Review
Pharmacology & Pharmacy
Cristianne J. F. Rijcken, Federica De Lorenzi, Ilaria Biancacci, Rob G. J. M. Hanssen, Marielle Thewissen, Qizhi Hu, Florence Atrafi, Rob M. J. Liskamp, Ron H. J. Mathijssen, Iris H. C. Miedema, C. Willemien Menke van der Houven van Oordt, Guus A. M. S. van Dongen, Danielle J. Vugts, Matt Timmers, Wim E. Hennik, Twan Lammers
Summary: Nanomedicines, specifically the CCPM based on CriPec (R) technology, improve the efficacy and safety of pharmacotherapeutic interventions through targeted drug delivery. These nanomedicines have prolonged circulation time, high concentrations at pathological sites, and low levels of accumulation in healthy tissues. Preclinical and clinical studies have demonstrated their potential for improved anticancer therapy.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Instruments & Instrumentation
Rosario Pignatello, Roberta Corsaro, Angela Bonaccorso, Elide Zingale, Claudia Carbone, Teresa Musumeci
Summary: This study characterized Soluplus(R) nanomicelles to enhance the apparent solubility of drugs in BCS class II. The prepared nanomicelles showed small and stable particle size and could be easily filtered. The freeze-dried powder materials maintained the micelle size upon reconstitution. Additionally, the nanomicelles demonstrated potential applications in topical ocular administration.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2022)
Article
Instruments & Instrumentation
Armin Azadkhah Shalmani, Alec Wang, Zaheer Ahmed, Maryam Sheybanifard, Rahaf Mihyar, Eva Miriam Buhl, Michael Pohl, Wim E. Hennink, Fabian Kiessling, Josbert M. Metselaar, Yang Shi, Twan Lammers, Quim Pena
Summary: Nanomedicine holds promise for enhancing drug combination therapies through co-formulating and co-delivering different drugs. This study developed a size- and release rate-tunable polymeric micelle platform for co-delivery of taxanes and corticosteroids.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Filippo Prencipe, Carlo Diaferia, Filomena Rossi, Luisa Ronga, Diego Tesauro
Summary: Precision medicine relies on innovative management methods for active components, delivering drugs to specific tissues to enhance therapeutic effects and reduce side effects. Utilizing drug-encapsulated micelles for active targeting marks a new frontier in precision medicine. By decorating micelles with targeting bioactive moieties like peptides, it is possible to direct drugs towards a range of molecular targets, particularly on cancer cells and vasculature.
Article
Biochemical Research Methods
Tarun Ojha, Qizhi Hu, Claudio Colombo, Jan Wit, Michiel van Geijn, Mies J. van Steenbergen, Mahsa Bagheri, Hiltrud Koenigs-Werner, Eva Miriam Buhl, Ruchi Bansal, Yang Shi, Wim E. Hennink, Gert Storm, Cristianne J. F. Rijcken, Twan Lammers
Summary: A freeze-drying methodology was developed for drug-containing CCPM, demonstrating that trehalose-protected CPC634 could be rapidly reconstituted with identical critical quality attributes, providing proof-of-concept for future commercialization.
BIOTECHNOLOGY JOURNAL
(2021)
Article
Polymer Science
Mariacristina Gagliardi, Agnese Vincenzi, Laura Baroncelli, Marco Cecchini
Summary: Small hydrophilic drugs are commonly used in systemic administration but have limitations due to poor absorption and fast clearance. Nanoencapsulation of these drugs in compartmented particles, such as liposomes or extracellular vesicles, can enhance their biodistribution, targeted delivery, and pharmaceutical efficacy. In this study, we developed polymeric stabilized reversed micelles as a system for encapsulating hydrophilic drugs. The optimized preparation procedure and stabilization strategy improved the stability of the micelles. These micelles showed potential as drug carriers, with the ability to load and deliver creatine. The results suggest that this system can be further explored for different drug cargoes.
Article
Polymer Science
Russul Mamdooh Al-Nakashli, Cheng Cao, Radhika Raveendran, Hongxu Lu, Martina H. Stenzel
Summary: Polymeric micelles with different drug loading contents were studied to investigate their cellular uptake, penetration, and effects on biological activities. The results showed that micelles with high drug loading content exhibited higher cellular uptake and toxicity.
MACROMOLECULAR CHEMISTRY AND PHYSICS
(2023)
Article
Pharmacology & Pharmacy
Wenqian Yang, Pengwen Chen, Eger Boonstra, Taehun Hong, Horacio Cabral
Summary: Messenger RNA (mRNA) is a promising therapeutic modality, but its fragility and limited intracellular access pose challenges. This study developed pH-responsive cross-linked micelles for stable mRNA delivery and complete release in endosomal pH. The cross-linked micelles increased mRNA delivery efficiency and promoted protein expression.
