63 research outputs found
Solid-Phase Synthesized Copolymers for the Assembly of pH-Sensitive Micelles Suitable for Drug Delivery Applications
No full textDiblock copolymers of polyhistidine are known for their self-assembly into micelles and their pH-dependent disassembly due to the amphiphilic character of the copolymer and the unsaturated imidazole groups that undergo a hydrophobic-to-hydrophilic transition in an acidic pH. This property has been largely utilized for the design of drug delivery systems that target a tumor environment possessing a slightly lower extracellular pH (6.8–7.2). The main purpose of this study was to investigate the possibility of designed poly(ethylene glycol)-polyhistidine sequences synthesized using solid-phase peptide synthesis (SPPS), to self-assemble into micelles, to assess the ability of the corresponding micelles to be loaded with doxorubicin (DOX), and to investigate the drug release profile at pH values similar to a malignant extracellular environment. The designed and assembled free and DOX-loaded micelles were characterized from a physico-chemical point of view, their cytotoxicity was evaluated on a human breast cancer cell line (MDA-MB-231), while the cellular areas where micelles disassembled and released DOX were assessed using immunofluorescence. We concluded that the utilization of SPPS for the synthesis of the polyhistidine diblock copolymers yielded sequences that behaved similarly to the copolymeric sequences synthesized using ring-opening polymerization, while the advantages of SPPS may offer facile tuning of the histidine site or the attachment of a large variety of functional molecules
Collagen-Binding Nanoparticles: A Scoping Review of Methods and Outcomes
No full text(1) Background: Collagen is the main component of the connective tissue, playing an important role in the histological architecture and function of living organisms. Targeted therapy and improved imaging diagnosis can be obtained through collagen-binding nanoparticles that concentrate in the extracellular matrix. (2) Methods: We performed a scoping review of studies that analyzed the binding capacity of collagen-targeting nanoparticles. The search algorithm and inclusion criteria were based on PRISMA and ARRIVE guidelines. (3) Results: Fourteen studies matched all the inclusion criteria. All studies analyzed the distribution of nanoparticles in the collagen matrix, either by using collagen-targeting nanoparticles or by using unmodified ones. Most studies used collagen-binding nanoparticles for vascular research to target sites of endothelial injury, atherosclerotic plaques, or myocardial infarction. Two studies targeted the exposed collagen in models of liver fibrosis. (4) Conclusions: Our review summarizes the current literature on the methods and outcomes of using nanoparticles to target collagen. The studies reveal that there is high applicability for collagen-binding nanoparticles in cardiac or hepatic pathology and they could prove useful for targeted therapy of neoplastic lesions, which show an abundance of stromal collagen
Quantum modularity and complex Chern-Simons theory
No full textThe Quantum Modularity Conjecture of Zagier predicts the existence of a formal power series with arithmetically interesting coefficients that appears in the asymptotics of the Kashaev invariant at each root of unity. Our goal is to construct a power series from a Neumann-Zagier datum (i.e., an ideal triangulation of the knot complement and a geometric solution to the gluing equations) and a complex root of unity ζ. We prove that the coefficients of our series lie in the trace field of the knot, adjoined a complex root of unity. We conjecture that our series are those that appear in the Quantum Modularity Conjecture and confirm that they match the numerical asymptotics of the Kashaev invariant (at various roots of unity) computed by Zagier and the first author. Our construction is motivated by the analysis of singular limits in Chern-Simons theory with gauge group SL(2,C) at fixed level k, where ζk=1
CD133 and CD166 Stem Cells Markers Expression, Clinicopathological Parameters, and Fragmentation Response Patterns of ypT3 Rectal Cancer Following Neoadjuvant Chemoradiotherapy
No full textBackground: The effectiveness of neoadjuvant chemoradiotherapy (nCRT) is variable in locally advanced rectal cancer (LARC) patients, the ypT3 stage having a minimal or moderate response. The aim of our study was the evaluation of the association between CD133 (Prominin1) and CD166 (ALCAM) expression, survival parameters, and clinicopathological characteristics of a subgroup of LARC patients who achieved ypT3, showing post-nCRT and TME tumor fragmentation response and the assessment of these CSCs biomarkers value as indicators of the nCRT tumor response. Methods: Our study group comprised 60 LARC patients who achieved ypT3 status and exhibited a tumor fragmentation pattern following nCRT. Clinicopathological parameter and survival evaluations, along with CD133 and CD166 immunohistochemistry and scoring, were performed and the associations between different parameters were tested. Results: High CD133 expression was significantly associated with ypN category (p = 0.018), lymphovascular invasion (LVI) (p = 0.009), perineural invasion (PnI) (p = 0.006), and tumor grading (p = 0.047), while high CD166 expression was significantly associated with LVI (p = 0.020) and PnI (p = 0.028). Tumors with high CD133 and CD166 expressions were associated with decreased overall survival (OS) (p = 0.004 and p = 0.006). Cox regression analysis identified high CD133 and CD166 expression as independent factors associated with reduced survival (HR = 3.237, p = 0.014 and HR = 2.866, p = 0.020). Conclusions: Our results support the hypothesis that CD133 and CD166 are putative CSC biomarkers associated with aggressive behavior and a poor prognosis in LARC, offering opportunities for personalized targeted therapies
