Nuria Oliva
@iqs.edu
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Aparna Loecher, Michael Bruyns-Haylett, Pedro J. Ballester, Salvador Borros, and Nuria Oliva
Royal Society of Chemistry (RSC)
Machine Learning (ML) algorithms are ideal in silico tools to find patterns of cellular internalisation of pBAE polyplexes in various cell types, using chemical and biophysical material properties and cellular gene expression as model inputs.
Anna D. Y. Rhodes, Jose Antonio Duran-Mota, and Nuria Oliva
Royal Society of Chemistry (RSC)
Biomaterials have the power to epigenetically modulate gene expression of cells in contact with it. This review article summarises the current state-of-the-art and progress on the development of bio- and nanomaterials to modulate the epigenome.
Nuria Oliva, Mikyung Shin, and Jason A. Burdick
American Chemical Society (ACS)
Jose Antonio Duran-Mota, Júlia Quintanas Yani, Benjamin D. Almquist, Salvador Borrós, and Nuria Oliva
American Chemical Society (ACS)
J. A. Duran-Mota, N. Oliva, and B. D. Almquist
The Royal Society of Chemistry
The human body is a complex system where several interconnected dynamic processes work in an orchestrated manner to carry out the many different body functions. However, pathological conditions may cause dysregulations of these body functions. Biomedicine aims to understand such dysregulations and restore normal, healthy function within bodies. A wide variety of therapeutics have been used since ancient times, but their traditional systemic administration lacks spatiotemporal control over the delivery. Recent progress in chemistry and physics, along with the emergence of nanotechnology, has allowed the development of new strategies to solve this drawback such as stimuli-responsive nanobiomaterials. This new class of materials can be designed to respond to chemical and physical stimuli associated with pathological dysregulations (for example, changes in pH or redox environment, or the increase of certain biomolecules in the bloodstream). Alternatively, stimuli can also be provided externally (such as magnetic fields or light) to trigger the controlled release of therapeutics. Hydrogels are one of the most promising materials to achieve complete spatiotemporal control as they are typically injected or implanted where they are needed. Moreover, the chemical structure of the polymers forming the hydrogel can be easily manipulated to make them stimuli-responsive. This chapter focuses on the chemical and physical mechanisms that confer stimuli-responsive properties to polymers, enabling the development of smart hydrogels for spatiotemporal delivery of drugs.
Yi Zhang, Pere Dosta, João Conde, Nuria Oliva, Mian Wang, and Natalie Artzi
Wiley
Triple negative breast cancer patients remain with chemotherapy as their only viable therapeutic option. However, the toxicity of available anticancer drugs and their inefficient delivery have limited the development of effective chemotherapy administration protocols and combination therapies. Drug delivery devices that can properly target chemotherapy to the right cells with efficient cancer‐cell killing may play a vital role in eliminating triple‐negative breast cancer. While systemic delivery results in low drug accumulation at the tumor site and for a short period of time, local delivery enables sustained drug release. However, a system that is able to provide rapid, yet prolonged action, would enable efficient tumor elimination. Herein, the development of dual‐sensitive nanogels is described that are designed to rapidly dislodge the chemotherapy drug, doxorubicin, inside cancer cells through dual‐sensitive action—pH and redox sensitivities—enabling efficient cancer‐cell killing while eliminating systemic side effects. Their embedding within a hydrogel injected next to a tumor in a triple‐negative breast‐cancer mouse model enables prolonged release of the drug with instantaneous action when inside the cells resulting in efficacious tumor elimination compared to sustained local delivery only. This technology can be used for the delivery of combination therapies and for the treatment of other solid tumors.
Nuria Oliva and Benjamin D. Almquist
Elsevier BV
Anna Stejskalová, Nuria Oliva, Frances J. England, and Benjamin D. Almquist
Wiley
Biomaterial scaffolds that are designed to incorporate dynamic, spatiotemporal information have the potential to interface with cells and tissues to direct behavior. Here, a bioinspired, programmable nanotechnology‐based platform is described that harnesses cellular traction forces to activate growth factors, eliminating the need for exogenous triggers (e.g., light), spatially diffuse triggers (e.g., enzymes, pH changes), or passive activation (e.g., hydrolysis). Flexible aptamer technology is used to create modular, synthetic mimics of the Large Latent Complex that restrains transforming growth factor‐β1 (TGF‐β1). This flexible nanotechnology‐based approach is shown here to work with both platelet‐derived growth factor‐BB (PDGF‐BB) and vascular endothelial growth factor (VEGF‐165), integrate with glass coverslips, polyacrylamide gels, and collagen scaffolds, enable activation by various cells (e.g., primary human dermal fibroblasts, HMEC‐1 endothelial cells), and unlock fundamentally new capabilities such as selective activation of growth factors by differing cell types (e.g., activation by smooth muscle cells but not fibroblasts) within clinically relevant collagen sponges.