Article
Biotechnology & Applied Microbiology
Nikita Kaushal, Manish Kumar, Abhishek Tiwari, Varsha Tiwari, Kamini Sharma, Ajay Sharma, Arya Lakshmi Marisetti, Madan Mohan Gupta, Imran Kazmi, Sami Alzarea, Waleed Hassan Almalki, Gaurav Gupta
Summary: This study developed a prednisolone acetate polymeric micelles (PM) system for ocular inflammation related to allergic uveitis. The optimized in situ gel showed superior ex vivo transcorneal permeation with zero-order kinetics, making it a promising candidate for treating anterior uveitis.
Article
Chemistry, Multidisciplinary
Ilaria Biancacci, Federica De Lorenzi, Benjamin Theek, Xiangyang Bai, Jan-Niklas May, Lorena Consolino, Maike Baues, Diana Moeckel, Felix Gremse, Saskia von Stillfried, Asmaa El Shafei, Karina Benderski, Armin Azadkhah Shalmani, Alec Wang, Jeffrey Momoh, Quim Pena, Eva Miriam Buhl, Johannes Buyel, Wim Hennink, Fabian Kiessling, Josbert Metselaar, Yang Shi, Twan Lammers
Summary: Cancer nanomedicines rely on the EPR effect for efficient target site accumulation. This study longitudinally studied the dynamics of the EPR effect during nanotherapy and found that the extent of nanomedicine tumor accumulation is predictive for therapy outcome. It also showed that the interindividual heterogeneity in EPR-based tumor accumulation significantly increases during treatment, especially for more efficient double-dose nanotaxane therapy. These findings highlight the importance of the EPR effect in nanomedicine treatment.
Review
Materials Science, Biomaterials
Meihua Lin, Yu Dai, Fan Xia, Xiaojin Zhang
Summary: Crosslinked polymer micelles, as a drug delivery system, have advantages such as sensitivity to external stimuli, self-healing after damage, and no need for chemical crosslinking. Non-covalent crosslinked micelles can effectively deliver drugs to treatment sites, improve drug bioavailability, and reduce side effects.
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
(2021)
Article
Chemistry, Physical
Jie Bai, Jie Wang, Yecheng Feng, Yongfang Yao, Xubo Zhao
Summary: Polymeric micelles from block copolymers have been studied for cancer drug delivery. The challenge lies in creating stable micelles in biological fluids and unstable micelles at tumor sites. This study proposes a design idea for tunable stability by using zinc coordination-induced core-crosslinked polymeric micelles. The drug-loaded core-crosslinked micelles can disassemble and release cargos in slightly acidic environments, showing adequate toxicity for cancer therapy.
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
(2022)
Article
Pharmacology & Pharmacy
Libing Tian, Rui Pei, Lijuan Zhong, Yuchao Ji, Danhua Zhou, Shufeng Zhou
Summary: This study investigates the targeting efficiency and therapeutic efficacy of aptamer-modified polymeric nano drug carriers encapsulated with DOX in pancreatic cancer treatment. The results indicate that the aptamer-decorated drug delivery system shows enhanced targeting ability and cytotoxic efficacy, suggesting its potential for future targeted delivery of anticancer drugs to treat pancreatic cancer.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Chemistry, Physical
Chufen Yang, Delin Wang, Wenyao Liu, Zexiong Yang, Teng He, Fang Chen, Wenjing Lin
Summary: In this study, folate (FA) modified dual pH/reduction-responsive mixed polymeric micelles were successfully assembled for high loading, controlled release, and active targeted delivery. The micelles showed excellent drug loading capacity and encapsulation efficiency, and demonstrated well-controlled release performance in neutral and acidic environments. Cytotoxicity assays further revealed the superior inhibitory effect of FA-modified micelles on cancer cells. These findings suggest that the developed micelles have great potential for anticancer drug delivery.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Multidisciplinary
Tobias A. A. Bauer, Jonas Schramm, Federico Fenaroli, Svenja Siemer, Christine I. I. Seidl, Christine Rosenauer, Regina Bleul, Roland H. H. Stauber, Kaloian Koynov, Michael Maskos, Matthias Barz
Summary: The efficient manufacturing techniques are necessary for translating innovative nanomaterials into medical products, requiring large-scale high-throughput synthesis with high reproducibility. A continuous flow process is reported for synthesizing pro-drug-loaded core cross-linked polymeric micelles, combining the commonly separated steps into a single process. The microfluidic process allows the production of spherical micelles with low polydispersity values, avoiding toxic solvents and additives. The formed paclitaxel-loaded CCPMs possess pH-responsive release and show improved toxicity profile and therapeutic efficiency.
