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Alessandro Grattoni

Alessandro Grattoni
Houston Methodist Research Institute, Houston, Texas · Nanomedicine

Ph.D.

About

118
Publications
13,328
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2,320
Citations
Introduction
Alessandro Grattoni obtained his Ph.D. degree in Biomedical Engineering in 2009 in Politecnico di Torino, Turin, Italy. He joined Houston Methodist Research Institute (Houston, Texas, USA) as an Assistant Professor in the Department of Nanomedicine in 2010. He holds the position of Chairman of the Department of Nanomedicine since 2015. He is currently a Professor in the Department of Nanomedicine at Houston Methodist Research Institute, and the Department of Surgery and Department of Radiation Oncology at Houston Methodist Hospital. His research focuses on implantable nanofluidics-based platforms for controlled and long-term drug delivery and cell transplantation.

Publications

Publications (118)
Article
Full-text available
Local immunomodulation has shown the potential to control the immune response in a site-specific manner for wound healing, cancer, allergy, and cell transplantation, thus abrogating adverse effects associated with systemic administration of immunotherapeutics. Localized immunomodulation requires confining the biodistribution of immunotherapeutics o...
Article
Molecular transport in nanofluidic systems exhibits properties that are unique to the nanoscale. Here, the electrostatic and steric interactions between particle and surfaces become dominant in determining particle transport. At the solid-liquid interface of charged surfaces an electric double layer (EDL) forms due to electrostatic interactions bet...
Article
Introduction: Cell transplantation is a promising curative therapeutic strategy whereby impaired organ functions can be restored without the need for whole organ transplantation. A key challenge in allotransplantation is the requirement for life-long systemic immunosuppression to prevent rejection, which is associated with serious adverse effects...
Preprint
Full-text available
Houston Methodist Research Institute https://orcid.org/0000-0001-7888-422X Article Abstract Pancreatic islet transplantation efficacy for type 1 diabetes (T1D) management is limited by hypoxia-related graft attrition and need for systemic immunosuppression. To overcome these challenges, we developed the Neovascularized Implantable Cell Homing and E...
Article
Full-text available
Mitigating the foreign body response (FBR) to implantable medical devices (IMDs) is critical for successful long‐term clinical deployment. The FBR is an inevitable immunological reaction to IMDs, resulting in inflammation and subsequent fibrotic encapsulation. Excessive fibrosis may impair IMDs function, eventually necessitating retrieval or replac...
Article
Full-text available
Cancer vaccines harness the host immune system to generate antigen-specific antitumor immunity for long-term tumor elimination with durable immunomodulation. Commonly investigated strategies reintroduce ex vivo autologous dendritic cells (DCs) but have limited clinical adoption due to difficulty in manufacturing, delivery and low clinical efficacy....
Article
Long-acting (LA) implantable drug delivery systems (IDDS) offer an effective approach for the management or prevention of chronic conditions by sustained parenteral therapeutic administration. LA IDDS can and improve adherence to treatment regimens by minimizing dosing frequency. However, their clinical deployment is challenged by factors such as,...
Article
Beta cell replacement has emerged as an attractive therapeutic alternative to traditional exogenous insulin administration for management of type 1 diabetes (T1D). Beta cells deliver insulin dynamically based on individual glycometabolic requirements, providing glycemic control while significantly reducing patient burden. Although transplantation i...
Article
Landmark successes in oncoimmunology have led to development of therapeutics boosting the host immune system to eradicate local and distant tumors with impactful tumor reduction in a subset of patients. However, current immunotherapy modalities often demonstrate limited success when involving immunologically cold tumors and solid tumors. Here, we d...
Article
Full-text available
Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular biomolecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabilize a colloidal solution and result in undesired m...
Preprint
Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular bio-molecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabilize a colloidal solution and result in undesired...
Article
Full-text available
Manipulation of ions and molecules by external control at the nanoscale is highly relevant to biomedical applications. We report a biocompatible electrode-embedded nanofluidic channel membrane designed for electrofluidic applications such as ionic field-effect transistors for implantable drug-delivery systems. Our nanofluidic membrane includes a po...
Conference Paper
Nanomedicine's inability to penetrate throughout an entire tumor volume, resulting from heterogeneous distribution within the tumor mass, remains a crucial limiting factor for a vast range of theranostic applications. Despite innumerable studies conducted on the topic that have shown efficacy and biocompatibility of colloidal gold nanoparticles (GN...
Article
Hypertension is a chronic condition that requires lifelong therapeutic management. Strict adherence to drug administration timing improves efficacy, while poor adherence leads to safety concerns. In light of these challenges, we present a nanofluidic technology that enables long-acting drug delivery with tunable timing of drug administration using...
