Nanbiosis

New Consequences in Familial Hypercholesterolemia due to Abnormal LDL

Misfolded ApoB100 in LDL promotes plaque buildup in familial hypercholesterolemia, raising cardiovascular risk. Structural preservation may aid prevention.

Barcelona, febrero 2025. As recently published in the ICMAB webpage, a new study links ApoB100 protein structure (a key protein found in low-density lipoprotein, LDL, often called “bad cholesterol”) to increased cardiovascular risk in familial hypercholesterolemia. The study, led by IIBB-CSIC and CIBER, with the contribution of ICMAB’s SOFT Service (with NANBIOSIS Unit 6 at its core), shows that the protein structure directly contributes to an increased tendency to aggregate and form atherosclerotic plaques in patients with familial hypercholesterolemia.

In these patients, LDL particles are smaller due to their high content of esterified cholesterol, and ApoB100 has a less flexible structure due to its high percentage of rigid alpha-helices. Developing strategies to preserve the structure of ApoB100 could be a new way to reduce the risk of cardiovascular disease in these patients.

ApoB100 protein structure drives LDL accumulation and increases cardiovascular risk, study finds

This new multicenter study reveals why the structure of the ApoB100 protein, present in LDL along with the so-called “bad cholesterol,” plays a crucial role in the tendency of LDL to accumulate in the arterial walls of patients with familial hypercholesterolemia, thus promoting the formation of atherosclerotic plaques.

The study is led by Vicenta Llorente Cortes, a researcher at the Biomedical Research Institute of Barcelona (IIBB-CSIC) and CIBER-CV, and Valerie Samouillan, a researcher at the University of Toulouse Paul Sabatier.

Familial hypercholesterolemia is a fairly common genetic disorder, affecting about 1 in every 200 or 300 people. Those affected have high levels of low-density lipoprotein (LDL) cholesterol from birth and consequently have a higher risk of cardiovascular diseases and greater rates of premature death due to these conditions.

But, why do LDL particles aggregate more in these individuals? Are there biochemical and physical differences that explain this? This is what the study, published a few weeks ago in the Journal of Lipid Research, aimed to clarify. The study involved 10 research centers in Spain and France. These include, in addition to IIBB-CSIC and CIBER, the Institute of Materials Science of Barcelona (ICMAB-CSIC), the Sant Pau Research Institute (IR Sant Pau), the Autonomous University of Barcelona (UAB), the CIRIMAT Institute (Toulouse, France), and the Miquel Servet Hospital in Zaragoza.

ApoB100 Structure: Less flexible in small, dense LDL particles in patients with familial hypercholesterolemia

LDL particles in patients with familial hypercholesterolemia show a greater tendency to aggregate and form plaques. This is due, explains Vicenta Llorente Cortes, “to the fact that the ApoB100 protein in LDL has a particular structural conformation, with a high percentage of rigid alpha-helices [secondary structures], compared to LDL from healthy patients.”

Using samples from 35 patients with familial hypercholesterolemia and 29 healthy individuals as a control group, the researchers demonstrated that in patients with familial hypercholesterolemia, the protein present in LDL is smaller due to its high content of esterified cholesterol and has less structural flexibility compared to LDL from healthy individuals. As a result, these LDL particles have a lower ability to recover their structure at the arterial intima, promoting their accumulation on the inner walls of the arteries.

Various Techniques to Study LDL Particles

The study measured, among other things, the ease with which LDL particles aggregate using dynamic light scattering techniques (measured at the SOFT Service at ICMAB-CSIC, Unit 6 of NANBIOSIS), as well as the size, composition, and structure of LDL particles through electron microscopy.

As Llorente explains, one of the most impactful findings was the discovery of the difference in the percentage of flexible secondary structures in ApoB100 from patients with familial hypercholesterolemia, which would not have been possible without the collaboration of the biophysics group led by Valerie Samouillan (University of Toulouse). This group applied the FTIR infrared spectroscopy technique to determine the protein’s structure and, in particular, quantify the stable alpha-helices and flexible alpha-helices in LDL from control and patient groups.

The results suggest that developing strategies to structurally preserve ApoB100, and in particular the percentage of flexible alpha-helices in LDL, could be a new way to reduce the risk of cardiovascular disease in patients.

