A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5ß1-targeted gold nanorods.

BACKGROUND: Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. RESULTS: In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5ß1 integrin expressed by bladder cancer cells. This product (called GNRs@PEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5ß1 and α5ß1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5ß1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5ß1-negative), pointing to a specific targeting mechanism. CONCLUSION: GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions.

The relationship between cognitive reserve and the spontaneous use of emotion regulation strategies in older adults: a cross-sectional study.

BACKGROUND: Several studies reported cognitive reserve (CR) as an important factor in promoting healthy aging within a non-clinical aging population. AIMS: The main goal of the present study is to investigate the link between higher levels of CR and more effective emotion regulation. In more detail, we examine the association between a number of CR proxies and the habitual use of two emotion regulation strategies, cognitive reappraisal and emotional suppression. METHODS: Three hundred and ten older adults aged between 60 and 75 (mean = 64.45, SD = 4.37; 69.4% female) joined this cross-sectional study by filling out self-report measures of CR and emotion regulation.² RESULTS: Reappraisal and suppression use were correlated. Practicing different leisure activities constantly over many years, being more original and having a higher education promoted more frequent use of cognitive reappraisal. These CR proxies were also significantly related to suppression use, even though the percentage of variance explained was lower. DISCUSSION AND CONCLUSIONS: Exploring the role played by the cognitive reserve on different emotion regulation techniques can be useful in understanding which variables predict the use of antecedent-focused (reappraisal) or response-focused (suppression) emotion regulation strategies in aging individuals.

Exploring Patients' Trust from a New Perspective. A Text-Analysis Study.

The concept of trust has been extensively studied within the field of medicine. Yet, a list of factors that clearly influence patients' trust is still under debate. Moreover, the methodological approaches found in literature have been reported to be lacking in their assessments and measurements of trust relationships in the medical field although trust between a patient and medical provider has been proven to increase adherence and improve health outcomes. Hence, adding data to this debate and exploring a reliable method to explore the construct of trust is relevant. This study collects new evidence of the most salient indicators of patient trust by using a narrative approach and highlighting the potential of this method in collecting indicators that could be used to build training that aims to increase patients' trust. We used the Linguistic Inquiry and Word Count software for text analysis to examine the spontaneous narrations of episodes of trust and distrust within the doctor-patient relationship with a sample of 82 adult patients. Results demonstrate the role of the emotional aspects of the doctor-patient relationship. Data highlights the importance of doctors' benevolence toward patients, and positive emotions seem to be deeply connected with any experience of trust, which leads patients to feel more secure. Methods are presented to use these insights to construct mechanisms that establish medical trust and allow providers to implement effective interventions.

Challenge your Brain. Blogging during the COVID Lockdown as a Way to Enhance Well-Being and Cognitive Reserve in an Older Population.

BACKGROUND: The lockdown linked with COVID-19 restrictions has been reported to have severe consequences at an emotional and cognitive level, this was especially true for vulnerable populations, such as the older adults. This study aims at exploring the effect of a blog-based intervention implemented during COVID lockdown to increase the perceived well-being and cognitive reserve (CR) of a sample of American older adults. METHODS: Forty-one participants (63% female), age range from 64 to 83, participated in a blog-based 5-week intervention. Their level of well-being as well as cognitive reserve were assessed before and after the intervention with specific scales. Participants were matched by age, gender and education level to a quasi-equivalent control group living in the same area who was tested on the same variables. RESULTS: Results showed a significant increase in both perceived well-being and CR in the intervention group. A significant difference was also found when comparing the intervention group to the matched controls.

Enhancement of doxorubicin anti-cancer activity by vascular targeting using IsoDGR/cytokine-coated nanogold.

