Roberto Palomba

Istituto Italiano di Tecnologia | IIT · Department of Drug Discovery and Development

The storied history of controlled the release systems has evolved over time; from degradable drug-loaded sutures to monolithic zero-ordered release devices and nano-sized drug delivery formulations. Scientists have tuned the physico-chemical properties of these drug carriers to optimize their performance in biomedical/pharmaceutical applications. I...

The storied history of controlled the release systems has evolved over time; from degradable drug-loaded sutures to monolithic zero-ordered release devices and nano-sized drug delivery formulations. Scientists have tuned the physico-chemical properties of these drug carriers to optimize their performance in biomedical/pharmaceutical applications. I...

Surface PEGylation, biological camouflage, shape and stiffness modulation of nanoparticles as well as liver blockade and macrophage depletion have all improved the blood longevity of nanomedicines. Yet, the mononuclear phagocytic system still recognizes, sequesters, and processes the majority of blood borne particles. Here, the natural fatty acid m...

In the tumor microenvironment, mesenchymal stromal cells (MSCs) are key modulators of cancer cell behavior in response to several stimuli. Intratumoral acidosis is a metabolic trait of fast-growing tumors that can induce a pro-tumorigenic phenotype in MSCs through the activation of the NF-κB-mediated inflammatory pathway, driving tumor clonogenicit...

Methotrexate (MTX), a compound originally used as an anticancer drug, has also found applications in a broad variety of autoimmune disorders thanks to its anti-inflammation and immunomodulatory functions. The broad application of MTX is anyway limited by its poor solubility in biological fluids, its poor bioavailability and its toxicity. In additio...

Abstract Ionizable lipid nanoparticles (LNPs) are the most clinically advanced nano‐delivery system for therapeutic nucleic acids. The great effort put in the development of ionizable lipids with increased in vivo potency brought LNPs from the laboratory benches to the FDA approval of patisiran in 2018 and to the ongoing clinical trials for mRNA‐ba...

Macrophage inflammation and maturation into foam cells, following the engulfment of oxidized low-density lipoproteins (oxLDL), are major hallmarks in the onset and progression of atherosclerosis. Yet, chronic treatments with anti-inflammatory agents, such as methotrexate (MTX), failed to modulate disease progression, possibly for the limited drug b...

Despite recent advances in drug delivery, the targeted treatment of unhealthy cells or tissues continues to remain a priority. In cancer (much like other pathologies), delivery vectors are designed to exploit physical and biological features of unhealthy tissues that are not always homogenous across the disease. In some cases, shifting the target f...

The vascular transport of molecules, cells and nanoconstructs is a fundamental biophysical process impacting tissue regeneration; delivery of nutrients and therapeutic agents; and the response of the immune system to external pathogens. This process is often studied in single-channel microfluidic devices lacking the complex tri-dimensional organiza...

Metastases are the primary cause of death in cancer patients. Small animal models are helping in dissecting some of key features in the metastatic cascade. Yet, tools for systematically analyze the contribution of blood flow, vascular permeability, inflammation, tissue architecture, and biochemical stimuli are missing. In this work, a microfluidic...

Metastases are the primary cause of death in cancer patients. Small animal models are helping in dissecting some of key features in the metastatic cascade. Yet, tools for systematically analyze the contribution of blood flow, vascular permeability, inflammation, tissue architecture, and biochemical stimuli are missing. In this work, a microfluidic...

Although a plethora of nanoparticle configurations have been proposed over the past 10 years, the uniform and deep penetration of systemically injected nanomedicines into the diseased tissue stays as a major biological barrier. Here, a ‘Tissue Chamber’ chip is designed and fabricated to study the extravascular transport of small molecules and nanop...

A variety of microparticles have been proposed for the sustained and localized delivery of drugs whit the objective of increasing therapeutic indexes by circumventing filtering organs and biological barriers. Yet, the geometrical, mechanical and therapeutic properties of such microparticles cannot be simultaneously and independently tailored during...