This finding offers a new perspective on how alterations in ApoB100 structure can directly influence the risk of developing cardiovascular diseases. Furthermore, it opens possibilities for designing specific therapies aimed at modulating the content of flexible alpha-helices in LDL, contributing to the prevention of atherosclerosis.

“With these new peptide tools, we aim to preserve the structural flexibility of the ApoB100 protein in LDL from patients with familial hypercholesterolemia.”

Vicenta Llorente

“In our research group,” adds Vicenta Llorente, “we are comparing whether PCSK9 inhibitors [a type of drug] can help preserve the percentage of flexible alpha-helices and whether these effects are comparable to those achieved through innovative peptide tools developed in our group specifically for this purpose. With these new peptide tools, we aim to preserve the structural flexibility of the ApoB100 protein in LDL from patients with familial hypercholesterolemia.”

ICMAB and NANBIOSIS contribution

Amable Bernabé, technician at the SOFT Service of ICMAB-CSIC, and part of NANBIOSIS (Unit 6), played a key role in this study, contributing to the analysis of LDL particle size using the dynamic light scattering (DLS) (Zetasizer) technique. He also participated in the development of the analysis method, interpreting the results, discussing them, and proposing complementary techniques to make the study more robust.

The SOFT Service offers state-of-the-art equipment and technical support for the preparation and characterization of micro- and nanostructured soft molecular materials. This includes molecular surfaces, micro- and nanoparticulate materials, plastic films, dispersed systems, and self-assembled monolayers (SAMs). These materials have applications across various fields, including biomedicine, electronics, energy storage, and other chemical and materials sciences.

Reference article:

Maria Teresa La Chica Lhoëst, Andrea Martínez, Eduardo Garcia, Jany Dandurand, Anna Polishchuk, Aleyda Benitez-Amaro, Ana Cenarro, Fernando Civeira, Amable Bernabé, David Vilades, Joan Carles Escolà-Gil, Valerie Samouillan, Vicenta Llorente-Cortes.
ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients.
Journal of Lipid Research. 2025 Jan;66(1):100703. DOI: 10.1016/j.jlr.2024.100703

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More information about the publication can be found here. This article is a reproduction with a slight edition that does not alter the overall message.

What is NANBIOSIS?

The goal of NANBIOSIS is to provide comprehensive and integrated advanced solutions for companies and research institutions in biomedical applications. All of this is done through a single-entry point, involving the design and production of biomaterials, nanomaterials, and their nanoconjugates. This includes their characterization from physical-chemical, functional, toxicological, and biological perspectives (preclinical validation).

Leading scientists

The main value of NANBIOSIS is our highly qualified and experienced academic scientists, working in public institutions, renowned universities and other research institutes.

Custom solutions

Designed for either scientific collaboration or the private industry, we adapt our services to your needs, filling the gaps and paving the way towards the next breakthrough.

Cutting-Edge facilities

Publicly funded, with the most advanced equipment, offering a wide variety of services from synthesis of nanoparticles and medical devices, including up to preclinical trials.

Standards of quality

Our services have standards of quality required in the pharmaceutical, biotech and medtech sectors, from Good Practices to ISO certifications.

In order to access our Cutting-Edge Biomedical Solutions with priority access, enter our Competitive Call here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

New Pancreatic Cancer Treatment: Hyperthermic Therapy with Magnetic Nanoparticles

Vall d’Hebron develops magnetic nanoparticle hyperthermia to enhance pancreatic cancer treatment, now advancing to clinical trials.

Barcelona, january 2025. A clinical trial targeting patients with locally advanced pancreatic cancer has been approved following a study led by the Vall d’Hebron Research Institute (VHIR).

A preclinical study led by the Clinical Biochemistry, Drug Targeting, and Therapy (CB-DDT) group at Vall d’Hebron Research Institute (VHIR), which Unit 20 of NANBIOSIS is integrated, has proposed the use of magnetic nanoparticles and hyperthermia to enhance the treatment of pancreatic adenocarcinoma. The goal is to penetrate the desmoplastic stroma—the dense tissue surrounding these tumors—which acts as a barrier to chemotherapy. Overcoming this matrix to directly reach the tumor is crucial for improving the survival rate of pancreatic cancer patients, which currently stands at only 16% at five years.

