LCN Nanomedicine Symposium 2021

Event Date
Wednesday, 9 June 2021 - 1:00pm
Speaker/Host
Nazila Kamaly
Type
Online

Nanomedicine Symposium 2021

 

MS Teams: Click here to join the meeting

 

Chairs:

Dr. Nazila Kamaly & Dr. Yuval Elani

 

13:00-13:05                         Welcome by Dr. Nazila Kamaly, ICL

13:05-13:10                         Professor Sandrine Heutz, Co-director of the LCN, ICL

13:10-13:40                         Designers Nanomedicines for Brain and Cancer Targeting

Professor Khuloud Al-Jamal, KCL

13:40-14:10                         Phenotypic nanomedicines to the brain

Professor Giuseppe Battaglia, UCL

14:10-14:40                         Biomedical Applications of Magnetic Nanoparticles

Professor Quentin Pankhurst, UCL

14:40-14:50                         Coffee Break

14:50-15:20                         Image Guided Focused Ultrasound triggered Drug Delivery

Dr Maya Thanou, KCL

15:20-15:50                         Developing mRNA therapeutics for chronic disease

Dr Asha Patel, ICL

15:50-16:20                         Fibrinogen-mimicking multi-arm nanovesicles for thrombus-specific delivery of tissue   plasminogen activator and targeted thrombolysis

                                              Dr Rongjung Chen, ICL

16:20-16:30                         Coffee Break

16:30-17:30                         Keynote speakers:  Professor Omid Farokhzad, CEO Seer, Harvard Medical School

Deep and Scalable Proteomics through a Transformative Nanoparticle-Based Approach.

Dr Serafim Batzoglou, Seer

17:30                                    Close

 

 

Abstracts

 

Phenotypic nanomedicines to the brain

Professor Giuseppe Battaglia, UCL

Abstract: Tight control on the selectivity of nanoparticles’ interaction with biological systems is paramount for the development of targeted therapies. However, the large number of tuneable parameters makes it difficult to identify optimal design “sweet spots” without guiding principles. I will present how to  tackle this challenge creating association profiles around the target cell phenotype, I will show how such an approach can be applied using polymersomes functionalised with targeting ligands to identify the most selective combination of parameters in terms of particle size, brush length and density, as well as tether length, affinity, and ligand number. I will show that the combination of multivalent interactions into multiplexed systems enable interaction as a function of the cell phenotype, that is, which receptors are expressed. I will focus on our efforts to enter the brain and deliver within its parenchyma showing how the brain vasculature phenotype changes with the disease.

References:

  • X Tian, D Moreira-Leite, E Scarpa, S Nyberg, G Fullstone, J Forth, D Lourenco-Matias, A Apriceno, A Poma, A Duro-Castano, M Vuyyuru, L Harker-Kirschneck, A Saric, Z Zhang, P Xiang, B Fang, Y Tian, L Luo, L Rizzello, G Battaglia* On the shuttling across the blood-brain barrier via tubules formation: mechanism and cargo avidity bias Science Adv. 2020, 6 (48), eabc4397
  • M.Liu, A.Apriceno, M.Sipin, E.Scarpa, L.Rodriguez-Arco, A.Poma, G.Marchello, G.Battaglia*, and S. Angioletti-Uberti* Combinatorial entropy behaviour leads to range selective binding in ligand receptor interactions Nature Comm. 2020 11, 4836
  • E.S.Kim, D.Kim, S.Nyberg, A.Poma, D.Cecchin, S.Jain, K.A.Kim, Y.J.Shin, E.H.Kim, M. Kim , S. H. Baek ,J . K. Kim, T. Doeppner, A. Ali, J. Redgrave, G. Battaglia*, O. N. Bae*, A. Majid*. LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke Sci. Reports 2020, 10(1), 699.
  • X. Tian, S. Angioletti-Uberti, G Battaglia* On the design of precision nanomedicines. Science Adv. 2020, 6, 4, eaat0919

 

Biomedical Applications of Magnetic Nanoparticles

Professor Quentin Pankhurst, UCL

Abstract: ‘Healthcare Biomagnetics’ – the sensing, moving and heating of magnetic nanoparticles in vitro or in the human body – offers the potential for safe and convenient alternatives for many therapeutic and diagnostic applications. This is leading to the development of products such as remote sensors, mechanical actuators, and therapeutic heat sources. In this lecture a selection of recent examples will be presented and discussed.

