Category Archives: Nanomedicine

Overview:

Nanomedicineis an offshoot of nanotechnology, and refers to highly-specific medical intervention at the molecular scale for curing diseases or repairing damaged tissues. Nanomedicine uses nano-sized tools for the diagnosis, prevention and treatment of disease, and to gain increased understanding of the complex underlying pathophysiology of the disease. It involves three nanotechnology areas of diagnosis, imaging agents, and drug delivery with nanoparticles in the 11,000 nm range, biochips, and polymer therapeutics.

Majority of nanomedicines prescribedcurrently, allow oral drug delivery and its demand is increasing significantly. Although these nanovectors are designed to translocate across the gastrointestinal tract, lung, and bloodbrain barrier, the amount of drug transferred to the organ is lower than 1%; therefore improvements are challenging. Nanomedicines are designed to maximize the benefit/risk ratio, and their toxicity must be evaluated not only by sufficiently long term in vitro and in vivo studies, but also pass multiple clinical studies.

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Market Analysis:

The Global Nanomedicine Market is estimated to witness a CAGR of 17.1% during the forecast period 20172023. The nanomedicine market is analyzed based on two segments therapeutic applications and regions.

The major drivers of the nanomedicine market include its application in various therapeutic areas, increasing R&D studies about nanorobots in this segment, and significant investments in clinical trials by the government as well as private sector. The Oncology segment is the major therapeutic area for nanomedicine application, which comprised more than 35% of the total market share in 2016. A major focus in this segment is expected to drive the growth of the nanomedicine market in the future.

Regional Analysis:

The regions covered in the report are the Americas, Europe, Asia Pacific, and Rest of the World (ROW). The Americas is set to be the leading region for the nanomedicine market growth followed by Europe. The Asia Pacific and ROW are set to be the emerging regions. Japan is set to be the most attractive destination and in Africa, the popularity and the usage of various nano-drugs are expected to increase in the coming years. The major countries covered in this report are the US, Germany, Japan, and Others.

Therapeutic Application Analysis:

Nanomedicines are used as fluorescent markers for diagnostic and screening purposes. Moreover, nanomedicines are introducing new therapeutic opportunities for a large number of agents that cannot be used effectively as conventional oral formulations due to poor bioavailability. The therapeutic areas for nanomedicine application are Oncology, Cardiovascular, Neurology, Anti-inflammatory, Anti-infectives, and various other areas. Globally, the industry players are focusing significantly on R&D to gain approval for various clinical trials for future nano-drugs to be commercially available in the market. The FDA should be relatively prepared for some of the earliest and most basic applications of nanomedicine in areas such as gene therapy and tissue engineering. The more advanced applications of nanomedicine will pose unique challenges in terms of classification and maintenance of scientific expertise.

Key Players:

Merck & Co. Inc., Hoffmann-La Roche Ltd., Gilead Sciences Inc., Novartis AG, Amgen Inc., Pfizer Inc., Eli Lilly and Company, Sanofi, Nanobiotix SA, UCB SA and other predominate & niche players.

Competitive Analysis:

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At present, the nanomedicine market is at a nascent stage but, a lot of new players are entering the market as it holds huge business opportunities. Especially, big players along with the collaboration with other SMBs for clinical trials of nanoparticles and compounds are coming with new commercial targeted drugs in the market and they are expecting a double-digit growth in the upcoming years. Significant investments in R&D in this market are expected to increase and collaborations, merger & acquisition activities are expected to continue.

Benefits:

The report provides complete details about the usage and adoption rate of nanomedicines in various therapeutic verticals and regions. With that, key stakeholders can know about the major trends, drivers, investments, vertical players initiatives, government initiatives towards the nanomedicine adoption in the upcoming years along with the details of commercial drugs available in the market. Moreover, the report provides details about the major challenges that are going to impact on the market growth. Additionally, the report gives the complete details about the key business opportunities to key stakeholders to expand their business and capture the revenue in the specific verticals to analyze before investing or expanding the business in this market.

