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Targeted delivery for liver cancer treatment

Final Report Summary - HEPTAG EXCHANGE (Targeted delivery for liver cancer treatment)

1. Summary of project objectives
HEPTAG EXCHANGE is an exchange-based programme to enable the development of biomarker functionalised vehicles. The programme involves technology transfer of advanced methods from the synthesis of pharmaceutical materials, to targeted drug delivery for cancer cell imaging and treatment. The joint programme has three functional types of objectives, namely, strategic objectives, knowledge transfer objectives, and research objectives. It strategically lays the foundation for long term collaboration in building the EU network of excellence (NoE) on liver cancer treatment and integrating the liver cancer market from the ageing population in common. The incentive for knowledge transfer aims to nurture a new generation of researchers through a variety of academic and training activities. These activities enable joint research efforts yielding innovative ideas and new opportunities of developing targeted cancer therapies. To achieve these objectives, five work packages (illustrated in Figure 1, attached) were set up and activated, with specific tasks and tangible deliverables for the exchanged researchers in completely new research infrastructures and cultures. The research and generated interaction through this exchange programme is expected to provide huge benefits to communities and societies, to develop the scientific skill base and give momentum to researchers’ personal success and academic satisfaction.

2. The work performed from 01/01/2012 to 31/12/2015
2.1 Programme Website
The HEPTAG EXCHANGE website ( features: news highlights, programme summary, participants, work packages, exchange plan, courses, publications and homepage with programme logo and contact details. News highlights are regularly updated, with fourteen editions published over the duration of the project, January 2012 – December 2015. The website is open to the public and will be maintained for the foreseeable future.

2.2 Researcher Exchanges from 2012 to 2015
The HEPTAG EXCHANGE project successfully fulfilled almost 47 of the planned 51 person-month staff exchanges over four years from 2012-2015, supporting researcher exchanges at two different levels, the ESR (Early Stage Researcher) and ER (Experience Researcher). In 2012, eight ESR months were allocated to the University of Navarra, Spain, for Work Package 2 (Formulation). This comprised of two ESRs from Navarra exchanging to Sichuan University, China, for four ESR-months each. In 2013, for Work Package 1 (Pharmaceutical materials) two ER months were allocated to Sichuan, exchanging to the University of Wolverhampton (UoW), UK, for Work Package 4 (Cancer cell treatment), including attending the First Project Meeting at Navarra in 2013. From 2014 to 2015 more than 33 ESR months were fulfilled with researcher exchanges between Navarra and Sichuan and between UoW and Sichuan. Additionally, 4 ER months were spent at Navarra and Sichuan. Finally, UoW hosted an ER exchange from Florida International University (FIU), USA, but was unable to send a researcher back to FIU due to financial constraints.

2.3 Project Meetings from 2012 to 2015
HEPTAG EXCHANGE originally planned two Workshops, one in month 44 and the other in month 46, serving as important events for partner exchange. During the project report period, it was possible to organise three Workshops:
i) The first project meeting, in conjunction with the 19th International Symposium on Microencapsulation, was held at Navarra in September 2013. Participants from Sichuan, UoW and Navarra presented their collaborative work during the meeting. The board had a programme committee meeting and exchanged mutual interests for further collaboration.
ii) The second project meeting was held at Sichuan in October 2015. Representatives from Sichuan, Navarra and UoW attended and presented at the meeting.
iii) The final project meeting was held at UoW in December 2015. Dr. Sharan Ramaswamy from FIU presented his work and the board of management committee exchanged interest in further collaboration.

2.4 Programme management from 2012 to 2015
HEPTAG EXCHANGE arranged and managed partner activities, routine activities, and prepared progress reports to the European Commission. The four partner activities were: staff exchange comprising of ESRs and ERs exchange; the training programme, accommodating modular block training and in-proposal training; workshops, designed as project meetings to facilitate knowledge and expertise exchange; and joint publications, promoting expertise integration for healthcare issues. The priority activity, staff exchange, was arranged collectively through host and home institutions and facilitated by the coordinating institution. Issues related to staff exchange include ESRs and ERs selection, financing, visa application, overseas insurance, off-site and on-site monitoring, and after exchange collaboration. The programme management also carried out a list of routine activities which are categorised as: financing the researcher exchange; designing, preparing and updating the programme website; on-site monitoring progress of researcher exchanges; harmonising courses and skills training for ESRs; and facilitating publications in different media for various audiences and readers. To enable the financial support for the exchange of Chinese Researchers, the WP5 team, together with the REA Project Officer, moderated the relevant items in the grant agreement in 2014. As required by FP7-People-IRSES grant agreement, the coordinator, supported by the management team, prepared progress reports: periodic reports; mid-term report; and the final report in 2014, 2015 and 2016.