ADVANCED MATERIALS
(2023)
Review
Chemistry, Multidisciplinary
Romy Ettlinger, Ulrich Laechelt, Ruxandra Gref, Patricia Horcajada, Twan Lammers, Christian Serre, Patrick Couvreur, Russell E. Morris, Stefan Wuttke
Summary: The field of metal-organic frameworks (MOFs), particularly MOF nanoparticles, has seen significant growth in the last two decades. This tutorial review emphasizes the importance of systematic toxicity assessment and discusses the current state of in vitro and in vivo toxicity studies of MOF nanoparticles, as well as the key factors affecting their toxicity.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Materials Science, Biomaterials
Mengjiao Liu, Anshuman Dasgupta, Na Qu, Elena Rama, Fabian Kiessling, Twan Lammers
Summary: The study investigated the impact of loading strategy and drugs' physicochemical properties on drug encapsulation in human serum albumin microbubbles. It was found that preloading and using drugs with high intrinsic HSA binding affinity could improve drug loading in the HSA MB shell. This suggests the potential of exploiting natural bioconjugation interactions for optimal drug delivery using HSA MBs.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2021)
Article
Oncology
Michael Rose, Sebastian Huth, Marc Wiesehoefer, Josef Ehling, Corinna Henkel, Julia Steitz, Twan Lammers, Jennifer Kistermann, Oliver Klaas, Maximilian Koch, Sandra Rushrush, Ruth Knuechel, Edgar Dahl
Summary: The study found that downsized ITIH5 polypeptides can mimic its tumor-suppressive functions and inhibit the growth of various cancer cell lines. Therefore, the VIT domain may play an important role in ITIH5-mediated suppression of tumor cell proliferation, and this research is of great significance for developing anticancer drugs.
Article
Biochemistry & Molecular Biology
Elisa F. Brandt, Maike Baues, Theresa H. Wirtz, Jan-Niklas May, Petra Fischer, Anika Beckers, Bjorn-Carsten Schure, Hacer Sahin, Christian Trautwein, Twan Lammers, Marie-Luise Berres
Summary: This study analyzed the function of chemokine CXCL10 in fibrosis-associated hepatocarcinogenesis and found that CXCL10 has a significant impact on shaping the tumor microenvironment. CXCL10 deficiency attenuated hepatocarcinogenesis and altered tumor-associated immune response and chemokine networks. The results demonstrate that interfering with CXCL10 could be a novel asset for improving therapeutic strategies in HCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Roman A. Barmin, Anshuman Dasgupta, Celine Bastard, Laura De Laporte, Stephan Ruetten, Marek Weiler, Fabian Kiessling, Twan Lammers, Roger M. Pallares
Summary: Gas-filled microbubbles (MB) are used as ultrasound contrast agents and drug delivery vehicles. The properties of MB can be improved by changing the characteristics of surfactants used in their synthesis. It was found that higher-molecular-weight surfactants can increase the shell thickness of MB, leading to higher drug loading capacity and acoustic stability. Additionally, the presence of smaller polymer chains in Triton X-based MB improves drug loading capacity and ultrasound contrast response compared to Tween-based MB.
MOLECULAR PHARMACEUTICS
(2022)
Article
Chemistry, Physical
Rui Zhang, Fabian Kiessling, Twan Lammers, Roger M. Pallares
Summary: Gold nanostars (AuNSs) were synthesized using a simplified one-pot protocol with biocompatible reducing and stabilizing agents. A fractional factorial design of experiments revealed that five factors, including HEPES concentration, Au3+ concentration, temperature, pH, and stirring, controlled the growth, morphology, and optical properties of AuNSs. Additionally, secondary interaction effects between temperature-Au3+ concentration and pH-HEPES concentration were identified, showing larger effects when both factors were changed simultaneously. These findings provide new insights into the synthesis of AuNSs and highlight the importance of characterizing secondary interaction effects for optimizing the properties of gold nanoparticles.
JOURNAL OF PHYSICAL CHEMISTRY C
(2022)
Article
Biochemical Research Methods
Maryam Sheybanifard, Luis P. B. Guerzoni, Abdolrahman Omidinia-Anarkoli, Laura De Laporte, Johannes Buyel, Rut Besseling, Michiel Damen, Ad Gerich, Twan Lammers, Josbert M. M. Metselaar
Summary: Continuous flow manufacturing (CFM) has been proven advantageous in producing drug-loaded nanomedicines, and this study focused on the design and testing of a CFM setup for liposomal nanomedicines. The key parameters that affect the physicochemical characteristics of the liposomes were identified, including total flow rate, lipid concentration, residence time, pressure, and surface area. The integration of in-line measurement allowed for real-time monitoring and adjustment of key parameters during the manufacturing process.