Nuria Oliva, João Conde, Kui Wang, and Natalie Artzi
American Chemical Society (ACS)
Systemic administration of therapeutic agents has been the preferred approach to treat most pathological conditions, in particular for cancer therapy. This treatment modality is associated with side effects, off-target accumulation, toxicity, and rapid renal and hepatic clearance. Multiple efforts have focused on incorporating targeting moieties into systemic therapeutic vehicles to enhance retention and minimize clearance and side effects. However, only a small percentage of the nanoparticles administered systemically accumulate at the tumor site, leading to poor therapeutic efficacy. This has prompted researchers to call the status quo treatment regimen into question and to leverage new delivery materials and alternative administration routes to improve therapeutic outcomes. Recent approaches rely on the use of local delivery platforms that circumvent the hurdles of systemic delivery. Local administration allows delivery of higher "effective" doses while enhancing therapeutic molecules' stability, minimizing side effects, clearance, and accumulation in the liver and kidneys following systemic administration. Hydrogels have proven to be highly biocompatible materials that allow for versatile design to afford sensing and therapy at the same time. Hydrogels' chemical and physical versatility can be exploited to attain disease-triggered in situ assembly and hydrogel programmed degradation and consequent drug release, and hydrogels can also serve as a biocompatible depot for local delivery of stimuli-responsive therapeutic cargo. We will focus this Account on the hydrogel platform that we have developed in our lab, based on dendrimer amine and dextran aldehyde. This hydrogel is disease-responsive and capable of sensing the microenvironment and reacting in a graded manner to diverse pathologies to render different properties, including tissue adhesion, biocompatibility, hydrogel degradation, and embedded drug release profile. We also studied the degradation kinetics of our stimuli-responsive materials in vivo and analyzed the in vitro conditions under which in vitro-in vivo correlation is attained. Identifying key parameters in the in vivo microenvironment under healthy and disease conditions was key to attaining that correlation. The adhesive capacity of our dendrimer-dextran hydrogel makes it optimal for localized and sustained release of embedded drugs. We demonstrated that it affords the delivery of a range of therapeutics to combat cancer, including nucleic acids, small molecules, and antibody drugs. As a depot for local delivery, it allows a high dose of active biomolecules to be delivered directly at the tumor site. Immunotherapy, a recently blooming area in cancer therapy, may exploit stimuli-responsive hydrogels to impart systemic effects following localized therapy. Local delivery would enable release of the proper drug dose and improve drug bioavailability where needed at the same time creating memory and exerting the therapeutic effect systemically. This Account highlights our perspective on how local and systemic therapies provided by stimuli-responsive hydrogels should be used to impart more precise, long-lasting, and potent therapeutic outcomes.
João Conde, Nuria Oliva, Yi Zhang, and Natalie Artzi
Springer Science and Business Media LLC
Avital Gilam, João Conde, Daphna Weissglas-Volkov, Nuria Oliva, Eitan Friedman, Natalie Artzi, and Noam Shomron
Springer Science and Business Media LLC
AbstractMetastasis is the primary cause for mortality in breast cancer. MicroRNAs, gene expression master regulators, constitute an attractive candidate to control metastasis. Here we show that breast cancer metastasis can be prevented by miR-96 or miR-182 treatment, and decipher the mechanism of action. We found that miR-96/miR-182 downregulate Palladin protein levels, thereby reducing breast cancer cell migration and invasion. A common SNP, rs1071738, at the miR-96/miR-182-binding site within the Palladin 3′-UTR abolishes miRNA:mRNA binding, thus diminishing Palladin regulation by these miRNAs. Regulation is successfully restored by applying complimentary miRNAs. A hydrogel-embedded, gold-nanoparticle-based delivery vehicle provides efficient local, selective, and sustained release of miR-96/miR-182, markedly suppressing metastasis in a breast cancer mouse model. Combined delivery of the miRNAs with a chemotherapy drug, cisplatin, enables significant primary tumour shrinkage and metastasis prevention. Our data corroborate the role of miRNAs in metastasis, and suggest miR-96/miR-182 delivery as a potential anti-metastatic drug.
João Conde, Nuria Oliva, and Natalie Artzi
Elsevier BV
Anna Falanga, Armando Santoro, Roberto Labianca, Filippo De Braud, Giampietro Gasparini, Andrea D’Alessio, Sandro Barni, Licia Iacoviello, Anna Falanga, Luca Barcella,et al.
