An enhanced drug delivery system for brain cancer treatment which will be tested by human cell-based 3D in vitro microfluidic system

Project Information

Enhanced-DDS

Grant agreement ID: 101110722

DOI

10.3030/101110722

Project closed

EC signature date 27 April 2023

Start date 1 July 2023

End date 31 August 2025

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 148 478,40

Coordinated by

SABANCI UNIVERSITESI
Türkiye

Periodic Reporting for period 1 - Enhanced-DDS (An enhanced drug delivery system for brain cancer treatment which will be tested by human cell-based 3D in vitro microfluidic system)

Reporting period: 2023-07-01 to 2025-08-31

Summary of the context and overall objectives of the project

Brain cancer remains one of the most challenging diseases to treat, primarily due to the presence of the blood–brain barrier (BBB), a natural defense system that prevents most drugs from reaching the brain. Conventional chemotherapy often causes severe side effects and exhibits limited therapeutic efficacy because of poor drug delivery to brain tumors. In this context, nanotechnology-based drug delivery systems especially mesoporous silica nanoparticles (MSNs) have shown great promise for transporting drugs across biological barriers. However, current MSN synthesis methods rely heavily on toxic chemicals, are energy-intensive, and often lack sufficient biocompatibility for clinical translation.
This project addresses these challenges by developing an eco-friendly, cost-effective, and biocompatible nanocarrier system for brain cancer treatment. The project introduces an innovative approach to synthesizing MSNs entirely from natural biosources such as rice husk and horsetail, integrating green chemistry principles with advanced plasma surface modification techniques to enhance nanoparticle performance. These biosilica-based nanoparticles will then be tested in a human cell–based 3D microfluidic model of brain cancer, a next-generation in vitro platform that mimics physiological conditions and reduces dependence on animal models.
The project has three interlinked objectives:
1. Identify the best natural source of silica for MSN production using green extraction methods to ensure high purity, sustainability, and economic viability.
2. Modify the MSN surface to improve stability, targeting efficiency, and biocompatibility without relying on toxic reagents.
3. Evaluate the therapeutic efficacy of the designed nanoparticles in a 3D microfluidic brain tumor model, combining nanotechnology with modern tissue-engineering techniques to simulate the tumor microenvironment.
By bridging materials science, biomedical engineering, and nanomedicine, the project aims to pioneer a new class of biogenic and engineered nanocarriers for brain-targeted drug delivery. This interdisciplinary research responds directly to global and European priorities in sustainable healthcare, green innovation, and the reduction of animal testing, aligning with the European Green Deal and EU’s Horizon Europe missions on cancer and health.
Beyond scientific outcomes, the project has strong societal and economic implications. It promotes environmentally sustainable nanotechnology, contributes to circular economy principles by valorizing agricultural waste, and supports the transition toward animal-free drug testing through the development of advanced 3D in vitro models. Economically, the project lays the foundation for future commercialization of biogenic nanoparticle production and plasma modification technologies, potentially benefiting both the European biotech industry and global health markets.Work performed and main achievements
Describe the activities performed and the main achievements. Please focus only on technical and scientific part, communication and exploitation activities will be mentioned in another section. For the final report, include the outcomes of the actions.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During this project, significant progress was achieved toward developing an eco-friendly, cost-effective, and clinically relevant nanocarrier platform for brain cancer therapy. The project was structured into three major objectives:
(1) identifying and optimizing a sustainable biosource for mesoporous silica nanoparticle (MSN) synthesis,
(2) developing a plasma-based surface modification system for functionalizing the obtained MSNs, and
(3) evaluating the biological performance of the engineered nanoparticles using an advanced 3D human brain tumor-on-chip model.
Selection and optimization of biosources for MSN synthesis.
Different agricultural and natural silica-rich materials were screened to identify the most suitable precursor for MSN production. Extraction parameters such as acid leaching concentration, calcination temperature, and reaction time were systematically optimized to maximize silica purity and yield. The resulting biosilica samples were characterized by FTIR, XRD, BET, and HR-TEM analyses, confirming well-defined mesoporous structures and high surface areas comparable to conventional chemical routes. This phase established a sustainable protocol to produce high-quality silica nanoparticles entirely from biowaste materials, eliminating the need for energy-intensive and toxic precursors such as alkoxysilanes.
Development of plasma-assisted functionalization.
A dielectric barrier discharge (DBD) plasma reactor was designed, constructed, and optimized for low-temperature surface modification of silica nanoparticles. The plasma system enabled solvent-free, energy-efficient functionalization of MSN surfaces with specific organic moieties, providing enhanced stability and responsiveness for drug delivery applications. Structural and surface analyses verified successful grafting of polymeric layers and functional groups without compromising the mesostructure of the nanoparticles. This work demonstrated, for the first time, the feasibility of using plasma technology to tailor the physicochemical properties of biogenic MSNs for biomedical use.
Evaluation in a human-based 3D microfluidic brain tumor model.
To establish a physiologically relevant in-vitro platform for future evaluation of MSN-mediated drug delivery, a human-based 3D microfluidic glioblastoma model was developed. This model integrates key cellular components of the BBB and the tumor microenvironment, allowing controlled simulation of molecular transport and tumor progression under dynamic flow conditions. The researcher of this project received advanced training in stem-cell culture, endothelial barrier formation, microfluidic chip fabrication, and barrier integrity assays. Using these skills, a co-culture system combining human brain endothelial cells, astrocytes, and glioblastoma cells was successfully established within a microfluidic device, demonstrating stable barrier function and reproducible cell viability under continuous perfusion.
This platform represents a critical preparatory step for the upcoming experimental phase, where the engineered and plasma-functionalized biogenic MSNs will be evaluated for their ability to cross the BBB, release anticancer drugs, and selectively target glioblastoma cells in a dynamic and physiologically relevant environment.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