BACKGROUND: Gold nanospheres tagged with peptides containing isoDGR (isoAsp-Gly-Arg), an αvß3 integrin binding motif, represent efficient carriers for delivering pro-inflammatory cytokines to the tumor vasculature. We prepared bi- or trifunctional nanoparticles bearing tumor necrosis factor-α (TNF) and/or interleukin-12 (IL12) plus a peptide containing isoDGR, and we tested their anti-cancer effects, alone or in combination with doxorubicin, in tumor-bearing mice. RESULTS: In vitro biochemical studies showed that both nanodrugs were monodispersed and functional in terms of binding to TNF and IL12 receptors and to αvß3. In vivo studies performed in a murine model of fibrosarcoma showed that low doses of bifunctional nanoparticles bearing isoDGR and TNF (corresponding to few nanoparticles per cell) delayed tumor growth and increased the efficacy of doxorubicin without worsening its toxicity. Similar effects were obtained using trifunctional nanoparticles loaded with isoDGR, TNF and IL12. Mechanistic studies showed that nanoparticles bearing isoDGR and TNF could increase doxorubicin penetration in tumors a few hours after injection and caused vascular damage at later time points. CONCLUSION: IsoDGR-coated gold nanospheres can be exploited as a versatile platform for single- or multi-cytokine delivery to cells of the tumor vasculature. Extremely low doses of isoDGR-coated nanodrugs functionalized with TNF or TNF plus IL12 can enhance doxorubicin anti-tumor activity.

Topical Administration of 15-Deoxy-Δ 12,14-Prostaglandin J2 Using a Nonionic Cream: Effect on UVB-Induced Skin Oxidative, Inflammatory, and Histopathological Modifications in Mice.

UVB radiation is certainly one of the most important environmental threats to which we are subjected to. This fact highlights the crucial protective role of the skin. However, the skin itself may not be capable of protecting against UVB depending on irradiation intensity and time of exposition. Sun blockers are used to protect our skin, but they fail to fully protect it against oxidative and inflammatory injuries initiated by UVB. To solve this issue, topical administration of active molecules is an option. 15-Deoxy-Δ 12,14-prostaglandin J2 (15d-PGJ2) is an arachidonic acid-derived lipid with proresolution and anti-inflammatory actions. However, as far as we are aware, there is no evidence of its therapeutic use in a topical formulation to treat the deleterious events initiated by UVB, which was the aim of the present study. We used a nonionic cream to vehiculate 15d-PGJ2 (30, 90, and 300 ng/mouse) (TFcPGJ2) in the skin of hairless mice. UVB increased skin edema, myeloperoxidase activity, metalloproteinase-9 activity, lipid peroxidation, superoxide anion production, gp91phox and COX-2 mRNA expression, cytokine production, sunburn and mast cells, thickening of the epidermis, and collagen degradation. UVB also diminished skin ability to reduce iron and scavenge free radicals, reduced glutathione (GSH), sulfhydryl proteins, and catalase activity. TFcPGJ2 inhibited all these pathological alterations in the skin caused by UVB. No activity was observed with the unloaded topical formulation. The protective outcome of TFcPGJ2 indicates it is a promising therapeutic approach against cutaneous inflammatory and oxidative pathological alterations.

Effects of short- and long-term neurostimulation (tDCS) on Alzheimer's disease patients: two randomized studies.

BACKGROUND: Non-invasive brain stimulation is an effective treatment for Alzheimer's disease. AIMS: The purpose of the two studies presented here is to compare the short- and long-term effects of transcranial direct current stimulation (t-DCS) on two samples of advanced AD patients. METHODS: In Study 1 26 patients were involved in a 10-day anodal vs. sham tDCS intervention stimulating the left frontotemporal cortex. A pre-post test assessment was run using two different neurocognitive tests and EEG data. The same protocol was used in Study 2, which involved 18 different patients who underwent the same intervention 10 days a month for 8 months. RESULTS: Results confirmed how the t-DCS intervention was effective both in the short- and the long-term to slow down the progression of AD on specific neurophysiological domains and, to a certain extent, on neurophysiological activity. Discussion tDCS appear to be effective and to affect differently neurocognitive and neurophysiological functions when comparing short and long-term outcomes. Conclusions Anodal-tDCS is an effective way to slow down the progression of Alzheimer's both in the short and long term. It can also affect the EEG patterns, but this requires a more protracted intervention.