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Nanomedicine Market Overview 2021: Current Trends And Future Aspect Analysis 2030 The Host - The Host

KAWASAKI, Japan, Oct. 29, 2021 /PRNewswire/ -- Researchers affiliated with Kawasaki INnovation Gateway at SKYFRONT (KING SKYFRONT) and their collaborators report on antibody delivery technology that empowers immunotherapy against glioblastoma and suppresses side effects, and creating smart nanomachines to detect highly invasive cancer after surgery and prevent recurrence.

Tumor-Specific Anti-Cancer Activity

Details

https://tonomachi-ksf.kawasaki-net.ne.jp/ennewsletter/

Research highlight

Antibody Delivery Technology Empowers Immunotherapy against Glioblastoma and Suppresses Side Effects

In this research, Kazunori Kataoka of the Innovation Center of Nanomedicine, Kawasaki, Japan and colleagues developed an antibody delivery technology based on multiple glucosylated polymers conjugated onto antibodies via linkers cleaving in tumor microenvironment.

The delivery technology enhanced the accumulation of anti-PD-L1 antibody (Avelumab) in glioblastoma by 33-fold, compared to unmodified Avelumab by recognizing Glucose Transporter 1.

In orthotopic glioblastoma models, a single administration of the modified Avelumab at 15% of the standard dose achieved 60% complete response rate, with long-term immune memory.

The delivery technology suppressed the immune-related adverse events of Avelumab.

Reference

Yang, T., Mochida, Y., Liu, X. et al. Conjugation of glucosylated polymer chains to checkpoint blockade antibodies augments their efficacy and specificity for glioblastoma. Nat Biomed Eng (2021).

DOI: 10.1038/s41551-021-00803-z

URL: https://doi.org/10.1038/s41551-021-00803-zhttps://tonomachi-ksf.kawasaki-net.ne.jp/pdf/pressrelease02.pdf

Research highlight

Creating Smart Nanomachines to Detect Highly Invasive Cancer After Surgery and Prevent RecurrenceCancer Metastasis and Recurrence Prevention

Matrix metalloproteinases (MMPs) is an enzyme required for cancer cells to metastasize/invade, and cancer cells with higher MMP activity have higher metastasis ability and progress quickly.

Story continues

In this study, Kazunori Kataoka of the Innovation Center of Nanomedicine, Kawasaki, Japan and colleagues created polymersomes (smart nanomachines) that act specifically in tissues that overproduce MMPs, prevent cancer metastasis, and developed a method to remove residual tumor tissue that could not be visually confirmed after surgery.

The scientists simultaneously loaded the cell division inhibitor colchicine and the MMP inhibitor marimastat into MMPs-responsive polymersomes as an enzymatically transformable nanomachine designed to achieve transformation following dePEGylation by cleavage of the inserted substrate peptide by MMPs. The effect on malignant tumors with high MMPs activity was evaluated.

During transformation, nanomachines with exposed guanidine residues easily penetrate into cells, and at the same time, by releasing the contained drugs, it exerts an anti-cancer effect.

Evaluating drug uptake using HT1080 cells derived from human fibrosarcoma that overproduce MMPs, studying pharmacokinetic and nano-bio interaction using a confocal laser scanning biomicroscope and evaluating metastasis inhibitory effect using triple-negative breast cancer transplantation model.

Reference

J. Li, Z. Ge, K. Toh, X. Liu, A. Dirisala, W. Ke, P. Wen, H. Zhou, Z. Wang, S. Xiao, J. F. R. Van Guyse, T. A Tockary, J. Xie, D. G.-Carter, H. Kinoh, S. Uchida, Y. Anraku, and K. Kataoka. Enzymatically Transformable Polymersome-Based Nanotherapeutics to Eliminate Minimal Relapsable Cancer. Advanced Materials, 2021.

DOI: 10.1002/adma.202105254

URL: https://onlinelibrary.wiley.com/doi/10.1002/adma.202105254https://tonomachi-ksf.kawasaki-net.ne.jp/pdf/pressrelease01.pdf

Events

Kawasaki Institute of Industrial Promotion exhibits at BioJapan 2021

The Kawasaki Institute of Industrial Promotion (KIIP) exhibited their booth at BioJapan 2021 between 13-15 October 2021 at PACIFICO Yokohama, Japan. BioJapan is one of Asia's major business partnering events and includes the three exhibitions of biotechnology (BioJapan), iPS technology (Regenerative Medicine JAPAN), and digital technology and life science (health TECH JAPAN).