Tissue plasminogen activator (tPA) is the sole approved therapeutic molecule for the treatment of acute ischemic stroke. Yet, only a small percentage of patients could benefit from this life-saving treatment because of medical contraindications and severe side effects, including brain hemorrhage, associated with delayed administration. Here, a nano...

Atherosclerosis (AS) is a disorder of large and medium-sized arteries; it consists in the formation of lipid-rich plaques in the intima and inner media, whose pathophysiology is mostly driven by inflammation. Currently available interventions and therapies for treating atherosclerosis are not always completely effective; side effects associated wit...

Tissue plasminogen activator (tPA) is the sole approved therapeutic molecule for the treatment of acute ischemic stroke. Yet, only a small percentage of patients could benefit from this life-saving treatment because of medical contraindications and severe side effects, including brain hemorrhage, associated with delayed administration. Here, a nano...

A variety of microparticles have been proposed for the sustained and localized delivery of drugs whit the objective of increasing therapeutic indexes by circumventing filtering organs and biological barriers. Yet, the geometrical, mechanical and therapeutic properties of such microparticles cannot be simultaneously and independently tailored during...

The effect of nanoparticle size, shape and surface properties on cellular uptake has been extensively investigated for its basic science and translational implications. Recently, softness is emerging as a design parameter for modulating the interaction of nanoparticles with cells and the biological microenvironment. Here, circular, quadrangular and...

Inflammation is a common hallmark in several diseases, including atherosclerosis, cancer, obesity, and neurodegeneration. In Alzheimer’s disease (AD), growing evidence directly correlates neuronal damage with inflammation of myeloid brain cells, such as microglia. Here, polymeric nanoparticles were engineered and characterized for the delivery of a...

The innate immune system provides the first line of defence against foreign microbes and particulate materials. Engineered nanoparticles can interact with the immune system in many different ways. Nanoparticles may thus elicit inflammation with engagement of neutrophils, macrophages and other effector cells; however, it is important to distinguish...

Over the last 15 years, a plethora of materials and different formulations have been proposed for the realization of nanomedicines. Yet drug-loading efficiency, sequestration by phagocytic cells, and tumor accumulation are sub-optimal. This would imply that radically new design approaches are needed to propel the clinical integration of nanomedicin...

Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, loca...

The ability of nanoparticles to evade the immune system, cross biological barriers, and localize at the target tissue ultimately determines their therapeutic potential. Leukocytes naturally encompass all of these features and, therefore, provide great inspiration in biomimetic vectors. Herein, we present a hybrid drug delivery system, termed leukol...

The use of a monoclonal antibody to block the neurite outgrowth inhibitor Nogo-A has been of great interest for promoting axonal recovery as a treatment for spinal cord injury. While several cellular and non-cellular assays have been developed to quantify the bioactive effects of Nogo-A signaling, demand still exists for the development of a reliab...

A key step in particle-based drug delivery through microcirculation is particle migration from blood flow to vessel walls, also known as "margination", which promotes particle contact and adhesion to the vesselwall. Margination and adhesion should be independently addressed as two distinct phenomena, considering that the former is a fundamental pre...

Introduction We showed that nanoporous silicon (NPS) particles coated with leukocyte cellular membranes -Leukolike Vectors (LLV) - possess cell-like properties. These biomimetic carriers can escape macrophage uptake, delay sequestration by the reticulo-endothelial system, target tumor inflamed vasculature and accumulate within the cancer parenchyma...

Nanocarriers are designed to specifically accumulate in diseased tissues. In this context, targeting of intracellular compartments was shown to enhance the efficacy of many drugs and to offer new and more effective therapeutic approaches. This is especially true for therapies based on biologicals that must be encapsulated to favor cell internalizat...

Tumor extracellular matrix (ECM) represents a major obstacle to the diffusion of therapeutics and drug delivery systems in cancer parenchyma. This biological barrier limits the efficacy of promising therapeutic approaches including the delivery of siRNA or agents intended for thermoablation. After extravasation due to the enhanced penetration and r...