Physical and mental health in the oldest-old: a mixed-methods study on a southern Italy sample.

BACKGROUND: The world's aging population has been constantly increasing in the last decades, causing the number oldest-old individuals to increase. AIMS: The present study aims to explore the different variables that contribute to the oldest-old wellbeing using a mixed-methods approach, including self-reports, standardized measures, and semi-structured interviews. METHODS: Thirty-nine oldest-old (90-103) from southern Italy were involved in the study, together with a control sample of younger individuals (51-71) from the same families. RESULTS: Data suggest that the oldest-old have better mental health, higher resilience, and more optimism than younger individuals. High resilience seems to be the key variable that promotes the overall wellbeing. DISCUSSION: The oldest-old tend to have better mental health, higher resilience and more optimism than younger individuals. CONCLUSIONS: Wellbeing in the oldest-old appeared to be promoted by the sense of belonging and life purpose.

Physiological levels of chromogranin A prevent doxorubicin-induced cardiotoxicity without impairing its anticancer activity.

The clinical use of doxorubicin (Doxo), a widely used anticancer chemotherapeutic drug, is limited by dose-dependent cardiotoxicity. We have investigated whether chromogranin A (CgA), a cardioregulatory protein released in the blood by the neuroendocrine system and by the heart itself, may contribute to regulation of the cardiotoxic and antitumor activities of Doxo. The effects of a physiologic dose of full-length recombinant CgA on Doxo-induced cardiotoxicity and antitumor activity were investigated in rats using in vivo and ex vivo models and in murine models of melanoma, fibrosarcoma, lymphoma, and lung cancer, respectively. The effect of Doxo on circulating levels of CgA was also investigated. In vivo and ex vivo mechanistic studies showed that CgA can prevent Doxo-induced heart inflammation, oxidative stress, apoptosis, fibrosis, and ischemic injury. On the other hand, CgA did not impair the anticancer activity of Doxo in all the murine models investigated. Furthermore, we observed that Doxo can reduce the intracardiac expression and release of CgA in the blood (i.e., an important cardioprotective agent). These findings suggest that administration of low-dose CgA to patients with low levels of endogenous CgA might represent a novel approach to prevent Doxo-induced adverse events without impairing antitumor effects.-Rocca, C., Scavello, F., Colombo, B., Gasparri, A. M., Dallatomasina, A., Granieri, M. C., Amelio, D., Pasqua, T., Cerra, M. C., Tota, B., Corti, A., Angelone, T. Physiological levels of chromogranin A prevent doxorubicin-induced cardiotoxicity without impairing its anticancer activity.

NGR-TNF Engineering with an N-Terminal Serine Reduces Degradation and Post-Translational Modifications and Improves Its Tumor-Targeting Activity.

The therapeutic index of cytokines in cancer therapy can be increased by targeting strategies based on protein engineering with peptides containing the CNGRC (NGR) motif, a ligand that recognizes CD13-positive tumor vessels. We show here that the targeting domain of recombinant CNGRC-cytokine fusion proteins, such as NGR-TNF (a CNGRC-tumor necrosis factor-α (TNF) conjugate used in clinical studies) and NGR-EMAP-II, undergoes various post-translational modification and degradation reactions that lead to the formation of markedly heterogeneous products. These modifications include N-terminal cysteine acetylation or the formation of various asparagine degradation products, the latter owing to intramolecular interactions of the cysteine α-amino group with asparagine and/or its succinimide derivative. Blocking the cysteine α-amino group with a serine (SCNGRC) reduced both post-translational and degradation reactions. Furthermore, the serine residue reduced the asparagine deamidation rate to isoaspartate (another degradation product) and improved the affinity of NGR for CD13. Accordingly, genetic engineering of NGR-TNF with the N-terminal serine produced a more stable and homogeneous drug (called S-NGR-TNF) with improved antitumor activity in tumor-bearing mice, either when used alone or in combination with chemotherapy. In conclusion, the targeting domain of NGR-cytokine conjugates can undergo various untoward modification and degradation reactions, which can be markedly reduced by fusing a serine to the N-terminus. The SCNGRC peptide may represent a ligand for cytokine delivery to tumors more robust than conventional CNGRC. The S-NGR-TNF conjugate (more stable, homogeneous, and active than NGR-TNF) could be rapidly developed for clinical trials.