Elsevier BV
João Conde, Nuria Oliva, Mariana Atilano, Hyun Seok Song, and Natalie Artzi
Springer Science and Business Media LLC
N. Oliva and N. Artzi
IMPERIAL COLLEGE PRESS
Nuria Oliva, Shimon Unterman, Yi Zhang, João Conde, Hyun Seok Song, and Natalie Artzi
Wiley
New advances in (nano)biomaterial design coupled with the detailed study of tissue–biomaterial interactions can open a new chapter in personalized medicine, where biomaterials are chosen and designed to match specific tissue types and disease states. The notion of a “one size fits all” biomaterial no longer exists, as growing evidence points to the value of customizing material design to enhance (pre)clinical performance. The complex microenvironment in vivo at different tissue sites exhibits diverse cell types, tissue chemistry, tissue morphology, and mechanical stresses that are further altered by local pathology. This complex and dynamic environment may alter the implanted material's properties and in turn affect its in vivo performance. It is crucial, therefore, to carefully study tissue context and optimize biomaterials considering the implantation conditions. This practice would enable attaining predictable material performance and enhance clinical outcomes.
João Conde, Nuria Oliva, and Natalie Artzi
Proceedings of the National Academy of Sciences
Significance The integration of biomaterials science, innovative imaging, and cancer biology now enables the design of smart responsive material platforms for cancer theranostics. We show herein that our developed nanovehicle is able to sense and silence a multidrug resistance gene based on its expression in the tumor microenvironment, followed by local chemotherapeutic drug release, with a significant tumor regression not achieved otherwise. This ON/OFF molecular nanoswitch approach can be used to reverse the resistance to many other chemotherapeutic drugs and can serve as a universal gene therapy and drug delivery vehicle for cancer therapy. This disease-responsive platform can revolutionize clinical outcome and cancer patients’ point of care.
Nuria Oliva, Maria Carcole, Margarita Beckerman, Sivan Seliktar, Alison Hayward, James Stanley, Nicola Maria Anne Parry, Elazer R. Edelman, and Natalie Artzi
American Association for the Advancement of Science (AAAS)
Disease type and severity spur specific tissue alterations that can guide formulation of an optimal material for a selected clinical condition.
Nathaly Segovia, Maria Pont, Nuria Oliva, Victor Ramos, Salvador Borrós, and Natalie Artzi
Wiley
Of all the much hyped and pricy cancer drugs, the benefits from the promising siRNA small molecule drugs are limited. Lack of efficient delivery vehicles that would release the drug locally, protect it from degradation, and ensure high transfection efficiency, precludes it from fulfilling its full potential. This work presents a novel platform for local and sustained delivery of siRNA with high transfection efficiencies both in vitro and in vivo in a breast cancer mice model. siRNA protection and high transfection efficiency are enabled by their encapsulation in oligopeptide‐terminated poly(β‐aminoester) (pBAE) nanoparticles. Sustained delivery of the siRNA is achieved by the enhanced stability of the nanoparticles when embedded in a hydrogel scaffold based on polyamidoamine (PAMAM) dendrimer cross‐linked with dextran aldehyde. The combination of oligopeptide‐terminated pBAE polymers and biodegradable hydrogels shows improved transfection efficiency in vivo even when compared with the most potent commercially available transfection reagents. These results highlight the advantage of using composite materials for successful delivery of these highly promising small molecules to combat cancer.
Nuria Oliva, Sagi Shitreet, Eytan Abraham, Butch Stanley, Elazer R. Edelman, and Natalie Artzi
American Chemical Society (ACS)
We designed and optimized tissue-responsive adhesive materials by matching material and tissue properties. A two-component material based on dextran aldehyde and dendrimer amine provides a cohesive gel through aldehyde-amine cross-linking and an adhesive interface created by a dextran aldehyde-selective reaction with tissue amines. By altering aldehyde-amine chemistry, we examined how variations in tissue surfaces (serosal amine density in the duodenum, jejunum, and ileum) affect interactions with adhesive materials of varied compositions (aldehyde content). Interestingly, the same adhesive formulation reacts differentially with the three regions of the small intestine as a result of variation in the tissue amine density along the intestinal tract, affecting the tissue-material interfacial morphology, adhesion strength, and adhesive mechanical properties. Whereas tissues provide chemical anchors for interaction with materials, we were able to tune the adhesion strength for each section of the small intestine tissue by altering the adhesive formulation using a two-component material with flexible variables aimed at controlling the aldehyde/amine ratio. This tissue-specific approach should be applied to the broad spectrum of biomaterials, taking into account specific microenvironmental conditions in material design.
Natalie Artzi, Nuria Oliva, Cristina Puron, Sagi Shitreet, Shay Artzi, Adriana bon Ramos, Adam Groothuis, Gary Sahagian, and Elazer R. Edelman
Springer Science and Business Media LLC
Natalie Artzi, Nuria Oliva, Cristina Puron, Sagi Shitreet, Shay Artzi, Adriana bon Ramos, Adam Groothuis, Gary Sahagian, and Elazer R. Edelman
Springer Science and Business Media LLC