Polymer nanostructures with aggregation-induced emission properties for bioimaging and drug delivery – AIE-Nanopoly

Polymer nanostructure-based bioimaging systems possess many advantages over traditional ones in terms of sensitivity, signal stability, multiplexing capability and facile surface functionalization for targeting. Polymer nanostructure-based drug delivery systems (DDS) show reduced cytotoxicity and better protection of active molecules and provide drug release control in time and space. Polymersomes (polymer vesicles) are of particular interest as they show high stability and unique encapsulation ability for both hydrophilic and hydrophobic molecules, and their membrane properties can be finely adjusted using a variety of monomers to achieve stimuli-responsive opening. Nevertheless, up to nowadays, few bioimaging nanoparticles and nano-DDS based on polymers reach commercial level. Several challenges remain such as how to image cells/tissues efficiently and track the distribution of drugs, how to enhance the imaging and treatment efficacy, how to achieve controlled release of drugs, etc. Fluorescent polymer nanoparticles studied for bioimaging contain generally conventional organic dyes which suffer from aggregation-caused quenching (ACQ). Recently, luminogens with aggregation-induced emission (AIE) characteristics have emerged as a new class of fluorescent materials for organelles imaging and drug delivery monitoring. The combination of AIE luminogens (AIEgens) with polymer nanostructures, especially polymersomes, will provide innovative approaches to cell/tissue imaging and to in vivo study of drug distribution. However, there are only a few systems reported to date that combine AIE properties with polymer nanostructures self-assembled in well-controlled manners. Studies on AIE polymersomes are just scarce. In this project, we will propose a rational design of AIE polymer nanostructures, especially AIE polymersomes, and develop them as efficient systems for bioimaging and theranostics (combining diagnostics and therapy).
The French teams of this international collaborative project are specialists in the polymer synthesis, the polymer self-assembling and the design of stimuli-responsive polymersomes sensitive to light, temperature and reduction agents, and the Hong Kong team is the frontier research group to design, synthesize and investigate AIE luminescent materials. With the complementary strengths, together we propose to develop: (1) light-up AIE polymersomes and (2) AIE fluorescent polymersomes. (1) The light-up AIE polymersomes represent a totally new system, where water-soluble AIEgen-conjugates are encapsulated in the inner aqueous compartment of polymer vesicles. The stimuli-responsive opening of the polymersomes and the specific cleavage of the AIEgens-conjugates will activate the fluorescence of AIEgens. The polymer nanostructures will ensure the long systemic circulation and favor the in vivo applications. The specific light-up AIEgen-conjugates show advantages of low background interference, high signal to noise ratio, superior photostability and possibly activatable therapeutic effects if pro-drug is introduced in the conjugates. (2) The AIE fluorescent polymersomes take advantage of the big hydrophobic pockets in the polymer membrane that will house AIEgens of a normally rigid hydrophobic nature. We will investigate the photophysical properties of AIE fluorescent polymersomes or polymer nanoparticles on the basis of their molecular and soft-condensed-matter structures in order to obtain ultra-bright fluorescent nanoparticles. When drugs are co-encapsulated with AIEgens, these systems can not only be used for bioimaging, but also for theranostics. Both light-up AIE polymersomes and AIE fluorescent polymersomes will undoubtedly contribute to the development of personal medicine and will also guide the design of new biosensors.