Serum adiponectin levels are associated with presence of carotid plaque in women with systemic lupus erythematosus.

BACKGROUND AND AIM: Systemic lupus erythematosus (SLE) is associated with accelerated atherogenesis. Traditional risk factors do not seem to fully explain this process in patients with SLE and no other imaging/serum biomarkers have so far improved risk stratification. Here, we focused on the role of adiponectin in women with SLE. METHODS AND RESULTS: This is a sub-analysis of a validated cohort enrolling eighty females (age 18-65 years) affected by SLE. Patient underwent a single blood sampling and carotid echography. Serum adipocytokines (i.e. leptin, resistin and adiponectin) were assessed by enzyme-linked immunosorbent assay (ELISA). Patients with a carotid plaque (n = 23) were older, with longer duration of the disease, chronic use of corticosteroids, and immunosuppressive therapies. As expected, patients with a carotid plaque had increased vascular risk and high serum levels of inflammatory biomarkers, total and LDL cholesterol and adiponectin. Significant positive correlation between serum adiponectin and presence of a carotid plaque was found independently of patient age, SCORE Risk Charts, duration of disease, and SLE treatments. CONCLUSIONS: These results indicate that high serum adiponectin is associated with accelerated carotid atherosclerosis in SLE young women and it might be useful to improve vascular risk stratification in this patient setting.

The relationship between cognitive reserve and personality traits: a pilot study on a healthy aging Italian sample.

BACKGROUND: Exploring the role of different individual factors in affecting the cognitive reserve levels is crucial step for aging research. Several studies explored the relationship between personality traits and aging, but a specific focus on the cognitive reserve is missing. AIMS: This study aimed at collecting more direct evidence about possible relationships between cognitive reserve and personality traits. METHODS: A sample of 100 healthy aging participants was involved in the study. They completed the Big Five personality inventory and a test to assess the cognitive reserve. RESULTS: Results returned a positive relationship between the personality traits and participants' cognitive reserve. The only factor that did not return a significant correlation was Emotional stability (which overlaps with Neuroticism). DISCUSSION: This study provides additional evidence to the existing literature and also adds relevant information and a critical reading regarding the role of personality traits that has been neglected in the aging literature, Friendliness and Conscientiousness. CONCLUSION: The ability to measure and identify personality traits could be important in future research for developing interventions or activities that could target specific personality characteristics.

Serum osteopontin negatively impacts on intima-media thickness in patients with systemic lupus erythematosus.

BACKGROUND: Ultrasound evaluation of carotid intima-media thickness (cIMT) has been extensively used for potentially improving cardiovascular (CV) risk stratification in several patients' categories. Subjects with systemic lupus erythematosus (SLE) have been investigated by both imaging and molecular biomarker approaches with contrasting results. Here, we focused on the role of osteopontin (OPN) as biomarker of subclinical atherosclerosis associated with SLE. MATERIALS AND METHODS: Eighty females (age 18-65 years) affected by SLE and eighty age-matched healthy female controls without a clinical history of CV disease underwent ultrasound evaluation of cIMT and blood sample assay of high-sensitivity C-reactive protein (hs-CRP) and OPN. RESULTS: Healthy controls and SLE patients significantly differed for CV risk factors (ie, waist circumference, hypertension and dyslipidaemia) and the inflammatory status. Noteworthy, an opposite association between cIMT and OPN was observed in the two study groups. Whereas OPN was positively associated with mean cIMT (r = 0.364; P = 0.001) in SLE patients, a negative correlation was found in healthy controls. Furthermore, in SLE patients increased circulating levels of OPN were associated with the use of hydroxychloroquine and the positivity for the anti-dsDNA autoantibodies. At linear regression analysis, only OPN remained independently associated with cIMT also after adjustment for age, smoking pack-year, Heart SCORE, disease length and steroid therapy length. CONCLUSIONS: These results indicate that serum OPN levels were strongly associated with subclinical atherosclerosis in patients with LES and it might be a useful CV biomarker that requires additional validation in larger trials.

