NSCLC.

[Soil Enzyme Stoichiometric Characteristics of Pinus massoniana Plantations at Different Stand Ages in Mid-subtropical Areas].

Soil enzyme activity is an important index to characterize the nutrient requirements and nutrient limitations of soil microorganisms. In this study, Pinus massoniana plantations of different stand ages (9, 17, 26, 34, and 43 a) in mid-subtropical China were taken as the research object; the activities of ß-glucosidase (BG), N-acetyl-ß-glucosaminidase (NAG), leucine amino-peptidase (LAP), acid phosphatase (AP), polyphenol oxidase (POX), and peroxidase (POD) were determined; and soil enzyme stoichiometric ratios were also calculated to investigate the soil microbial nutrient limitations of P. massoniana plantation development. The results showed that the activities of BG, NAG, AP, POX, and POD were enhanced with the increase in stand age, and the activity of LAP was the lowest at 17 a, which showed a significant difference and fluctuated among the neighboring stand ages. The soil enzyme C:N:P stoichiometric ratio was 1:1:0.56, which deviated from the global ecosystem enzyme C:N:P stoichiometric ratio (1:1:1). The enzyme C:N increased, whereas the enzyme N:P decreased, with increasing stand age, and both ratios tended to be stable after 17 a. There was no significant difference in enzyme N:P among different stand ages. The vector length of enzyme stoichiometry was not significantly different among the five stand ages. The vector angles increased with the increase in stand ages and tended to be stable after 17 a of stand age, but the angles were less than 45°. Redundancy analysis (RDA) revealed that soil carbon quality index and pH were the main factors influencing soil enzyme activity and the associated stoichiometric ratio. Our findings indicated that P. massoniana plantation soil microorganisms at different growth stages were all subjected to N limitation, and the N limitation was alleviated with the increase in stand age; however, the P requirement was gradually enhanced. Therefore, the management of P. massoniana plantations should take care to increase nitrogen fertilizer at the early growth stage of P. massoniana, and more phosphorus fertilizers need to be applied with nitrogen at the late growth stage in order to maintain the productivity and sustainable development of P. massoniana plantations.

A disulfide-induced supra-amphiphilic co-assembly for glycosylated pro-drug-photosensitizer nanoparticles in combination therapies.

A disulfide-induced supra-amphiphilic co-assembly strategy for hydrophobic drug co-delivery in combination therapies was proposed based on a disulfide bond containing hydrophobic pro-drug-photosensitizer (BG) and a hydrophilic/targeting dimer lactose molecule (Lac-SS-Lac). The anti-tumor efficiency was significantly enhanced by the combination therapies of epidermal growth factor receptor (EGFR) targeted therapy and phototherapy in EGFR-positive and/or galectin overexpressed tumors.

Nanococktail Based on Supramolecular Glyco-Assembly for Eradicating Tumors In Vivo.

The development of robust phototherapeutic strategies for eradicating tumors remains a significant challenge in the transfer of cancer phototherapy to clinical practice. Here, a phototherapeutic nanococktail atovaquone/17-dimethylaminoethylamino-17-demethoxygeldanamycin/glyco-BODIPY (ADB) was developed to enhance photodynamic therapy (PDT) and photothermal therapy (PTT) via alleviation of hypoxia and thermal resistance that was constructed using supramolecular self-assembly of glyco-BODIPY (BODIPY-SS-LAC, BSL-1), hypoxia reliever atovaquone (ATO), and heat shock protein inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG). Benefiting from a glyco-targeting and glutathione (GSH) responsive units BSL-1, ADB can be rapidly taken up by hepatoma cells, furthermore the loaded ATO and 17-DMAG can be released in original form into the cytoplasm. Using in vitro and in vivo results, it was confirmed that ADB enhanced the synergetic PDT and PTT upon irradiation using 685 nm near-infrared light (NIR) under a hypoxic tumor microenvironment where ATO can reduce O2 consumption and 17-DMAG can down-regulate HSP90. Moreover, ADB exhibited good biosafety, and tumor eradication in vivo. Hence, this as-developed phototherapeutic nanococktail overcomes the substantial obstacles encountered by phototherapy in tumor treatment and offers a promising approach for the eradication of tumors.

Application Perspectives of Nanomedicine in Cancer Treatment.

Cancer is a disease that seriously threatens human health. Based on the improvement of traditional treatment methods and the development of new treatment modes, the pattern of cancer treatment is constantly being optimized. Nanomedicine plays an important role in these evolving tumor treatment modalities. In this article, we outline the applications of nanomedicine in three important tumor-related fields: chemotherapy, gene therapy, and immunotherapy. According to the current common problems, such as poor targeting of first-line chemotherapy drugs, easy destruction of nucleic acid drugs, and common immune-related adverse events in immunotherapy, we discuss how nanomedicine can be combined with these treatment modalities, provide typical examples, and summarize the advantages brought by the application of nanomedicine.