The research, conducted in collaboration with CIBER-BBN, one of the nodes of NANBIOSIS, and other national and international research centers, has been published in Applied Materials & Interfaces. Based on these promising results, a clinical trial led by the Vall d’Hebron Institute of Oncology (VHIO) has been initiated to assess this approach in patients with locally advanced pancreatic cancer.

A Multidisciplinary Approach in the NoCanTher Project

This investigation is part of the NoCanTher project, which brings together experts from eleven national and international institutions. Funded by the Horizon 2020 program, the NoCanTher consortium seeks innovative strategies against pancreatic adenocarcinoma by leveraging magnetic nanoparticles. It is estimated that 20% of pancreatic cancer patients have this specific pathology, characterized by tumors without metastasis but which cannot be surgically removed. Currently, the only available treatment option is palliative chemotherapy.

The project focuses on developing iron-based magnetic nanoparticles that, when exposed to an alternating magnetic field, generate heat (magnetic hyperthermia). This heat can be used to make the desmoplastic stroma more permeable, allowing chemotherapy to reach the malignant cells more effectively. The treatment’s efficacy is enhanced to the point where tumor cells can be destroyed.

Promising Results and Clinical Implications

The study demonstrates that when these nanoparticles are injected directly into the tumor, the hyperthermia they generate reduces tumor volume and induces physical changes that facilitate chemotherapy penetration. “This highlights a significant synergistic effect between nanoparticle-induced hyperthermia and chemotherapy in treating pancreatic cancer,” explains Dr. Simón Schwartz Jr, Director of Research and Innovation at the Department of Biochemistry and co-principal investigator of the project alongside Dr. Ibane Abasolo, currently a principal researcher at the Institute of Advanced Chemistry of Catalonia and the Scientific Director of Unit 20.

“This highlights a significant synergistic effect between nanoparticle-induced hyperthermia and chemotherapy in treating pancreatic cancer”

Dr. Simón Schwartz Jr

Beyond evaluating the treatment’s efficacy in humans, the researchers will also collect blood samples from trial participants to determine whether this therapy reduces the number of circulating tumor cells in the bloodstream, particularly cancer stem cells, which are responsible for generating new cancer cells and metastasizing. Although this remains a relatively new field of research, for cases where external beam radiotherapy poses a higher risk of toxicity, this innovative approach could offer a viable treatment alternative—especially for patients who do not respond to standard therapies.

More information about the publication can be found here.

What is NANBIOSIS?

The goal of NANBIOSIS is to provide comprehensive and integrated advanced solutions for companies and research institutions in biomedical applications. All of this is done through a single-entry point, involving the design and production of biomaterials, nanomaterials, and their nanoconjugates. This includes their characterization from physical-chemical, functional, toxicological, and biological perspectives (preclinical validation).

Leading scientists

The main value of NANBIOSIS is our highly qualified and experienced academic scientists, working in public institutions, renowned universities and other research institutes.

Custom solutions

Designed for either scientific collaboration or the private industry, we adapt our services to your needs, filling the gaps and paving the way towards the next breakthrough.

Cutting-Edge facilities

Publicly funded, with the most advanced equipment, offering a wide variety of services from synthesis of nanoparticles and medical devices, including up to preclinical trials.

Standards of quality

Our services have standards of quality required in the pharmaceutical, biotech and medtech sectors, from Good Practices to ISO certifications.

In order to access our Cutting-Edge Biomedical Solutions with priority access, enter our Competitive Call here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

A Breakthrough Therapy for Fabry Disease: nanoGLA Demonstrates Promising Results

Fabry disease therapy nanoGLA, developed by NANBIOSIS and our partners, shows superior efficacy in preclinical trials, targeting systemic and brain symptoms.

Barcelona, january 2025. An international research team led by the Institute of Materials Science of Barcelona (ICMAB-CSIC) and CIBER-BBN, in collaboration with the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), has developed a groundbreaking nanotechnology-based therapy called nanoGLA for the treatment of Fabry disease. The innovative solution has shown remarkable efficacy in preclinical studies and has been published in the open-access journal Science Advances (see below for reference links).

What is Fabry disease?

