Person: Moreno Zafra, Víctor Manuel
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First Name
Víctor Manuel
Last Name
Moreno Zafra
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Química en Ciencias Farmacéuticas
Area
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6 results
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Now showing 1 - 6 of 6
- PublicationHybrid nanosystems for the delivery of therapeutic agents as tretament for complex diseases(Universidad Complutense de Madrid, 2021-09-09) Moreno Zafra, Víctor Manuel; Vallet Regí, María; Baeza García, AlejandroThe overall objective of this doctoral thesis has been the design of various nanomaterials with the aim of addressing distinct approaches to treat cancer and fibrosis, as well as overcoming some of the biological barriers that restrict nanomedicine-based therapies.These biological restrictions entail important limitations in the fight against cancer based on nanomedicines. Some of them are the sequestration of nanoparticles by the mononuclear phagocytic system, the lack of selectivity of conventional chemotherapy, which generates undesirable side-effects and disfunctions in organs or tissues, or the scarce penetration of nanoparticles within the target diseased tissue. Recent interest in the design of nanosystems that overcome these constraints is generating new tools for the effective treatment of cancer, as well as other pathologies...
- PublicationUVA-degradable Collagenase Nanocapsules as a potential treatment for fibrotic disease.(MDPI, 2021-04-06) Moreno Zafra, Víctor Manuel; Meroño, Carolina; Baeza, Alejandro; Usategui Corral, Alicia; Ortiz-Romero, Pablo L.; Pablos, José L.; Vallet Regí, MaríaPeyronie and Dupuytren are pathologies characterized by the appearance of localized fibrotic lesions in an organ. These disorders originate from an excessive production of collagen in the tissue provoking dysfunction and functional limitations to the patients. Local administration of collagenase is the most used treatment for these fibrotic-type diseases, but a high lability of the enzyme limits its therapeutic efficacy. Herein, we present a novel methodology for the preparation of collagenase nanocapsules without affecting its enzymatic activity and capable of releasing the enzyme in response to an ultraviolet A (UVA) light stimulus. Polymeric coating around collagenase was formed by free-radical polymerization of acrylamide-type monomers. Their degradation capacity under UVA irradiation was provided by incorporating a novel photocleavable acrylamide-type crosslinker within the polymeric framework. This property allowed collagenase release to be triggered in a controlled manner by employing an easily focused stimulus. Additionally, UVA irradiation presents considerable benefits by itself due to its capacity to induce collagenase production in situ. An expected synergistic effect of collagenase nanocapsules in conjunction with UVA effect may present a promising treatment for these fibrotic diseases.
- PublicationBacteria as Nanoparticles Carrier for Enhancing Penetration in a Tumoral Matrix Model(Wiley Online Library, 2020-04-21) Moreno Zafra, Víctor Manuel; Alvarez Corchado, Elena; Izquierdo-Barba, Isabel; Baeza, Alejandro; Serrano López, Juana; Vallet Regí, MaríaOne of the major concerns in the application of nanocarriers in oncology is their scarce penetration capacity in tumoral tissues, which drastically compromises the effectivity. Living organisms as cells and bacteria present the capacity to navigate autonomously following chemical gradients being able to penetrate deeply into dense tissues. In the recent years, the possibility to employ these organisms for the transportation of therapeutic agents and nanocarriers attached on their membrane or engulfed in their inner space have received huge attention. Herein, based on this principle, a new approach to deliver drug loaded nanoparticles achieving high penetration in tumoral matrices is presented. In this case, Escherichia coli (E. coli) bacteria wall is decorated with azide groups, whereas alkyne-strained groups are incorporated on the surface of mesoporous silica nanoparticles loaded with a potent cytotoxic compound, doxorubicin. Both functional groups form stable triazole bonds by click-type reaction allowing the covalent grafting of nanoparticles on living bacteria. Thus, the motility and penetration capacity of bacteria, which carried nanoparticles are evaluated in a 3D tumoral matrix model composed by a dense collagen extracellular matrix with HT1080 human fibrosarcome cells embedded. The results confirmed that bacteria are able to transport the nanoparticles crossing a thick collagen layer being able to destroy almost 80% of the tumoral cells located underneath. These findings envision a powerful strategy in nanomedicine applied for cancer treatment by Q4 allowing a homogeneous distribution of therapeutic agents in the malignancy.
- PublicationBacteria as Nanoparticle Carriers for Immunotherapy in Oncology(MPDI, 2022-04-03) Moreno Zafra, Víctor Manuel; Baeza, AlejandroThe use of nanocarriers to deliver antitumor agents to solid tumors must overcome biological barriers in order to provide effective clinical responses. Once within the tumor, a nanocarrier should navigate into a dense extracellular matrix, overcoming intratumoral pressure to push it out of the diseased tissue. In recent years, a paradigm change has been proposed, shifting the target of nanomedicine from the tumoral cells to the immune system, in order to exploit the natural ability of this system to capture and interact with nanometric moieties. Thus, nanocarriers have been engineered to interact with immune cells, with the aim of triggering specific antitumor responses. The use of bacteria as nanoparticle carriers has been proposed as a valuable strategy to improve both the accumulation of nanomedicines in solid tumors and their penetration into the malignancy. These microorganisms are capable of propelling themselves into biological environments and navigating through the tumor, guided by the presence of specific molecules secreted by the diseased tissue. These capacities, in addition to the natural immunogenic nature of bacteria, can be exploited to design more effective immunotherapies that yield potent synergistic effects to induce efficient and selective immune responses that lead to the complete eradication of the tumor.
- PublicationBacteria-Assisted Transport of Nanomaterials to Improve Drug Delivery in Cancer Therapy(MDPI, 2022-01-17) Jiménez Jiménez, Carla; Moreno Zafra, Víctor Manuel; Vallet Regí, MaríaCurrently, the design of nanomaterials for the treatment of different pathologies is presenting a major impact on biomedical research. Thanks to this, nanoparticles represent a successful strat-egy for the delivery of high amounts of drugs for the treatment of cancer. Different nanosystems have been designed to combat this pathology. However, the poor penetration of these nano-materials into the tumor tissue prevents the drug from entering the inner regions of the tumor. Some bacterial strains have self-propulsion and guiding capacity thanks to their flagella. They also have a preference to accumulate in certain tumor regions due to the presence of different chemo-attractants factors. Bioconjugation reactions allow the binding of nanoparticles in living systems, such as cells or bacteria, in a simple way. Therefore, bacteria are being used as a transport vehicle for nanoparticles, facilitating their penetration and the subsequent release of the drug inside the tumor. This review would summarize the literature on the anchoring meth-ods of diverse nanosystems in bacteria and, interestingly, their advantages and possible applica-tions in cancer therapy.
- PublicationEvaluation of the Penetration Process of Fluorescent Collagenase Nanocapsules in a 3D Collagen Gel(Elsevier, 2020-12-10) Moreno Zafra, Víctor Manuel; Baeza, Alejandro; Vallet Regí, MaríaOne of the major limitations of nanomedicine is the scarce penetration of nanoparticles in tumoral tissues. These constrains have been tried to be solved by different strategies, such as the employ of polyethyleneglycol (PEG) to avoid the opsonization or reducing the extracellular matrix (ECM) density. Our research group has developed some strategies to overcome these limitations such as the employ of pH-sensitive collagenase nanocapsules for the digestion of the collagen-rich extracellular matrix present in most of tumoral tissues. However, a deeper understanding of physicochemical kinetics involved in the nanocapsules degradation process is needed to understand the nanocapsule framework degradation process produced during the penetration in the tissue. For this, in this work it has been employed a double-fluorescent labelling strategy of the polymeric enzyme nanocapsule as a crucial chemical tool which allowed the analysis of nanocapsules and free collagenase during the diffusion process throughout a tumour-like collagen matrix. This extrinsic label strategy provides far greater advantages for observing biological processes. For the detection of enzyme, collagenase has been labelled with fluorescein Isothiocyanate (FITC), whereas the nanocapsule surface was labelled with rhodamine Isothiocyanate (RITC). Thus, it has been possible to monitor the hydrolysis of nanocapsules and their diffusion throughout a thick 3D Collagen gel during the time, obtaining a detailed temporal evaluation of the pH-sensitive collagenase nanocapsule behaviour. These collagenase nanocapsules displayed a high enzymatic activity in low concentrations at acidic pH, and their efficiency to penetrate into tissue models pave the way to a wide range of possible nanomedical applications, especially in cancer therapy.