3. Main results achieved so far
3.1 Online public profiling
HEPTAG EXCHANGE created an online public profile via the programme website, hosted by the UoW, which is kept current with regular updates to the news highlights, exchange plan, and publications sections. It is dynamic by design, in order to maximise impact and public influence. During the HEPTAG EXCHANGE project report period, additional dynamic features were added into Courses, enabled as training programme, for further exploitation.

3.2 New research and teaching –enabled training collaboration
HEPTAG EXCHANGE (PIRSES-GA-2011-295218) creates a sustainable core-shell structure model for attracting new collaboration. HEPTAG EXCHANGE project provided as the core-project to form the shell-network. Under this core-shell structure model, a Nigerian supported PhD student joined the shell-network and exchanged to Navarra, Spain in 2013. An ER selected from the shell-network, was trained in the in-proposal writing, winning the prestigious FP7-MC-IIF-2013 (€299,850) in 2013 and becoming one of core projects in our core-shell structure model. Another ER selected from the shell-network was actively engaged in proposal writing in 2015. An ESR also selected from our HEPTAG EXCHANGE core project, worked jointly with host and home supervisors and submitted a small grant proposal in 2015. HEPTAG EXCHANGE sustainable core-shell structure model was presented and delivered to continental Europe and China, successfully attracting ERs from Denmark; ZJUT and China into new research and teaching –enabled training collaboration (2015).

3.3 Identification and integration of research findings for cancer cell imaging and treatment
HEPTAG EXCHANGE undertook planned scientific activities which are summarised as pharmaceutical materials enabled dosage form for cancer cell treatment. The research findings on pharmaceutical materials include PEG based block polymers (2012) and ligand conjugated block polymers (2015). Dosage forms for parenteral and oral administration were developed for targeted cancer therapeutics. Both dosage forms exploit the potential of nanoparticles with or without ligand conjugation. Particle sizes, surface charges, drug loading capacity, controlled drug release and IC50 of the drug in specific dosage form were investigated during the project report period. Research findings were published in conferences and journals from 2012 to 2015, with further publications planned for 2016. Ligands for active targeting include folate, pellulan and lactose, together with passive targeting through particle size control and with pH triggered release for cancer treatment. The design of vehicle materials also introduced peptide moieties for dual delivery of genes and anticancer drugs.

3.4 New training programme from HEPTAG EXCHANGE researcher exchange
HEPTAG EXCHANGE set up a training programme (Figure 3, attached) during the project report period. The modular block training was introduced in 2012 to meet the requirement of ESRs who were exposed to new research and cultural environments. The training blocks were targeted at immediate needs such as skills shortage of pharmaceutical scientists in an organic chemistry area and organic chemists in a biomedical science lab. All exchange researchers dealt with achievable targets in a very limited time frame.

3.5 Sharing intellectual properties before, during and after the exchange period, growing research strength.
HEPTAG EXCHANGE highlights the importance of the integration of human and natural resources in the training programme. Experience and feedback of ESRs, host and home institutions was collated in 2012 and the resulting training was integrated into a collaborative approach to each exchange. A longer term view of the project work was encouraged, an exemplar case being the ESR from UoW to Sichuan who commenced her whole PhD project in China, transferring that knowledge back to UoW on her return. This ESR was selected for in-proposal training, optimising her CPD achievement.

4 Final results and their potential impact and use
During the HEPTAG EXCHANGE project report period, an additional training programme was created for a sustainable core-project/shell-network structure model. This model is CPD driven enabling the HEPTAG EXCHANGE project to have great impact in knowledge transfer and expertise integration. Most ESRs were trained in the modular block training scheme and an exceptional ESR was trained through exploitation of the whole training set-up. The training programme maximised the potential of ESRs and ERs for further and long term collaboration. Through HEPTAG EXCHANGE project practice, the coordinating institution is aware of the skills gap between EU and China and building long term research collaboration requires the critical mass of researchers being trained in the training programme. This is the drive of the concept of the sustainable core-shell structure model, which has proven to be feasible in this HEPTAG EXCHANGE project. With successful core projects, the shell network grows faster. This enables more in-proposal training and more winning bids. Through HEPTAG EXCHANGE shell-network, the UK conglomerate of APSGB/MRC Technology/EMIG/UKTI/CBBC successfully held a meeting in London in 2014 for UK/China Collaboration in pharmaceutical industry research and development. The exploitation of the HEPTAG EXCHANGE training programme kindled mutual interest in teaching-enabled training on the topic of pharmaceutical sciences between UK and China.