BioJapan 2021 attracted approximately 900 companies from 25 countries and regions with 14,891 visitorsan increase of 1,104 from 2020.

https://jcd-expo.jp/en/

The Kawasaki Institute of Industrial Promotion (KIIP) established the Tonomachi KING SKYFRONT Cluster Division in April 2020 with the aim of further revitalizing R&D and business activities at KING SKYFRONT and creating a system for continuously creating innovation. By exhibiting at BioJapan, KIIP wants to raise awareness of KING SKYFRONT both within Japan and internationally, with the aim of matching and information gathering with an eye on future cooperation.

Summary of activities at BioJapan 2021

15 interviews with potential industrial partners and businesses

104 visitors to the KIIP booth

Approximately 200 exchanges of business cards

One interview with a local TV station (YouTV)

Further information

KING SKYFRONT https://www.king-skyfront.jp/en/ https://tonomachi-ksf.kawasaki-net.ne.jp/en/

About KING SKYFRONT

The Kawasaki INnovation Gateway (KING) SKYFRONT is the flagship science and technology innovation hub of Kawasaki City. KING SKYFRONT is a 40 hectare area located in the Tonomachi area of the Keihin Industrial Region that spans Tokyo and Kanagawa Prefecture and Tokyo International Airport (also often referred to as Haneda Airport).

KING SKYFRONT was launched in 2011 as a base for scholars, industrialists and government administrators to work together to devise real life solutions to global issues in the life sciences and environment.

Further information

KING-SKYFRONT iNewsletter Publishing TeamTONOMACHI LifeScience Cluster Division, Kawasaki Institute of Industrial Promotion Life Science & Environment research center (LiSE) 1F, 3-25-10, Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa Prefecture, Japan, 210-0821Email: event-ksfcl@kawasaki-net.ne.jp

Kawasaki Institute of Industrial Promotion (KIIP)

Kawasaki Institute of Industrial Promotion was established in 1988 funded 100% from Kawasaki City for the purpose of coping with the hollowing out of industry and changes in the demand structure. In order to realize a higher level of market development, transforming R&D type companies, training technological capabilities to support it, human resources development, understanding market needs, etc., by utilizing the functions of the Kawasaki, KIIP has been contributing to revitalize the local economy by promoting exchanges of local industry information, advancing technology and corporate exchanges with establishment of a R&D institutions, developing creative human resources through workshops and promoting businesses such as expanding sales channels through exhibition business.

https://www.kawasaki-net.ne.jp/

Innovation Center of NanoMedicine (iCONM)

Innovation Center of NanoMedicine (iCONM) started its operation in April 2015 as a core research center in life science field at King SkyFront on the request of Kawasaki city that KIIP utilized national policies as a business operator and proposer. It is a unique research center that the world has ever seen which is designed for the purpose of promoting open innovation through industry-academia-government/medical-engineering collaboration, prepared with state-of-the-art facilities and experimental equipment, that enables comprehensive research and development from organic synthesis / microfabrication to preclinical testing.

iCONM: https://iconm.kawasaki-net.ne.jp/en/index.html

Center of Innovation Program (COI)

The COI program is a research and development program under the Ministry of Education, Culture, Sports, Science and Technology and the Japan Science and Technology Agency. The program employs the backcasting approach and set interdisciplinary and collaborative R&D themes that should be challenged at the present from the issues that are underlying in the future society. Eighteen centers have been established nationwide to realize radical innovation through industry-academia collaboration which cannot be accomplished by industry and academia alone.

The Kawasaki center is the only COI center managed by local governments, not universities, and the research projects carried out there are called COINS (Center of Open Innovation Network for Smart Health).