Article
Full-text available
The ability to successfully develop a safe and effective vaccine for the prevention of HIV infection has proven challenging. Consequently, alternative approaches to HIV infection prevention have been pursued, and there have been a number of successes with differing levels of efficacy. Currently, only two oral pre-exposure prophylaxis (PrEP) product...
Article
In article number 2000163, Alessandro Grattoni and colleagues perform the first ever HIV preventive efficacy study using a subcutaneous drug delivery implant. The implant uses a nanofluidic membrane to sustainably deliver tenofovir alafenamide fumarate (TAF), a HIV antiretroviral, without pumps or actuation. Long‐term sustained TAF release, control...
Article
Full-text available
The heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity, as well as the clinical transla...
Article
Carbon fibers reinforced polymers (CFRPs) are prolifically finding applications in the medical field, moving beyond the aerospace and automotive industries. Owing to its high strength-to-weight ratio, lightness and radiolucency, CFRP-based materials are emerging to replace traditional metal-based medical implants. Numerous types of polymers matrice...
Conference Paper
In this work we present computational model for intraocular drug transport using coupled convective-diffusive equations. Model can simulate drug transport using either injection or by state of the art implant devices. We are using Navier-Stokes equation for fluid flow in vitreous humor, and composite smeared finite element (CSFE) for convection in...
Preprint
Heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity as well as the clinical translation...
Article
Full-text available
Pre‐exposure prophylaxis (PrEP) using antiretroviral oral drugs is effective at preventing human immunodeficiency virus (HIV) transmission when individuals adhere to the dosing regimen. Tenofovir alafenamide (TAF) is a potent antiretroviral drug, with numerous long‐acting (LA) delivery systems under development to improve PrEP adherence. However, n...
Conference Paper
Full-text available
Nanomedicines’ inability to penetrate throughout the entire volume of a tumor due to heterogeneous distribution within the tumor mass remains a crucial limiting factor for a vast range of theranostic applications, including image-guided radiation therapy. Despite many studies conducted on the topic having shown the efficacy and biocompatibility of...
Article
Full-text available
Background Pancreatic adenocarcinoma (PDAC) is associated with extremely poor prognosis and a 5-year survival rate of 10% and remains a lethal malignancy. Surgical resection and combination with chemoradiotherapy are the current standard-of-care options, may improve long-term survival in localized disease; however, the majority of patients are diag...
Article
Full-text available
Background Personalized therapeutic cancer vaccines aim to target and reprogram the host immune system to achieve cancer eradication in situ. Cancer vaccines deliver two main components: immunostimulants (iS) and tumor antigens to reduce tumor burden with a robust T cell response; however, none have reached broad clinical success due to difficulty...
Conference Paper
Lung cancer produces the highest number of cancer-related deaths worldwide. Currently, Non-Small Cell Lung Cancer (NSCLC) accounts for more than 85% of those cases. To date, achieving an early and precise diagnosis of NSCLC remains challenging due to extensive intratumor heterogeneity, which concerns not only to tumor epithelial cells but also the...
Article
Full-text available
HIV-1 is a chronic disease managed by strictly adhering to daily antiretroviral therapy (ART). However, not all people living with HIV-1 have access to ART, and those with access may not adhere to treatment regimens increasing viral load and disease progression. Here, a subcutaneous nanofluidic implant was used as a long-acting (LA) drug delivery p...
Article
In article number 2000670 by Alessandro Grattoni and co‐workers, vascularization of a subcutaneously implantable cell encapsulation platform is enhanced via enrichment with plateletrich plasma (PRP) and mesenchymal stem cells (MSCs) in rats and non‐human primates. Timepoint vascularity assessment demonstrates enrichment with PRP and MSCs increases...
Article
The current standard for cell encapsulation platforms is enveloping cells in semipermeable membranes that physically isolate transplanted cells from the host while allowing for oxygen and nutrient diffusion. However, long‐term viability and function of encapsulated cells are compromised by insufficient oxygen and nutrient supply to the graft. To ad...
Article
Full-text available
It has been suggested that particle size plays an important role in determining the genotoxicity of gold nanoparticles (GNPs). The purpose of this study was to compare the potential radio-sensitization effects of two different sized GNPs (3.9 and 37.4 nm) fabricated and examined in vitro in Lewis lung carcinoma (LLC) as a model of non-small cell lu...
Article
Purpose Mounting evidence demonstrates that combining radiotherapy (RT) with immunotherapy can reduce tumor burden in a subset of patients. However, conventional systemic delivery of immunotherapeutics is often associated with significant adverse effects, which force treatment cessation. The aim of this study is to investigate a minimally invasive...
Conference Paper
Full-text available
This study aims to evaluate the in vivo distribution of Gold Nanoparticles (GNPs) at different time points after intratumoral (IT) injection, exploiting their properties as contrast agents for Computed Tomography (CT). GNPs approximately 40 nm in diameter were synthesized with a surface plasmon peak at ~530 nm, capped with Bovine Serum Albumin (BSA...
