Synthesis Of Highly Water-soluble Theranostic Nanomaterials For Nir-? Optical Imaging & Tumor Therapy

Fluorescence imaging in the NIR-? window,a novel optical imaging technology,demonstrates superiorities of high spatial and deep tissue penetration and negligible autofluorescence,which are beneficial for accurate diagnosis of tumor.To achieve the biological application of NIR-?fluorophores,experts often use amphipathic polymer and hydrophobic fluorophores self-assemblely to form nanoparticles.However,the formed nanoparticles have unstable transportation when applied in vivo,which reduces the imaging quality.In addition,the synergy of chemotherapy and phototherapy guided by optical imaging technology has also attracted much attention,but due to poor diagnostic accuracy,poor physiological stability,low drug loading,and uncontrollable drug release,the effectiveness of synergistic treatment has been hindered.In view of the above two problems,this paper has developed two types of water-soluble NIR-? fluorescent probes for NIR-?imaging guided photothermal treatment and chemotherapy.The specific contents of this paper are as follows:(1)Preparation of PEG-modified NIR-? fluorescent probe and its biological imaging application Firstly,we select 2-(9,9-bis(6-bromohexyl)-9-fluorene-2-borate and 4,9-bis(5-bromothiophen-2-yl)-6 with strong electron acceptors,7-bis(4-(hexyloxy)phenyl)-[1,2,5]thiadiazolo[3,4-G]quinoxaline(TTQ)as a electron acceptor,and then we prepared a small organic molecule(TTQ-FBr4)through suzuki reaction.Finally,the PEG chain modified water-soluble NIR-? fluorescent probe(TTQ-F-PEG)was prepared by the Click reaction synthesis.The TTQ-F-PEG has good performance in water and its hydrodynamic radius is 72 nm.The TTQ-F-PEG probe has strong absorption in the near-infrared region of 700-900 nm,and can produce strong NIR-? fluorescence signal at 1052 nm under 808 nm laser excitation.And it has good photostability and physiological stability.TTQ-F-PEG can achieve high-resolution NIR-?fluorescence imaging of blood vessels and tumors(2)Preparation of multifunctional glycopolymers for NIR-? fluorescence imaging-guided stimuli-responsive Chemo-Photothermal combination therapy Here,we developed a NIR-? dye-based multifunctional glycopolymer(TTQ-TC-PFru)as drug-carrier and constructed stimuli-responsive PFru-BTZ-PBOB nanoparticles to achieve NIR-?fluorescence imaging-guided chemo-photothermal combination therapy of cancers.This multifunctional glycopolymer not only serves as the contrast agent for FI but also as the photothermal agent for photothermal therapy(PTT).Meanwhile,the fructose polymer on TTQ-TC-PFru forms a stable boronic acid-catechol conjugate with the dipeptidyl boronic acid proteasome inhibitor bortezomib(BTZ)to achieve high drug loading with satisfactory physiological stability and controlled drug release in the acidic tumor microenvironment.In addition,one BOB-containing copolymer POEGMA-co-PBOB was introduced to further improve the stability of the system.In living tumor-bearing mice,the PFru-BTZ-PBOB successfully induced significant tumor regression through NIR-? FI-guided chemo-photothermal combination therapy.