COI: https://www.jst.go.jp/tt/EN/platform/coi.html COINS: https://coins.kawasaki-net.ne.jp/en/

Cision

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SOURCE KING SKYFRONT

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Latest updates on the research activities at KING SKYFRONT, Japan. - Yahoo Finance

In this series of webinars brought to you by the Cancer Research UK Convergence Science Centre at Imperial College London and The Institute of Cancer Research, London, researchers across the two organisations will discuss key challenges facing cancer research and opportunities for new convergence science approaches to address these. Join us to consider how novel approaches and technologies could shed light on unresolved problems in cancer biology, to innovate new ways to address challenges in cancer and bring pioneering treatments to cancer patients faster.

Hosted by the Convergence Science Centres Scientific Director Professor Axel Behrens, the series aims to support the Centres mission to facilitate collaboration between traditionally separate and distinct disciplines.

Please join us onThursday 4th November, from 15.00-16.00, for two talks from:

Dr Nazila Kamaly Department of Chemistry, Imperial College London

Nanomedicines and their role in modern cancer therapy

Nanoparticle enabled drug delivery and therapy is revolutionising the field of medicine, as we have witnessed recently with the solid lipid nanoparticle based Covid-19 mRNA vaccines. Since the last two decades, the application of nanotechnology in oncology has aimed to provide more effective and safer cancer treatment, with commonly used nanotherapies such as Doxil now on the market as nanosimilars. Considerable technological success has been achieved in this field though we have not seen a new paradigm shift in cancer therapy with nanomedicines. This is in part due to challenges stemming from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and complex chemistries, scale-up, manufacturing and controls required for clinical translation and commercialisation, which the field is actively addressing and will be discussed in this talk.

Dr. Nazila Kamaly is a lecturer in the Department of Chemistry and nanomedicine expert. She uses bioinspired approaches to develop targeted multi-functional polymeric nanomedicines capable of changing their surface or core properties in response to local or up-regulated disease markers for stimuli-responsive and spatiotemporally controlled precise drug delivery. Her lab also develops biomimetic and biomicrofluidic models to better screen and understand nano-bio interactions at the cellular level.

&

Dr Nuria Oliva-Jorge Department of Bioengineering, Imperial College London

Tumour-selective cancer nanotherapies

In this talk, Dr. Oliva-Jorge will describe novel approaches being developed in her group to elicit tumour-selectivity of cancer therapeutics using nanotechnology. It is not uncommon for potent anti-cancer drugs to have dose-limiting toxicity, due to their unintended effects on healthy cells. Using rational nanoparticle design and engineering, we can enable selective nanoparticle uptake and/or drug release in cancer cells only, minimising this way the side effects on healthy cells.

Dr. Nuria Oliva-Jorge is currently an Imperial College Research Fellow in the Department of Bioengineering. An organic chemist by training, Nuria received her PhD in Medical Engineering and Medical Physics from MIT in 2016. Her thesis focused on biomaterials combined with nanotechnology for the local treatment of breast cancer. In 2018, Nuria joined the Almquist Lab at Imperial College London as a postdoctoral fellow to work on nanotechnologies for wound healing and tissue regeneration. Her independent group works at the intersection of biomaterials, biology and medicine to develop novel, smart medical technologies to tackle complex human diseases.

To receive information about how to access this event please emailicr-imperial-convergence.centre@imperial.ac.uk

Please note: This webinar is exclusively available only to colleagues across the Institute of Cancer Research, Imperial College London, the Royal Marsden Hospital and Imperial College Healthcare.

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Converging on cancer seminar series engineering and physical science to advance cancer research (Chemistry and Bioengineering) - Imperial College...

Small (or short) interfering RNA (siRNA) is the predominant RNA interference (RNAi) tool used for instigating short-term silencing of protein-coding genes. Simply put, these are naturally occurring molecules that silence genes that encode specific proteins.

Image Credit: Love Employee/Shutterstock.com

This means that siRNA demonstrates significant potential for therapeutic use, given its capacity to control protein levels. However, one of the main drawbacks with siRNA is that researchers have had difficulty transmitting the molecules to the site of action in the body, the cytosol target of cells, as a result of the bodys immune response.1

To overcome the challenges associated with siRNA delivery, a team of researchers in the Netherlands has been working to develop hybrid nanoparticles that protect and transmit siRNA into target cells.