Fabry disease is a rare genetic disorder caused by a deficiency of the enzyme α-galactosidase A (GLA). This deficiency leads to the accumulation of fatty substrates (mainly globotriaosylceramide or Gb3) in cells, resulting in severe damage to various organs. The nanoGLA therapy employs peptide-guided nanoliposomes to deliver the deficient GLA enzyme effectively to the organs most affected by the disease. Researchers have successfully produced nanoGLA at the quality and scale required for preclinical trials, paving the way for clinical testing.

GLA inside nanoliposomes: nanoGLA

In studies with mouse models of Fabry disease, nanoGLA demonstrated superior efficacy compared to therapies using the non-encapsulated enzyme. It effectively targeted affected organs and, notably, the brain — a critical achievement that current therapies cannot match. These findings underscore nanoGLA’s potential to address both systemic and cerebrovascular manifestations of Fabry disease.

Highlighting the importance of this innovation, the European Medicines Agency (EMA) granted nanoGLA the Orphan Medicinal Product Designation in 2021, a significant milestone in its development.

The contribution of NANBIOSIS to this project was regarding the synthesis, processing and nanostructuring of the formulation (Unit 3 and Unit 6), and the preclinical assays using Fabry disease mouse models (Unit 20). Remember that if you want to collaborate with us, we are at the final stretch of our Open Call!

The product of scientific collaboration

This breakthrough is the result of collaborative efforts in which NANBIOSIS played a crucial role. These involve multiple international institutions, including ICMAB-CSIC, CIBER-BBN, Vall d’Hebron Research Institute (VHIR), and companies such as Nanomol Technologies SL and Leanbio SL, as well as IQAC-CSIC, the Institute of Biotechnology and Biomedicine (IBB-UAB), and international partners like Joanneum Research–Institute for Biomedical Research and Technologies (HEALTH) (Austria), Technion-Israel Institute of Technology (Israel), Guangdong-Technion Israel Institute of Technology (China), Aarhus University (Denmark), and Labcorp Drug Development (UK).

“The nanoGLA formulation represents a promising opportunity for Fabry disease patients, especially in addressing neurological symptoms, which current therapies fail to tackle.”

Elisabet González, ICMAB researcher and lead author

“The nanoGLA formulation represents a promising opportunity for Fabry disease patients, especially in addressing neurological symptoms, which current therapies fail to tackle,” said Elisabet González, researcher at ICMAB and one of the study’s lead authors. “Our goal is to develop safer and more effective treatments by harnessing the potential of nanotechnology.”

The bright future of this research

The research was conducted within the framework of the European project Smart4Fabry, funded by the European Union’s Horizon 2020 research and innovation program. Building on these promising results, the European Commission has provided further funding through the EU Phoenix and Nano4Rare projects to complete the preclinical phase and secure approval to begin clinical trials with human patients.

For more information, refer to the original study: “Targeted nanoliposomes to improve enzyme replacement therapy of Fabry disease,” published in Science Advances, Vol. 10, Issue 50, DOI: 10.1126/sciadv.adq4738.

This article was adapted from the press release by ICMAB. Press contact: communication@icmab.es. Institut de Ciència de Materials de Barcelona (ICMAB, CSIC).

What is NANBIOSIS?

The goal of NANBIOSIS is to provide comprehensive and integrated advanced solutions for companies and research institutions in biomedical applications. All of this is done through a single-entry point, involving the design and production of biomaterials, nanomaterials, and their nanoconjugates. This includes their characterization from physical-chemical, functional, toxicological, and biological perspectives (preclinical validation).

Leading scientists

The main value of NANBIOSIS is our highly qualified and experienced academic scientists, working in public institutions, renowned universities and other research institutes.

Custom solutions

Designed for either scientific collaboration or the private industry, we adapt our services to your needs, filling the gaps and paving the way towards the next breakthrough.

Cutting-Edge facilities

Publicly funded, with the most advanced equipment, offering a wide variety of services from synthesis of nanoparticles and medical devices, including up to preclinical trials.

Standards of quality

Our services have standards of quality required in the pharmaceutical, biotech and medtech sectors, from Good Practices to ISO certifications.

In order to access our Cutting-Edge Biomedical Solutions with priority access, enter our Competitive Call here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them: