Fluorinated Covalent Organic Polymers For Effective Cancer Photo/Sono-dynamic Therapy

Tumor hypoxia is one of the hostile characteristics of solid tumors owing to the altered metabolic phenotype.Recent progresses show that tumor hypoxia not only promotes tumor growth and metastasis,but also significantly impairs the migration and activation of immune cells of host immune system,thereby leading to the inefficiency of most clinically used cancer treatments.More recently,one promising research direction in the field of nanomedicine is to design the innovative nano-materials to modulate the abnormal tumor microenvironment(e.g.tumor hypoxia)for enhanced cancer treatment without causing additional side effects.In this dissertation,we synthesized a fluorinated covalent organic polymer by sequentially cross-linking meso-5,10,15,20-tetra(4-hydroxylphenyl)porphyrin(THPP)with Perfluorosebacic acid(PFSEA)and polyethylene glycol(PEG),obtaining THPP pf-PEG with excellent photodynamic and sonodynamic therapeutic efficacies.We found that the obtained THPP pf-PEG showed high loading efficiency towards perfluoro-15-crown-5-ether(PFCE)and molecular oxygen,and thereby significantly improved the photodynamic therapeutic effects of THPP.Then,it was shown that the PFCE loaded THPPpf-PEG(PFCE@THPPpf-PEG)upon intravenously injection would adsorb oxygen in the lungs and gradually release oxygen after being accumulated in the tumor sites.As the result,the treatment would enable highly effective tumor oxygenation and thus leading to obviously enhanced photodynamic treatments when tumor were subjected to 660 nm laser irradiation.Moreover,we found that such THPPpf-PEG also showed high loading capacity of an immunomodulator(imiquimod,R837)owing to its porous structure.It was then found that the treatment of intratumoral injection of R837/PFCE@THPPpf-PEG plus localized ultrasonication exposure would not synergistically inhibit the growth of primary tumors,but elicit specific immune memory response to effectively protect the cured mice from tumor rechallenge.This dissertation presents the preparation of innovative fluorinated covalent organic polymers of THPPpf-PEG with efficient loading capacities of PFCE,molecular oxygen and immunomodulatory for effective tumor hypoxia relief and greatly enhanced tumor treatments.