This project has introduced several innovative methodologies and technological advances that collectively move the field of nanomedicine toward more sustainable, effective, and clinically translatable solutions for brain cancer therapy.
1. Green synthesis of mesoporous silica nanoparticles (MSNs) from biowaste sources.
The project successfully demonstrated a scalable, low-cost, and environmentally friendly approach for producing high-purity silica nanoparticles entirely from natural biowastes such as rice husk and Horsetail plant. This replaces the conventional reliance on expensive and hazardous alkoxysilane precursors, which require high energy and generate large carbon emissions. The developed process combines optimized leaching and calcination conditions, yielding well-structured mesoporous materials with tunable pore sizes and surface areas suitable for drug delivery. This approach represents a major step toward sustainable nanomaterial production, aligning with the principles of the EU Green Deal and Circular Economy.
2. Plasma-assisted functionalization of biosilica nanoparticles.
The development and optimization of a dielectric barrier discharge (DBD) plasma reactor enabled the first demonstration of solvent-free, low-temperature surface modification of biosilica nanoparticles. This technique allows precise control of surface chemistry, introducing functional groups or polymer coatings without using toxic reagents or generating waste solvents. The integration of plasma technology in nanomaterial engineering provides an energy-efficient and clean alternative to conventional chemical grafting or silanization methods, paving the way for broader applications in drug delivery, catalysis, and biomaterials.
3. Establishment of a human-based 3D microfluidic glioblastoma model incorporating the BBB.
A novel microfluidic platform integrating the blood–brain barrier (BBB) and glioblastoma microenvironment has been constructed to provide a physiologically relevant testbed for evaluating nanocarrier transport and therapeutic efficacy. Unlike conventional 2D or static models, this chip-based system mimics key in-vivo parameters such as shear stress, nutrient gradients, and intercellular signaling. It is expected to significantly reduce dependence on animal testing while improving the predictive accuracy of preclinical drug screening. The successful development of this model constitutes a state-of-the-art experimental framework for translational neuro-oncology research.
4. Interdisciplinary integration for future clinical translation.
By combining green chemistry, plasma engineering, and organ-on-chip biotechnology, the project established a unique interdisciplinary foundation for developing next-generation nanocarriers capable of crossing the BBB. The next phase will focus on integrating these technologies to assess the delivery performance of plasma-functionalized MSNs within the established glioblastoma model. This will enable in-depth analysis of nanoparticle–cell interactions, therapeutic efficiency, and biocompatibility in a fully human-relevant platform.
Potential impacts and future needs.
The project’s outcomes contribute to several EU strategic priorities, including sustainable materials development, the replacement of animal testing, and improved therapies for brain diseases. For broader uptake and impact, further scale-up and process validation of the green synthesis method will be required, along with demonstration studies of MSN performance in complex in-vitro and in-vivo systems. In the longer term, IPR protection for the plasma reactor design and the green synthesis method will support commercial exploitation and technology transfer to the pharmaceutical and materials industries. Collaboration with industrial partners and access to innovation ecosystems (e.g. SUCool and Innovent) will also be crucial for moving toward pilot-scale production and market entry. This project advances the state of the art in nanomaterial synthesis, surface engineering, and microphysiological modeling, providing a solid foundation for the next generation of sustainable and effective drug delivery systems targeting brain cancer.

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