The system the team is using relies on a combination of liposomes and extracellular vesicles (EVs), which offer unique properties that package and protect siRNA against enzyme degradation.

The hybrid nanoparticles have a hydrophobic coating, thanks to the amphiphilic nature of the liposomes, which provides adequate shielding against the bodys immune response. Additionally, as EVs can easily pass through the outer membrane of a cell, the siRNA can be delivered to the site of action as intended.

The method employed by the researchers uses a dehydration technique to produce a thin lipid film which can then be rehydrated in a water-based mixture containing the EVs and siRNA. This then generates the liposome-EV-siRNA hybrid nanoparticles, which allows for a target-based delivery system.

We show that with increasing relativeEV content in our hybrids, uptake into cells becomes no longer dictated by the liposome content ... Thus, the EV surface molecules now seem to dictate which cells can internalize and process these hybrids.

Pieter Vader, Lead Researcher and Professor of Experimental Cardiology and Regenerative Medicine at the University of Utrecht

By modifying the hybrid formulation and experimenting with the liposome to EV ratio, the researchers found that it was possible to choose into which cells the siRNA would take. The team also discovered that various cell types had the capacity to receive the hybrid nanoparticles without a toxic or adverse reaction this included kidney, nerve and ovarian cell types.

The ability to alter the ratio of the liposome-EV-siRNA formulation is important in designing cell-targeting drugs as it potentially means that only diseased cell types would be targeted, reducing any risk or undesirable side-effects.

Thus, hybrid nanoparticles could integrate the functional properties of both liposomes and EVs and offer a best of both worlds particle for the therapeutic delivery of siRNA.1

The team also looked at the therapeutic outcome when the hybrid formulation was induced with EVs from a specific stem cell population: the results remarkably demonstrated recovery and healing in breast cancer cells. This shows great promise for the future of drug development, especially when designing new drugs that target cancer and degenerative diseases.

While the results of this study make significant strides for the use of hybrid nanoparticles in siRNA delivery, Vader and his team have some way to go before this treatment technology will be rolled out commercially.

Its too soon to tell where the most potential lies for our delivery system, but we know that EVs derived from progenitor cells have intrinsic regenerative properties ... Thus, regenerative medicine applications seem most logical.

Pieter Vader, Lead Researcher and Professor of Experimental Cardiology and Regenerative Medicine at the University of Utrecht

Despite being some way off commercial viability, this recent study clearly demonstrates future potential for using hybrid nanotechnology for effective drug delivery to treat various cancers and other difficult-to-treat, degenerative diseases.

Continue reading: Manifesting Multidisciplinary Nanomedicine Research with the Multiscale Metrology Suite

Evers, M., Et. Al. (2021) Functional siRNA Delivery by Extracellular VesicleLiposome Hybrid Nanoparticles.Advanced Healthcare Materials, Available at: https://doi.org/10.1002/adhm.202101202

Disclaimer: The views expressed here are those of the author expressed in their private capacity and do not necessarily represent the views of AZoM.com Limited T/A AZoNetwork the owner and operator of this website. This disclaimer forms part of the Terms and conditions of use of this website.

Originally posted here:
Using Hybrid Nanoparticles to Deliver siRNA to Different Cell Types - AZoNano

AZoNano speaks to Dr. Zahra Rattray about the impact of the new Multiscale Metrology Suite (MMS) on thedevelopment of the field of nanomedicine. Continue readingfor an insight into how this new, multidisciplinaryfacility is at the forefront of utilizing nanotechnology for pharmaceutical research.

My name is Zahra Rattray, and I am a Chancellors Research Fellow in Translational Pharmaceutics at the University of Strathclyde Institute of Pharmacy and Biomedical Sciences. What inspired me to pursue a career in nanotechnology for health was working within the drug discovery sector and seeing how many promising candidate compounds would fail at later development stages due to formulation challenges or their safety profile.

Using nanotechnology, we could salvage the therapeutic potential of these compounds and ultimately develop life-saving drugs. Since then, I have become very interested in researching the biological performance of nanotechnology drugs or developing new strategies such as targeting ligands to enable drug delivery.