Association between preoperative Vasostatin-1 and pathological features of aggressiveness in localized nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET).

BACKGROUND: A reliable and accessible biomarker for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET) is currently unavailable. Chromogranin A (CgA) represents the best-described neuroendocrine biomarker, but its accuracy is low. Vasostatin-1 (VS-1), a fragment derived from the cleavage of CgA, was recently investigated and found to be more accurate as tumor biomarker in a cohort of patients affected by mainly metastatic small intestinal NET. METHODS: Patients submitted to surgery for sporadic localized NF-PanNET at San Raffaele Hospital were included. Preoperative plasma samples were prospectively collected. Circulating levels of total-CgA and VS-1 were retrospectively investigated by sandwich Enzyme-Linked ImmunoSorbent Assays. RESULTS: Overall, 50 patients were included. VS-1 value (P=0.0001) was the only preoperatively retrievable factor independently associated with NF-PanNET size. No significant correlation between CgA and tumor diameter was found (P = 0.057). A VS-1 value of 0.39 nM was identified as the optimal VS-1 cut-off accurately associated with NF-PanNET larger than 4 cm. Patients with VS-1 > 0.39 nM had a significantly higher frequency of microvascular invasion (P = 0.005) and nodal metastasis (P = 0.027). Median VS-1 plasma level was significantly higher in the presence of microvascular invasion (P = 0.001) and nodal metastasis (P = 0.012). PPI assumption significantly increased total-CgA levels, but not those of VS-1 (P = 0.111). CONCLUSIONS: In localized, non-metastatic NF-PanNET, VS-1 is strongly associated to tumor dimension and its plasma levels are significantly higher in the presence of microvascular invasion and nodal metastases; moreover, VS-1 value is not affected by the PPI use.

Using a Reminiscence-based Approach to Investigate the Cognitive Reserve of a Healthy Aging Population.

Objectives: The concept of Cognitive Reserve (CR) has been used to account for brain plasticity in older adults that may underlie the resilience against the effects of aging or pathology on cognitive abilities. This study aims at exploring the proxies of CR in a sample of healthy older adults by analyzing their spontaneous reminiscence through a discourse analysis approach. Method: Fifteen community-dwelling older adults were asked to participate in a video-recorded, spontaneous reminiscence interview. Interviews were transcribed according to Conversation Analysis, and two judges classified the interview content identifying five main markers of CR: enriched environment, cognitively stimulating activities, education, physical activity, and social interaction. Results: Reminiscence allowed to identify markers of CR. Sharing stories that are linked to CR markers promote positive emotion, coherent sense of self, and cognitive evaluation of the importance of the social network. Conclusions: Reminisce looks like a possible approach not only to indirect evaluate the CR, but also to promote it. Clinical Implications: The reminisce approach can be used as a clinical tool to assess and increase the CR, help the clinical population to experience more positive emotions, maintain a more defined sense of self, and value more the social resources available.

The influence of the dorsolateral prefrontal cortex on attentional behavior and decision making. A t-DCS study on emotionally vs. functionally designed objects.

Prior research has shown that right dorsolateral prefrontal cortex may be crucial in cognitive control of affective impulses during decision making. The present study examines whether modulation of r-DLPFC with transcranial direct current stimulation influences attentional behavior and decision-making in a purchase task requiring participants to choose either emotional/attractive or functional/useful objects. 30 participants were shown sixteen pairs of emotionally or functionally designed products while their eye-movements were recorded. Participants were asked to judge aesthetics and usefulness of each object, and to decide which object of each pair they would buy. Results revealed that participants decided to buy the functionally designed objects more often regardless of condition; however, participants receiving anodal stimulation were faster in decision making. Although stimulation of r-DLPFC did not affect the actual purchasing choice and had little effect on visual exploration during decision making, it influenced perceived usefulness and attractiveness, with temporary inhibition of r-DLPFC leading to evaluate functional objects as less attractive. Finally, anodal stimulation led to judge the objects as more useful. The implications of these results are discussed.