Targeted Chemotherapy Delivery via Gold Nanoparticles: A Scoping Review of In Vivo Studies
No full textIn the field of oncology, a lot of improvements in nanotechnology creates support for better diagnosis and therapeutic opportunities, and due to their physical and chemical properties, gold nanoparticles are highly applicable. We performed a literature review on the studies engaging the usage of gold nanoparticles on murine models with a focus on the type of the carrier, the chemotherapy drug, the target tumoral tissue and outcomes. We identified fifteen studies that fulfilled our search criteria, in which we analyzed the synthesis methods, the most used chemotherapy conjugates of gold nanoparticles in experimental cancer treatment, as well as the improved impact on tumor size and system toxicity. Due to their intrinsic traits, we conclude that chemotherapy conjugates of gold nanoparticles are promising in experimental cancer treatment and may prove to be a safer and improved therapy option than current alternatives
Clostridium difficile Colonization in Oncologic Patients Undergoing Major Abdominopelvic Surgery: To Treat or Not to Treat? An Observational Study with Propensity Score Analysis
No full textBackground: Clostridium difficile colonization (CDC) represents a clinical concern in oncology patients undergoing abdominopelvic surgery, particularly regarding the potential role of prophylactic antibiotics in preventing progression to active infection. Methods: We performed a single-center, retrospective, case-matched observational study of oncology patients with CDC who underwent abdominopelvic surgery between 2018 and 2023. Patients were divided into two cohorts: those who received prophylactic antibiotics and those who did not. Postoperative outcomes were compared using propensity score matching (PSM). Logistic regression and ROC curve analysis were applied to assess the predictive value of antibiotics relative to other comorbidities. Results: Ninety patients were included (62 with antibiotics; 28 without). In the unmatched cohort, patients receiving antibiotics showed a non-significant trend toward higher morbidity (32.2% vs. 21.4%, p = 0.327) and surgical site infection rates (9.6% vs. 0%, p = 0.171). After PSM (26 patients per group), morbidity remained comparable between cohorts (30.7% vs. 23.0%, p = 0.538). Notably, no patient developed active C. difficile infection during follow-up, regardless of antibiotic use. Antibiotic therapy was not an independent predictor of postoperative morbidity (OR 1.746, p = 0.297; AUC 0.549, 95% CI 0.405–0.687). Conclusions: In this study, prophylactic antibiotic use in CDC patients undergoing abdominopelvic oncology surgery was not associated with improved postoperative outcomes. While no progression to active infection was observed, the potential benefits of prophylaxis remain uncertain. Larger, prospective studies are needed to clarify the clinical role of antibiotics in this setting
Targeted Cancer Therapy via pH-Functionalized Nanoparticles: A Scoping Review of Methods and Outcomes
No full text(1) Background: In recent years, several studies have described various and heterogenous methods to sensitize nanoparticles (NPs) to pH changes; therefore, in this current scoping review, we aimed to map current protocols for pH functionalization of NPs and analyze the outcomes of drug-loaded pH-functionalized NPs (pH-NPs) when delivered in vivo in tumoral tissue. (2) Methods: A systematic search of the PubMed database was performed for all published studies relating to in vivo models of anti-tumor drug delivery via pH-responsive NPs. Data on the type of NPs, the pH sensitization method, the in vivo model, the tumor cell line, the type and name of drug for targeted therapy, the type of in vivo imaging, and the method of delivery and outcomes were extracted in a separate database. (3) Results: One hundred and twenty eligible manuscripts were included. Interestingly, 45.8% of studies (n = 55) used polymers to construct nanoparticles, while others used other types, i.e., mesoporous silica (n = 15), metal (n = 8), lipids (n = 12), etc. The mean acidic pH value used in the current literature is 5.7. When exposed to in vitro acidic environment, without exception, pH-NPs released drugs inversely proportional to the pH value. pH-NPs showed an increase in tumor regression compared to controls, suggesting better targeted drug release. (4) Conclusions: pH-NPs were shown to improve drug delivery and enhance antitumoral effects in various experimental malignant cell lines
Variations in the Number of Circulating Tumor Cells During the Surgical Sequence for Locally Advanced Rectal Cancer
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