My involvement started during graduate school, where I studied endogenous ligands such as transferrin with a view to harnessing their potential for drug delivery. Following this, I have been involved in pharmaceutical industry pipeline projects developing nanomedicine products; my research team studies the development of bioanalytical pipelines to analyze nanotechnologies.

The widespread use of mRNA lipid nanoparticle vaccines during the COVID-19 pandemic has demonstrated the need for the rapid deployment of nanotechnology for areas of unmet clinical need. The nanotechnology sector has an opportunity to use such momentum and lessons learned from the pandemic and apply this to other therapeutic areas such as oncology.

Image Credit:Viacheslav Lopatin/Shutterstock.com

The Multiscale Metrology Suite will enable the comprehensive physicochemical analysis of novel nanomaterials and their interactions with biomacromolecules contained within biological fluids such as blood. Areas benefiting from this work the most will be novel nanomaterials requiring a comprehensive understanding of product parameters or the impact of the manufacturing process on product characteristics.

Using a data-driven approach, their clinical and commercial translation timelines can be accelerated through deeper product understanding.

In addressing the translational obstacles to nanotechnology implementation in health, we can look to other disciplines for technological solutions or bringing a new perspective to solving existing challenges. The insights and perspectives a multidisciplinary approach delivers can provide transformative and disruptive solutions to some of the grand challenges we face.

A good example is how field flow fractionation (FFF) entered the arena in the 1960s with a limited range of researcher groups investing in this technology. It is only in the past few years that FFF implementation in the bio- and nanotechnology sectors entered a rapid growth phase.

The Multiscale Metrology Suite (MMS) facility will collaborate with academics, industry, and government bodies to ensure its strategic relevance to drug discovery. The MMS will remain world-leading and competitive through incorporating new technological advancements in the analytical and nanotechnology sectors.

Image Credit: FGC/Shutterstock.com

Some of the major obstacles nanotechnology faces is the clinical translation of these products. These obstacles can range from the unknown biological performance of new chemistries to the reproducible manufacture of nanomedicines with consistent key critical quality attributes. The more understanding we can develop about a product and process from the early development stage, the more likely the risk of late-stage pipeline attrition can be mitigated.

I believe that by using a team-based, interdisciplinary approach, we can tackle the grand challenges facing nanomedicine translation. By working across traditional discipline boundaries, we can better understand the biology being targeted, which product attributes are suitable for the biological target, and how we can control these through process design.

Image Credit:Anucha Cheechang/Shutterstock.com

The Multiscale Metrology Suite (MMS) is a unique, bespoke setup that will combine electric, centrifugal and asymmetric field-flow fractionation modes with a range of physical and chemical detectors.

Using this suite, we will be able to measure solution-phase properties of nanomaterial prototypes dispersed in their formulation vehicle or probe their interactions with biomacromolecules in blood components. This will provide information on formulation attributes and the early assessment of interactions with biological fluids. Some examples of parameters we are particularly interested in multiplexing the high-resolution analyses of size, charge, and shape factor (rg/rh) with changes occurring in the chemistry of nanoparticles using Raman analysis or inductively-coupled plasma mass spectrometry.

The MMS will also explore multiplexation with other detectors such as mass spectrometry for proteomics analysis of the nanoparticle corona proteome and high-resolution analysis of particle concentrations using nanoparticle tracking analysis (NTA).

In the era of precision medicine, the ability to fuse large clinical datasets with advanced bioanalytical tools will be transformative in nanomedicine design and selection for patients. Developing a deeper understanding of how nanomedicines interact with biological moieties enabled through advances in analytical technologies will provide the opportunity for us to reverse-engineer new prototypes for optimal safety and efficacy in areas of unmet clinical need.

We will work with our partners and collaborators to harmonize protocols and methods for the analysis of nanomedicine prototypes in an attempt to achieve consistency in the measurement and reporting of nanomedicine attributes.

https://gtr.ukri.org/projects?ref=EP%2FV028960%2F1

Dr. Zahra Rattray is a Chancellors Research Fellow in Translational Pharmaceutics at the Strathclyde Institute of Pharmacy and Biomedical Sciences in Glasgow.