Preprint
It has been suggested that particle size plays an important role in determining the genotoxicity of gold nanoparticles (GNPs). The purpose of this study was to compare the potential radio-sensitization effects of two different sized GNPs (3.9 and 37.4 nm) fabricated and examined in vitro in Lewis Lung carcinoma (LLC) as a model of non-small cell lu...
Article
Full-text available
Cell encapsulation is an attractive transplantation strategy to treat endocrine disorders. Transplanted cells offer a dynamic and stimulus-responsive system that secretes therapeutics based on patient need. Despite significant advancements, a challenge in allogeneic cell encapsulation is maintaining sufficient oxygen and nutrient exchange, while pr...
Article
Full-text available
Individualized long-term management of chronic pathologies remains an elusive goal despite recent progress in drug formulation and implantable devices. The lack of advanced systems for therapeutic administration that can be controlled and tailored based on patient needs precludes optimal management of pathologies, such as diabetes, hypertension, rh...
Article
Tumor uptake and biodistribution of immunotherapy is associated with clinical response as well as toxicity. To augment immunotherapy bioavailability in the tumor, an intratumoral administration route via direct injection or local release technologies has emerged as an appealing approach. Here the biodistribution of an agonistic anti‐CD40 monocolona...
Article
Full-text available
In article number 2000014 Alessandro Grattoni and co‐workers present the first‐ever in vivo study of an implantable drug delivery device in microgravity aboard the International Space Station. In this unprecedented research endeavor, the muscle hypertrophic effect of nanofluidic‐mediated sustained low dose elution of formoterol is demonstrated in r...
Article
Long-acting (LA) pre-exposure prophylaxis (PrEP) for HIV prevention is poised to address non-adherence and implementation challenges by alleviating the burden of user-dependent dosing. Due to its potency, tenofovir alafenamide (TAF) is a viable candidate for LA PrEP. However, the inherent hydrolytic instability of TAF presents a challenge for appli...
Article
The fundamental limitations of systemic therapeutic administration have prompted the development of local drug delivery platforms as a solution to increase effectiveness and reduce side effects. By confining therapeutics to the site of disease, local delivery technologies can enhance therapeutic index. This review highlights recent advances and opp...
Preprint
Full-text available
Pre-exposure prophylaxis (PrEP) using antiretroviral oral drugs is effective at preventing HIV transmission when individuals adhere to the dosing regimen. Tenofovir alafenamide (TAF) is a potent antiretroviral drug, with numerous long-acting (LA) delivery systems under development to improve PrEP adherence. However, none has undergone preventive ef...
Article
Full-text available
Skeletal muscle atrophy is a critical health problem that affects quality of life and increases morbidity and mortality. At present, exercise training remains the only intervention and pharmaceutical treatments remain elusive. Formoterol (FMT), a β2‐adrenergic receptor agonist, has emerged as a potential therapeutic by triggering skeletal muscle an...
Article
Full-text available
Patient-centered therapeutic management for chronic medical conditions is a desired but unmet need, largely attributable to the lack of adequate technologies for tailored drug administration. While triggered devices that control the delivery of therapeutics exist, they often rely on impractical continuous external activation. As such, next generati...
Article
Molecular transport through nanofluidic structures exhibits properties that are unique at the nanoscale. The high surface-to-volume ratio of nanometer-sized confined spaces renders particle interactions with the surface of central importance. The electrical double layer (EDL) at the solid-liquid interface of charged surfaces, generates an enrichmen...
Article
Full-text available
Chronic diseases such as hypertension and rheumatoid arthritis are persistent ailments that require personalized lifelong therapeutic management. However, the difficulty of adherence to strict dosing schedule compromises therapeutic efficacy and safety. Moreover, the conventional one-size-fits-all treatment approach is increasingly challenged due t...
Article
Chronic diseases account for the majority of all deaths worldwide, and their prevalence is expected to escalate in the next 10 years. Because chronic disorders require long-term therapy, the healthcare system must address the needs of an increasing number of patients. The use of new drug administration routes, specifically implantable drug delivery...
Article
Preexposure prophylaxis (PrEP) with antiretrovirals (ARV) can prevent human immunodeficiency virus (HIV) transmission, but its efficacy is highly dependent on strict patient adherence to daily dosing regimen. Long- acting (LA) ARV formulations or delivery systems that reduce dosing frequency may increase adherence and thus PrEP efficacy. While cabo...
Article
37 Background: Immune related adverse events still occur in up to 91% of patients receiving immunotherapy. Intratumoral administration is a potential solution to limit these events by reducing systemic exposure while increasing local concentration. However, intratumoral injection is hindered by rapid clearance of drug from the tumor. Our group has...
