Authors:	Sun, Wen
Title:	Photoresponsive Ru-containing block copolymers for anticancer phototherapy
Online publication date:	11-Dec-2017
Year of first publication:	2017
Language:	english
Abstract:	Self-assembled nanostructures of photoresponsive polymers have been used for anticancer phototherapy. The polymer nanostructures as drug-carries display improved bioavailability and extended blood circulation, as compared to small molecule drugs. Light could activate nanostructures and trigger the drug release at the tumor site. Red or NIR light in the “therapeutic window” (650-900 nm) is suited for phototherapy due to its harmless and maximum tissue penetration. However, conventional photoresponsive polymers are sensitive to UV light, which limits their applications in phototherapy due to the harm and poor penetrability of UV light to human tissue. A major goal in this field is to develop photoresponsive polymers that are sensitive to red or NIR light. In this thesis, we reported novel red-light-responsive block copolymers (BCPs) based on photoresponsive Ru complexes. To develop photoresponsive polymers that are sensitive to red light, suited chromophores should be first designed and synthesized. In chapter 2, we synthesized two photoresponsive Ru complexes that can be activated by red light (656 nm). The photoreactions of Ru complexes induced by red light through tissue of different thicknesses were systemically studied. It was demonstrated that red light can activate the complexes after passing through tissue up to 16-mm-thick. Besides, different from conventional chromophores including o-nitrobenzyl, pyrene, and coumarin which are biological inactive, photoactivated Ru complexes are toxic to cancer cells through combined photochemotherapy and photodynamic therapy. Thus, the photoresponsive Ru complexes are promising to construct red-light sensitive polymers for combination phototherapies. In Chapter 3, we made use of red-light-responsive Ru complexes to synthesize three side-chain Ru-containing BCPs with different molecular weights. The BCPs assembled into micelles, vesicles, and large compound micelles. All of the nanostructures can internalize into cancer cells. Red light irradiation released the anticancer Ru complex from the nanostructures and generated singlet oxygen (1O2) in cancer cells. The combined photochemotherapy and photodynamic therapy caused inhibition of cancer cells. In vivo phototherapy based on photoresponsive polymers are still challenging. In Chapter 4, we reported main-chain Ru-containing BCPs and applied this platform for in vivo phototherapy. The BCPs self-assembled into nanoparticles with an average diameter of 180 nm. Photodegradation of the BCPs induced by red light facilitated the release of anticancer Ru complexes and the generation of 1O2, and consequently, the proliferation of cancer cells was efficiently inhibited. In vivo experiments in a mouse model demonstrated that self-assembled nanoparticles can accumulate at tumor sites and inhibited the growth of tumor under red-light irradiation.
DDC:	540 Chemie 540 Chemistry and allied sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 09 Chemie, Pharmazie u. Geowissensch.
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-1383
URN:	urn:nbn:de:hebis:77-diss-1000016887
Version:	Original work
Publication type:	Dissertation
License:	In Copyright
Information on rights of use:	https://rightsstatements.org/vocab/InC/1.0/
Extent:	IV, 151 Seiten
Appears in collections:	JGU-Publikationen