Dr. Rattray is an interdisciplinary translational pharmaceutical scientist with over 10 years experience of working in the academic, industry, and clinic sectors developing a diverse molecule portfolio. Zahra received her PhD in Drug Delivery from the University of Manchester in 2013, and completed a postdoctoral research position at Manchester, developing new analytical pipelines for profiling antibody drug product stability.

Zahra has significant formulation experience from her time at AstraZeneca Pharmaceuticals as both a pre-clinical and late-stage formulation scientist. Zahra completed a postdoctoral research position at the Yale School of Medicine in partnership with Patrys Ltd where she explored cell-penetrating autoantibodies as DNA damage repair agents for the treatment of glioblastoma, and as targeting ligands for drug and gene delivery systems.

Since fall 2018, Dr Rattray has been a Chancellors Research Fellow at the University of Strathclyde. Her team explores the development of bioanalytical measurements for profiling the nanoparticle protein corona and the role of nuclear import in cancer progression.

Disclaimer: The views expressed here are those of the interviewee and do not necessarily represent the views of AZoM.com Limited (T/A) AZoNetwork, the owner and operator of this website. This disclaimer forms part of the Terms and Conditions of use of this website.

Link:
Manifesting Multidisciplinary Nanomedicine Research with the MMS - AZoNano

image:Left: Primary tumor or overt metastasisCenter: Center: Pre-metastatic nicheRight: Post-surgical wound view more

Credit: 2021 Innovation Center of NanoMedicine

Summary:Matrix metalloproteinases (MMPs) is an enzyme required for cancer cells to metastasize/invade, and cancer cells with higher MMP activity have higher metastasis ability and progress quickly.In this study, we created polymersomes (smart nanomachines) that act specifically in tissues that overproduce MMPs, prevent cancer metastasis, and developed a method to remove residual tumor tissue that could not be visually confirmed after surgery.We simultaneously loaded the cell division inhibitor colchicine and the MMP inhibitor marimastat into MMPs-responsive polymersomes as an enzymatically transformable nanomachine designed to achieve transformation following dePEGylation by cleavage of the inserted substrate peptide by MMPs. The effect on malignant tumors with high MMPs activity was evaluated.During transformation, nanomachines with exposed guanidine residues easily penetrate into cells, and at the same time, by releasing the contained drugs, it exerts an anti-cancer effect.Evaluating drug uptake using HT1080 cells derived from human fibrosarcoma that overproduce MMPs, studying pharmacokinetic and nano-bio interaction using a confocal laser scanning biomicroscope and evaluating metastasis inhibitory effect using triple-negative breast cancer transplantation model, the results were published in Advanced Materials (IF = 30.849 in 2021).

J. Li, Z. Ge, K. Toh, X. Liu, A. Dirisala, W. Ke, P. Wen, H. Zhou, Z. Wang, S. Xiao, J. F. R. Van Guyse, T. A Tockary, J. Xie, D. G.-Carter, H. Kinoh, S. Uchida, Y. Anraku, and K. Kataoka, Advanced Materials, 2021.DOI: 10.1002/adma.202105254URL: https://onlinelibrary.wiley.com/doi/10.1002/adma.202105254

October 8, 2021, Kawasaki (Japan) and Hefei (China): The Innovation Center of NanoMedicine, Kawasaki Institute of Industrial Promotion (Director General: Kazunori KATAOKA, location: Kawasaki-ku, Kawasaki-City; abbreviated name: iCONM), in collaboration with the Chinese Academy of Science (CAS) Key Laboratory of Soft Matter Chemistry (USTC: University of Science and Technology), has created nanomachines that detect MMPs (matrix metalloproteinases), a principal enzyme for cancer cells to invade normal tissue, and deliver anticancer drugs according to an announcement in the journal Advanced Materials (IF = 30.849). As it can target highly invasive cancer cells, it is expected to inhibit cancer metastasis and recurrence.