Article
The pericardium, which surrounds the heart, provides a unique enclosed volume and a site for the delivery of agents to the heart and coronary arteries. While strategies for targeting the delivery of therapeutics to the heart are lacking, various technologies and nanodelivery approaches are emerging as promising methods for site specific delivery to...
Article
Globally, 145.2 million people suffer from moderate to severe vision impairment or blindness due to preventable or treatable causes. However, patient adherence to topical or intravitreal treatment is a leading cause of poor outcomes. To address this issue, we designed an intraocularly implantable device called the nanofluidic Vitreal System for The...
Article
Gas transport across nanoscale pores is determinant in molecular exchange in living organisms as well as in a broad spectrum of technologies. Here we report an unprecedented theoretical and experimental analysis of gas transport in a consistent set of confining nanochannels ranging in size from the ultra-nano- to the sub-microscale. A generally app...
Article
Pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) drugs are effective at preventing human immunodeficiency virus (HIV) transmission. However, implementation of PrEP presents significant challenges due to poor user adherence, low accessibility to ARVs and multiple routes of HIV exposure. To address these challenges, we developed the nanochan...
Article
Conventional systemic immunotherapy administration often results in insufficient anti-tumor immune response and adverse side effects. Delivering immunotherapeutics intratumorally could maximize tumor exposure, elicit efficient anti-tumor immune response, and minimize toxicity. To fulfill the unmet clinical need for sustained local drug delivery and...
Article
Conventional systemic immunotherapy administration often results in insufficient anti-tumor immune response and adverse side effects. Delivering immunotherapeutics intratumorally could maximize tumor exposure, elicit robust anti-tumor immune response, and minimize toxicity. To fulfill the unmet clinical need for sustained local drug delivery and to...
Article
Full-text available
With nearly 40% of U.S. adults obese, and childhood and adolescent rates rising, obesity and associated comorbidities are serious public health concerns with massive societal costs. Often, lifestyle interventions do not offer sufficient weight loss to improve health, requiring surgery and medications as adjunct management strategies. Here, we prese...
Article
Autologous cell transplantation holds enormous promise to restore organ and tissue functions in the treatment of various pathologies including endocrine, cardiovascular, and neurological diseases among others. Even though immune rejection is circumvented with autologous transplantation, clinical adoption remains limited due to poor cell retention a...
Article
Full-text available
Ionic transport through nanofluidic systems is a problem of fundamental interest in transport physics and has broad relevance in desalination, fuel cells, batteries, filtration, and drug delivery. When the dimension of the fluidic system approaches the size of molecules in solution, fluid properties are not homogeneous and a departure in behavior i...
Patent
A method for the fail - safe termination of in vivo drug delivery from an implantable drug delivery system , the method comprising : providing an implantable drug delivery system comprising : a housing having a reservoir for containing a drug , and a port for dispensing the drug to a patient; and an emergency deactivation unit disposed between the...
Article
Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells,...
Article
Cell-based therapy is emerging as a promising strategy for treating a wide range of human diseases, such as diabetes, blood disorders, acute liver failure, spinal cord injury, and several types of cancer. Pancreatic islets, blood cells, hepatocytes, and stem cells are among the many cell types currently used for this strategy. The encapsulation of...
Article
Cell transplantation in bioengineered scaffolds and encapsulation systems has shown great promise in regenerative medicine. Depending on the site of implantation, type of cells and their expected function, these systems are designed to provide cells with a physiological-like environment while providing mechanical support and promoting long-term via...
Article
Hydroxypropyl-β-cyclodextrin (HP-β-CyD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CyD) were used to generate hydrophilic complexes of the poorly water-soluble drug testosterone propionate (TP). The inclusion complexes were obtained by freeze-drying, and then analyzed at both liquid and solid states. Phase solubility studies, performed according to...
Article
Transplantation of pancreatic islets or stem cell derived insulin secreting cells is an attractive treatment strategy for diabetes. However, islet transplantation is associated with several challenges including function-loss associated with dispersion and limited vascularization as well as the need for continuous immunosuppression. To overcome thes...
Article
Full-text available
In numerous pathologies, implantable drug delivery devices provide advantages over conventional oral or parenteral approaches. Based on the site of implantation and release characteristics, implants can afford either systemic delivery or local administration, whereby the drug is delivered at or near the site of intended action. Unfortunately, curre...
Article
This study demonstrated a nanochannel membrane device (NMD) for controlled and sustained release of GC-1 in rats, in the context of the treatment of metabolic syndrome. Release profiles were established in vitro both with and without 5% labrasol for over 2 months. In vivo pharmacokinetic evaluation showed effective GC-1 plasma concentrations, which...
Article
Nanofluidic implantables represent a recent advance in a broad effort for developing personalized, point-of-care medical technologies. Such systems have unprecedented potential when matched with the newest developments in robotics, microprocessing, and tissue engineering. In this review, we present their emergence in medicine within the fields of d...