A5020250628- Immunotherapy and Immune Responses
- Nanoparticle-Based Drug Delivery
- Cancer Research and Treatments
- RNA Interference and Gene Delivery
- Bacteriophages and microbial interactions
- Monoclonal and Polyclonal Antibodies Research
- Toxin Mechanisms and Immunotoxins
- Supramolecular Self-Assembly in Materials
- Glycosylation and Glycoproteins Research
- Chemokine receptors and signaling
- Advanced biosensing and bioanalysis techniques
- Advanced Drug Delivery Systems
- Cancer Cells and Metastasis
- Cancer Mechanisms and Therapy
- Ovarian cancer diagnosis and treatment
- Cutaneous Melanoma Detection and Management
- Peptidase Inhibition and Analysis
- Chemical Reactions and Isotopes
- Immune cells in cancer
- Acute Myeloid Leukemia Research
- Cell Adhesion Molecules Research
- IL-33, ST2, and ILC Pathways
- Cell death mechanisms and regulation
- Polymer Surface Interaction Studies
- CAR-T cell therapy research
Josep Carreras Leukaemia Research Institute
2018-2025
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine
2015-2025
Hospital de Sant Pau
2014-2025
Instituto de Salud Carlos III
2023-2024
Institut de Recerca Sant Pau
2024
Hospital Universitario de Gran Canaria Doctor Negrín
2024
Universitat Autònoma de Barcelona
2021-2023
Fundación Josep Carreras Contra la Leucemia
2021-2022
Centro de Investigación Biomédica en Red
2012
The fully de novo design of protein building blocks for self-assembling as functional nanoparticles is a challenging task in emerging nanomedicines, which urgently demand novel, versatile, and biologically safe vehicles imaging, drug delivery, gene therapy. While the use viruses virus-like particles limited by severe constraints, generation protein-only nanocarriers progressively reachable engineering protein-protein interactions, resulting blocks. In particular, end-terminal cationic...
Research Article6 September 2018Open Access Transparent process Selective depletion of metastatic stem cells as therapy for human colorectal cancer María Virtudes Céspedes Institut d'Investigacions Biomèdiques Sant Pau, Hospital de Santa Creu i Barcelona, Spain CIBER Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Search more papers by this author Ugutz Unzueta Anna Aviñó Institute Advanced Chemistry Catalonia (IQAC), CSIC, Alberto Gallardo Department Pathology, la Patricia Álamo...
Abstract Background Current acute myeloid leukemia (AML) therapy fails to eliminate quiescent leukemic blasts in the bone marrow, leading about 50% of patient relapse by increasing AML burden blood, and extramedullar sites. We developed a protein-based nanoparticle conjugated potent antimitotic agent Auristatin E that selectively targets because their CXCR4 receptor overexpression (CXCR4+) as compared normal cells. The therapeutic rationale is based on involvement blast homing quiescence...
Therapy resistance, which leads to the development of loco-regional relapses and distant metastases after treatment, constitutes one major problems that head neck squamous cell carcinoma (HNSCC) patients currently face. Thus, novel therapeutic strategies are urgently needed. Targeted drug delivery chemokine receptor 4 (CXCR4) represents a promising approach for HNSCC management. In this context, we have developed self-assembling protein nanotoxins T22-PE24-H6 T22-DITOX-H6, incorporate...
Developing time-sustained drug delivery systems is a main goal in innovative medicines. Inspired by the architecture of secretory granules from mammalian endocrine system it has generated non-toxic microscale amyloid materials through coordination between divalent metals and poly-histidine stretches. Like their natural counterparts that keep functionalities assembled protein, those synthetic structures release biologically active proteins during slow self-disintegration process occurring...
Abstract Functional amyloids produced in bacteria as nanoscale inclusion bodies are intriguing but poorly explored protein materials with wide therapeutic potential. Since they release functional polypeptides under physiological conditions, these can be potentially tailored mimetic of secretory granules for slow systemic delivery smart drugs. To explore this possibility, bacterial formed by a self‐assembled, tumor‐targeted Pseudomonas exotoxin (PE24) administered subcutaneously mouse models...
Bacterial inclusion bodies (IBs) are mechanically stable protein particles in the microscale, which behave as robust, slow-protein-releasing amyloids. Upon exposure to cultured cells or upon subcutaneous intratumor injection, these materials secrete functional IB polypeptides, functionally mimicking endocrine release of peptide hormones from secretory amyloid granules. Being appealing delivery systems for prolonged drug release, development IBs toward clinical applications is, however,...