Cancer is known as a malignant tumor due to its characteristics of metastasis, recurrence, and invasion, and preventing them is one of the most effective ways for treatment. When cancer cells metastasize, they need to pass through (invade) normal tissues, and in doing so, they use extracellular proteases (proteolytic enzymes) called MMPs to destroy the fibrous tissue (matrix) that binds cells to cells and tissues to tissues. In this study, we focused on tissues and cells that overproduce MMPs and incorporated the cell division inhibitor colchicine and the MMP inhibitor marimastat into MMPs-responsive polymersomes as an enzymatically transformable nanomachine (ETN). The ETN was designed to possess an amino acid sequence that serves as a specific cleavage site for MMPs and thus be capable of releasing the PEG and exposing the guanidine residue after cleavage. In the drug uptake experiment using human fibrosarcoma-derived HT1080 cells, we found that the fluorescently labeled ETN (Cy5-ETN) had a 10-fold higher uptake than that of an inert vehicle without enzymatic transformation behavior. High cellular uptake enabled strong cytotoxicity of colchicine-loaded ETN with IC50 = 0.015 M compared to the inert vehicle with IC50 = 0.402 M.Observation of mice treated with ETN using confocal laser scanning biomicroscopy showed no leakage out of blood vessels in the auricle and normal liver; strikingly, the nanomachines were found to extensively invade the tumor-associated tissues in breast cancer with high MMPs expression.

In pharmacological experiments with mice, we evaluated the antitumor effect for primary and secondary tumor using MDA-MB-231/LM2 (human) and 4T1 (mice) triple-negative breast cancer models. As a result, the ETN simultaneously encapsulating with colchicine and marimastat had a strong antitumor effect and prolonged survival in both triple-negative breast cancer models. In addition, on the basis of metastasis-prone phenotype of this model after orthotopic transplantation, the ETN was also confirmed to efficiently inhibit lung metastasis because of residual tumor targetability. Our results prove an applicable technology for not only to cancers but also to other diseases with high expression of MMPs.

Kawasaki Institute of Industrial Promotion (KIIP)Kawasaki Institute of Industrial Promotion was established in 1988 funded 100% from Kawasaki City for the purpose of coping with the hollowing out of industry and changes in the demand structure. In order to realize a higher level of market development, transforming R&D type companies, training technological capabilities to support it, human resources development, understanding market needs, etc., by utilizing the functions of the Kawasaki, KIIP has been contributing to revitalize the local economy by promoting exchanges of local industry information, advancing technology and corporate exchanges with establishment of a R&D institutions, developing creative human resources through workshops and promoting businesses such as expanding sales channels through exhibition business.https://www.kawasaki-net.ne.jp/

Innovation Center of NanoMedicine (iCONM)Innovation Center of NanoMedicine (iCONM) started its operation in April 2015 as a core research center in life science field at King SkyFront on the request of Kawasaki city that KIIP utilized national policies as a business operator and proposer. It is a unique research center that the world has ever seen which is designed for the purpose of promoting open innovation through industry-academia-government/medical-engineering collaboration, prepared with state-of-the-art facilities and experimental equipment, that enables comprehensive research and development from organic synthesis / microfabrication to preclinical testing.iCONM: https://iconm.kawasaki-net.ne.jp/en/index.html

University of Science and Technology of China (USTC)The University of Science and Technology of China (USTC) is a public research university of China with scientific and technological research as core strength, under the leadership of the Chinese Academy of Sciences (CAS). Its foundation in 1958 was hailed as "A Major Event in the History of Chinese Education and Science.". USTC has three National Research Institutions and 6 State Key Laboratories and 18 Key Laboratories of the CAS. USTC actively promotes cooperation and exchange with around 100 universities and research institutions in more than 30 nations and regions. In recent years, USTC is ranked in the world's top 100 universities in the most-widely read university rankings.USTC: http://en.ustc.edu.cn

October 8, 2021

Advanced Materials

Enzymatically Transformable Polymersome-Based Nanotherapeutics to Eliminate Minimal Relapsable Cancer

7-Oct-2021

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Creating smart nanomachines to detect highly invasive cancer after surgery and prevent recurrence - EurekAlert