 

Image Guided Focused Ultrasound triggered Drug Delivery

Dr Maya Thanou, KCL

Localised drug delivery to tumours may be applied using blood compatible nanosized carriers able to respond to an external stimulus with a triggered drug release. Conventional thermo-sensitive liposomes (TSLs) or similar responsive delivery systems lack the labels for in vivo tracking or clinical imaging and hence the ability to assess the optimal trigger time post systemic administration. We develop dual labelled thermosensitive liposomal (iTSL) delivery system for localised delivery by Focused Ultrasound (FUS) triggered release. In addition to labelling for MRI, we introduced a Near- Infrared fluorescence (NIRF) label which greatly assists real time tracking of the carrier in our murine xenograft cancer model. This in turn allows for optimisation of the FUS conditions and timings, required for triggered-release and functional delivery of the therapeutic drugs to the tumours. We synthesise these as lipid attached conjugates to ensure specific and lasting labelling of the carrier liposomes. MRI contrast enhancement ability and NIRF signals are assessed in vitro and in vivo.  Nanoparticle (iTSLs) kinetics in murine tumours are assessed with optical imaging and at defined time intervals post intravenous injection, FUS was applied to induce a small increase in temperature to 42-43°C for 3-5 min. Imaging reveals both dramatic nanoparticles accumulation and drug release immediately after FUS treatment. Significant tumour growth inhibition is observed for the FUS treated tumours compared to those that were treated only with the drug nanoparticles. The applications of such multifunctional nanotheranostics with short and repeated FUS applications could have a transformative effect on cancer chemotherapy.

 

Fibrinogen-mimicking multi-arm nanovesicles for thrombus-specific delivery of tissue plasminogen activator and targeted thrombolysis

Dr Rongjun Chen, UCL

 Clinical use of tissue plasminogen activator (tPA) in thrombolytic therapy is limited by its short circulation time and haemorrhagic side effects. Inspired by fibrinogen binding to activated platelets, we report a fibrinogen-mimicking, multiarm nanovesicle for thrombus-specific tPA delivery and targeted thrombolysis. This novel system is based on the lipid nanovesicle coated with polyethylene glycol (PEG) terminally conjugated with a cyclic RGD (cRGD) peptide. Our work with human blood demonstrated its highly selective binding to activated platelets and efficient tPA release at a thrombus site under both static and physiological flow conditions. Its clot dissolution time in a microfluidic system was comparable to that of free tPA. These results suggest that the activated-platelet-sensitive multifunctional nanovesicle is a promising platform for effective thrombolytic therapy with minimal undesirable side effects.

 

 

Developing mRNA therapeutics for chronic disease

Dr Asha Patel, ICL

Bio: Dr. Asha Patel is lecturer at the National Heart & Lung Institute, Imperial College London. Her group is investigating RNA therapeutics for chronic disease. Dr Patel carried out her postdoctoral fellowship at Massachusetts Institute of Technology, where she developed degradable vectors for inhaled mRNA delivery to the lung. She gained her PhD in Regenerative Medicine at the University of Nottingham and received a first class honours in Pharmacy from King’s College London.

 Abstract: Messenger RNA can instruct cells to produce specific proteins and holds promise for treating a range of conditions ranging from genetic disorders to infectious disease. However, safe and efficient delivery to non-liver organs remains a challenge. Development of materials that can protect mRNA against degradation and facilitate delivery to the lung will be described. In addition, therapeutic application of mRNA requires precise control over protein production and approaches for transcript engineering to enable predictable pharmacokinetics will also be discussed.

 

 

 

 

 

 

 

 

 

 

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