A new chromogranin A-dependent angiogenic switch activated by thrombin.

Angiogenesis, the formation of blood vessels from pre-existing vasculature, is regulated by a complex interplay of anti and proangiogenic factors. We found that physiologic levels of circulating chromogranin A (CgA), a protein secreted by the neuroendocrine system, can inhibit angiogenesis in various in vitro and in vivo experimental models. Structure-activity studies showed that a functional anti-angiogenic site is located in the C-terminal region, whereas a latent anti-angiogenic site, activated by cleavage of Q76-K77 bond, is present in the N-terminal domain. Cleavage of CgA by thrombin abrogated its anti-angiogenic activity and generated fragments (lacking the C-terminal region) endowed of potent proangiogenic activity. Hematologic studies showed that biologically relevant levels of forms of full-length CgA and CgA1-76 (anti-angiogenic) and lower levels of fragments lacking the C-terminal region (proangiogenic) are present in circulation in healthy subjects. Blood coagulation caused, in a thrombin-dependent manner, almost complete conversion of CgA into fragments lacking the C-terminal region. These results suggest that the CgA-related circulating polypeptides form a balance of anti and proangiogenic factors tightly regulated by proteolysis. Thrombin-induced alteration of this balance could provide a novel mechanism for triggering angiogenesis in pathophysiologic conditions characterized by prothrombin activation.

Personality characteristics, music-listening, and well-being: a systematic and scoping review.

When researchers and clinicians try to identify appropriate and effective ways to improve well-being among different populations, music is often included in interventions or research projects. The existing literature has consistently reported interactions between the effects of personality traits and music listening. However, the interrelations between individual traits and well-being after music listening are still partially unclear. This systematic review, registered on PROSPERO, investigates the relationship between everyday music listening, individual characteristics - operationalized as stable and transient personality traits - and well-being. Articles were searched on PubMed, Scopus, and Google Scholar, with a final result of 115 records. After eligibility screening, eight studies were included in the review. The results showed that both stable and transient personality traits influence music's effect on well-being. As a result of the scoping review, a theoretical perspective combining the emotional dimension, the principle of emotional congruence, and the dimension of music immersion and well-being was identified. Based on this knowledge, music listening could be systematically introduced into daily routines to improve everyday well-being and prevent or reduce stressful states.

The Effect of COVID-19 on Middle-Aged Adults' Mental Health: A Mixed-Method Case-Control Study on the Moderating Effect of Cognitive Reserve.

The COVID-19 pandemic has increased the vulnerability of adults to mental health effects, and the study of protective factors has become crucial. Cognitive reserve (CR) is a well-known protective factor against cognitive decline and several health factors; however, its protective effect on mental health during the pandemic has been rarely addressed. Thus, this study explored, through a mixed-method design, the effect of CR on perceived distress and PTSD-like symptoms in middle-aged participants who have survived severe COVID-19 and a matched control group. A total of 432 participants filled out self-report measures of CR, PTSD, depression, and anxiety, and were also asked to provide narration about their COVID-19-related experience. COVID-19 significantly affected the chances of reporting different mental health symptoms; levels of CR played a protective role in reducing their severity. Moreover, adults with higher CR seemed to be more realistic, focusing less on positive emotions, and elaborating more on the sense of anxiety when describing their experience: this might be an indication of a lower use of suppression to regulate emotions. Practical implications of these findings and future directions have been also discussed.

IsoDGR-tagged albumin: a new αvß3 selective carrier for nanodrug delivery to tumors.

A new cyclic peptide containing the isoDGR motif that, after coupling to albumin, selectively binds αvß3, an integrin overexpressed in the tumor vasculature. IsoDGR-tagged albumin binds tumor vessels and can be exploited as a carrier for the preparation of tumor vasculature-selective nanomedicines, such as gold nanoparticles (Au) carrying tumor necrosis factor α (TNF), a potent vascular damaging agent.