Colorectal cancer (CRC) remains the third cause of cancer-related mortality in Western countries, metastases are main death. CRC treatment limited by systemic toxicity and chemotherapy resistance. Therefore, nanoparticle-mediated delivery cytotoxic agents selectively to cells represents an efficient strategy increase therapeutic index overcome drug We have developed T22-PE24-H6 protein-only nanoparticle that incorporates exotoxin A from Pseudomonas aeruginosa target because its multivalent...
Although all KRas (protein that in humans is encoded by the gene) point mutants are considered to have a similar prognostic capacity, their transformation and tumorigenic capacities vary widely. We compared metastatic efficiency of G12V (Kirsten rat sarcoma viral oncogene homolog with valine mutation at codon 12) G13D aspartic 13) oncogenes an orthotopic colorectal cancer (CRC) model. Following subcutaneous preconditioning, recombinant clones SW48 CRC cell line [Kras wild-type (Kras WT)]...
Fluorescent dye labeling is a common strategy to analyze the fate of administered nanoparticles in living organisms. However, which extent processes can alter original nanoparticle biodistribution has been so far neglected. In this work, two widely used fluorescent molecules, namely, ATTO488 (ATTO) and Sulfo-Cy5 (S-Cy5), have covalently attached well-characterized CXCR4-targeted self-assembling protein (known as T22-GFP-H6). The labeled T22-GFP-H6-ATTO T22-GFP-H6-S-Cy5 then compared that...
Colorectal cancer (CRC) has traditionally been treated with genotoxic chemotherapy to activate pro-apoptotic proteins induce anticancer effects. However, cells develop resistance apoptosis, which leads recurrence and poor prognosis. Moreover, this kind of therapy shown be highly toxic healthy tissues and, therefore, patients. To overcome issue, we developed a self-assembly tumor-targeted nanoparticle, T22-DITOX-H6, that incorporates the T22 peptide (a CXCR4 ligand) selectively target...
Abstract In the human endocrine system many protein hormones including urotensin, glucagon, obestatin, bombesin and secretin, among others, are supplied from amyloidal secretory granules. These granules form part of so called functional amyloids, which within whole aggregome appear to be more abundant than formerly believed. Bacterial inclusion bodies (IBs) non-toxic, nanostructured amyloids whose biological fabrication can tailored render materials with defined biophysical properties. Since...
Background: Novel therapeutic strategies are urgently needed to reduce relapse rates and enhance survival in Diffuse Large B-Cell Lymphoma (DLBCL) patients. CXCR4-overexpressing cancer cells good targets for therapy because of their association with dissemination R-CHOP treated DLBCL Immunotoxins that incorporate bacterial toxins potentially effective treating haematological neoplasias, but show a narrow index due the induction severe side effects. Therefore, when considering delivery these...
Loco-regional recurrences and distant metastases represent the main cause of head neck squamous cell carcinoma (HNSCC) mortality. The overexpression chemokine receptor 4 (CXCR4) in HNSCC primary tumors associates with higher risk developing loco-regional metastases, thus making CXCR4 an ideal entry pathway for targeted drug delivery. In this context, our group has generated self-assembling protein nanocarrier T22-GFP-H6, displaying multiple T22 peptidic ligands that specifically target...
Background and Purpose: Around 40– 50% of diffuse large-B cell lymphoma (DLBCL) patients suffer from refractory disease or relapse after R-CHOP first-line treatment. Many ongoing clinical trials for DLBCL involve microtubule targeting agents (MTAs), however, their anticancer activity is limited by severe side effects. Therefore, we chose to improve the therapeutic window MTA monomethyl auristatin E developing a nanoconjugate, T22-AUR, that selectively targets CXCR4 receptor, which...
Current therapy in acute myeloid leukemia (AML) is based on chemotherapeutic drugs administered at high doses, lacking targeting selectivity and displaying poor therapeutic index because of severe adverse effects. Here, we develop a novel nanoconjugate that combines self-assembled, multivalent protein nanoparticle, the CXCR4 receptor, with an Oligo-Ara-C prodrug, pentameric form Ara-C, to highly increase delivered payload target cells. This 13.4 nm T22-GFP-H6-Ara-C selectively eliminates...
The development of new and more efficient vaccination approaches is a constant need, due to the pressure historical emerging infectious diseases limited efficacy universality current technologies. Peptides recombinant proteins have been explored for decades as subunit vaccines bacterial viral infections, presented either soluble protein species or virus-like assemblies. Recently, synthetic secretory protein-only microscale granules developed dynamic depots sustained release. They are based...