Biodegradable Water-Soluble Cylindrical Block Copolymer Micelles and their Applications in Nanomedicine

Project Information

JTIM

Grant agreement ID: 750527

DOI

10.3030/750527

Project terminated on 31 December 2019

EC signature date 16 March 2017

Start date 15 March 2018

End date 14 March 2020

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 195 454,80

EU contribution

€ 195 454,80

Coordinated by

UNIVERSITY OF BRISTOL
United Kingdom

Periodic Reporting for period 1 - JTIM (Biodegradable Water-Soluble Cylindrical Block Copolymer Micelles and their Applications in Nanomedicine)

Reporting period: 2018-03-15 to 2020-03-14

Summary of the context and overall objectives of the project

Block copolymer (BCP) self-assembly in solution has attracted considerable attention for many decades because it can yield ordered nanoscopic core-shell structures (micelles) with a wide range of morphologies, including spheres, cylinders, lamellae, and vesicles. These aggregates offer potential applications in many fields and cylinders are among the most promising for uses in nanomedicine (e.g. as drug delivery vehicles (DDVs)).

Living CDSA offers the opportunity to create highly uniform populations of precisely designed drug delivery vehicles (DDVs) as it is possible to prepare monodisperse cylinder samples (also called nanofibers) of controlled length and to access block comicelles with tailored segmented structures. A series of monodisperse nanofibers have been fabricated and studied systematically with length optimisation for different targeted applications.

Exciting work including the development of various biodegradable block copolymer systems and the fabrication of novel water-compatible nanofiber assemblies for drug delivery have been accomplished by the MSCA researcher Dr. Jia Tian. Additionally, 2 articles had been submitted to top journals and now one is under review, and 1 article is under preparation. Dr. Jia Tian also presented those work at international conferences and departmental symposia, and highlighted to the general public at University Open Days and a European Researchers’ night. Several other papers have also been drafted from publication and should be submitted in due course.

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

A series of biodegradable block co-polymers were synthesized and characterized. Monodisperse nanofibers of above block co-polymers have been assembled and their morphologies and colloidal stabilities in water have been confirmed by TEM, AMF, cryo-EM, and SAXS which are critical for bio-medical applications.

The monodisperse micelles of have been tested in Xiaoyuan Chen’s group at the NIH in the US, and got promising cellular uptake and loading drug release rate in HeLa cells. Now the properties of the DDV of drug-loaded nanofibers were tested in vivo by tail intravenous injection in tested mouse groups. The cancer therapy test of the DDV of nanofibers showed significant enhanced efficiency compared with those in the control group, which not only show a great cancer theranostic efficacy but also offers an attractive solution for designing powerful theranostic platforms. More results will be updated from Prof. Xiaoyuan Chen’s group in NIH, the MSC fellow Dr. Jia Tian has built long-term relationship with the NIH group which is known for the bio-imaging and nanomedicine design and testing which will benefit his future independent academic career.

All these results have been accomplished and in preparation of publication or submitted in top-ranking journals, and presented at conferences, symposia, and to the general public at University open days, and EU researchers’ events.

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)

Shape, size, and rigidity of nanoparticle therapeutic agents play a key role in determining uptake efficiency, circulation time, and distribution in the body. Studies have shown that cylindrical nanoparticles are among the most promising for applications in nanomedicine but studies of monodisperse structures of controlled length have not yet been possible to date. The formation of uniform biodegradable cylindrical micelles of tunable length for fundamental studies and complex block comicelle analogues as DDVs with targeting and imaging capabilities outlined. Their creation will be made possible by the use of the recently developed living CDSA method. Although cylindrical micelles have been previously examined samples have been polydisperse with no control over length and so detailed information that allows length optimisation for applications is not possible, thus achievements are highly original and innovative and the studies are unprecedented. Furthermore, the ability to prepare segmented micelles allows for functionalization in specific locations. The proposed work on tailored 1D nanoparticles and applications in nanomedicine is at the frontier of the fields of self-assembly, polymer science, and nanomedicine.

Biodegradable Nanofibres