Editorial Material
Biotechnology & Applied Microbiology
Roger M. Pallares, Fabian Kiessling, Twan Lammers
Editorial Material
Nanoscience & Nanotechnology
Alexandros Marios Sofias, Twan Lammers
NATURE NANOTECHNOLOGY
(2023)
Review
Materials Science, Biomaterials
Zhongqian Xi, Rui Zhang, Fabian Kiessling, Twan Lammers, Roger M. Pallares
Summary: This review summarizes and discusses the role of surface curvature in the properties of gold nanostars (AuNSs) and its impact on biomedical and chemical applications, including surface-enhanced Raman spectroscopy, contrast agent performance, and catalysis. The main synthetic approaches to generate AuNSs are examined, as well as their morphology control, benefits, and drawbacks. The optical characteristics of AuNSs are described, and the dependence of these characteristics on nanoparticle morphology is discussed. The unique properties of AuNSs, such as strong electromagnetic fields at the tips and increased hydrophilic environments at the indentations, make them uniquely useful for biosensing, imaging, and local chemical manipulation.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
Review
Pharmacology & Pharmacy
A. Amruta, Dalila Iannotta, Seth W. Cheetham, Twan Lammers, Joy Wolfram
Summary: In recent decades, there has been a significant increase in the development of nanodelivery systems for preclinical and clinical applications, particularly in delivering RNA and protein-based therapeutics. The specific vasculature of organs provides a promising avenue for targeted delivery of nanoparticles and extracellular vesicles to interstitial cells. This article emphasizes the properties of organ-specific vasculature, the strategies for nanodelivery that exploit the organotropism of vasculature, and the challenges and opportunities in targeting and overcoming the endothelial barrier. The impediments in the clinical translation of vasculature organotropism in drug delivery are also discussed.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Article
Multidisciplinary Sciences
Jessica C. C. Hsu, Zhongmin Tang, Olga E. Eremina, Alexandros Marios Sofias, Twan Lammers, Jonathan F. Lovell, Cristina Zavaleta, Weibo Cai, David P. Cormode
Summary: Medical imaging plays a vital role in detecting physiological and pathological processes. The use of contrast agents based on nanomaterials is highly desired for advanced bioimaging techniques due to their unique properties and improved sensitivity. This review discusses the design considerations, physicochemical attributes, and biological behavior of nanomaterial-based contrast agents, as well as common approaches for formulation and characterization. Key applications are highlighted based on different contrast properties. The authors also provide perspectives on current challenges and future advancements in the field.
NATURE REVIEWS METHODS PRIMERS
(2023)
Article
Chemistry, Multidisciplinary
Roman A. Barmin, Mirjavad Moosavifar, Anshuman Dasgupta, Andreas Herrmann, Fabian Kiessling, Roger M. Pallares, Twan Lammers
Summary: Ultrasound (US) is widely used for diagnostic imaging and treatment, and polymeric materials with cavitation nuclei properties can enhance US imaging and promote local drug delivery. This review discusses engineered polymeric materials, such as microbubbles and gas-releasing nanoparticles, that respond to US and their formulation aspects. It focuses on microbubbles and explores the chemical toolbox to enhance their performance in US imaging and drug delivery. The review also summarizes the emerging applications of polymeric microbubbles in molecular imaging, sonopermeation, and gas and drug delivery, highlighting their potential in US imaging and therapy.
Review
Chemistry, Multidisciplinary
Quim Pena, Alec Wang, Orysia Zaremba, Yang Shi, Hans W. Scheeren, Josbert M. Metselaar, Fabian Kiessling, Roger M. Pallares, Stefan Wuttke, Twan Lammers
Summary: Metal complexes are widely used in cancer therapy and nanomedicine has emerged as a powerful tool to enhance their efficacy and reduce toxicity. This critical review discusses the opportunities and challenges of metallodrugs and analyzes the advantages and limitations of their delivery using nanocarriers and metal-nano interactions. The rational combination of coordination chemistry and nanomedicine technology can promote the clinical translation of metallodrugs.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Chemistry, Physical
Rui Zhang, Fabian Kiessling, Twan Lammers, Roger M. Pallares
Summary: This study identified five main factors controlling the growth, morphology, and optical properties of gold nanostars (AuNSs), as well as several secondary interactions. Moreover, the importance of characterizing secondary interaction effects to improve the synthesis of gold nanoparticles with desired properties was highlighted.
JOURNAL OF PHYSICAL CHEMISTRY C
(2022)
