Functional Biomaterials Based On BODIPY Fluorophore For Cancer Therapy

Significant progress had been made of BODIPY fluorescent dyes in tumor diagnosis and therapy area,due to their excellent photophysical properties and easy modification.While at present,most attention have been focused on the synthesis of new BODIPY fluorescent dyes and application in vitro.The shortcomings of BODIPY fluorescent dyes often limit their utilization in vivo,such as the poor solubility of the near-infrared BODIPY fluorescent dyes,the high background of environment interference caused by the lack of environmental responsiveness,increased side effects to the body without targeting ability.Here two kinds of photosensitizers with different substituents and serious of amphiphilic polymers were synthesized based on BODIPY fluorophore in this paper.Then the potential application of these compounds in photodynamics therapy(PDT)and anticancer drugs(nucleic acids)carrier were investigated.Main contents and conclusions about this dissertation are summarized below:1)Two kinds of BODIPY photosensitizers with different substituents,BPOI and BPCI,were successfully synthesized,which were confirmed by 1H NMR,FT-IR.Both materials had low toxicity and could be readily taken up by tumor cells.The ability of synthesized photosensitizers to produce reactive oxygen species were strongly influenced by solvent polarity when the substituent was electron-donating group while no effect was found when the substituent was electron-withdrawing group.Photosensitizer BPOI with electron-donating substituent produced reactive oxygen species with a slow rate in a highly polar environment,while greatly enhanced in lower polarity environment,e.g.in the hydrophobic pocket of the protein,which was expected to be used for environmental-selective photodynamic therapy in tumor cells.2)Serious of amphiphilic polymers were synthesized based on near-infrared BODIPY fluorophore.When regarding the near-infrared BODIPY fluorophore as the unchanged hydrophobic part of the amphiphilic polymers,we synthesized BCPG-1 and BCPG-2 with hydrophilic polyethylene glycol(PEG),BCD-1 and BCD-2 with hydrophilic dendrimer,BCP and BCPSP with hydrophilic polyethyleneimine(PEI).After characterized the ability to form micelles and other physicochemical properties,we investigated the application prospect of these compounds in anticancer drug and nucleic acid carriers.Contributed by the conjugation of redox-activated PEGSS,compounds BCPSP synthesized from BCP showed enhanced stability in aqueous solution and lower toxicity and would be a perfect drugs and nucleic acids carriers.3)Simultaneous tumor imaging,therapy and pharmacokinetic monitoring can offer a safe and effective strategy for cancer therapy.This work describes the design of a fluorescence light-up nanomicelle that can afford precise imaging-guided drug delivery and pharmacokinetic monitoring in a real-time fashion for cancer chemotherapy.The nanomicelle,which contains a boron dipyrromethene-based fluorescent probe as the hydrophobic core and a redox-triggered detachable poly(ethylene glycol)(PEG)shell,can accumulate at the tumor site via enhanced permeation and retention effect.The PEG detachment induced by tumoral and intracellular glutathione(GSH)can destabilize the nanomicelle,leading to fluorescence light up and simultaneous drug release.Importantly,the fluorescence intensities generated by the nanomicelles in different organs are well-correlated with released drug concentrations in both temporal and spatial manners,suggesting its precise role for imaging-guided drug delivery and pharmacokinetic monitoring in vivo.The tumor growth can be effectively inhibited by the docetaxel-loaded nanomicelle formulation,and the nanomicelles are monitored to be excreted via hepatobiliary routes.This nanomicelle for precise imaging-guided chemotherapy provides a safe and robust theranostic strategy for the evaluation of cancer nanomedicine.