Bioorthogonal Reaction For Construction Of Breast Cancer Theranostic Nanoprobes

Background Breast cancer is the most common malignant tumors in women which threatens lives and health.Early detection,diagnosis and treatment are deemed to reverse the progression and reduce the mortality.Purpose To fabricate the acidity-responsive nanoparticles integrated with fluorescence/MR dual-modal imaging and photodynamic therapy based on bioorthogonal reaction,which can be served as breast cancer theranostic nanoprobes.Furthermore,the imaging and photodynamic capacity were evaluated both in vitro and in vivo.Methods Ac₄Man NAz was encapsulated by the amphiphilic block copolymer PEG-b-PLA to form self-assembled micelles（Az-NP）.S-NP was self-assembled from acidic responsive polymer with modification with dibenzocyclooctyne（DBCO）and chlorin e6（Ce6）,further be loaded with oleic acid-coated superparamagnetic iron oxide nanoparticles（OA-Fe₃O₄）.The characterization of Az-NP and S-NP was measured.The tumor cell membrane labeling ability of Az-NP and the cellular toxicity and PDT efficacy of S-NP were well evaluated.We established subcutaneously implanted breast tumor model in nude mouse.The capacity of fluorescence/MR dual-modal imaging and antitumor efficacy of PDT were evaluated in vivo.Serum biochemistry assays were detected to evaluate the biocompatibility.Results The hydrodynamic diameter of Az-NP was 132.1±2.0 nm with superior colloidal stability.The size of S-NP switched to under 10 nm at p H 6.5 owing to the excellent acidity-responsive ability.The metabolic labeling ability of Az-NP could be applied in a broad range of tumor cells.Az-NP/S-NP nanoplatform demonstrated good biocompatibility.The PDT efficacy could be selectively triggered by S-NP driven by tumor acidity to generate abundant ROS in situ via a click reaction with 660 nm irradiation.In vivo MR/fluorescence dual-modal imaging showed that S-NP could specifically target tumor tissues and inhibit tumor growth upon laser irradiation.The tumor inhibition rate of Az-NP/S-NP was 97%,which was significantly higher than the other groups（P<0.001）.TUNEL analysis showed high degree of cell apoptosis.H&E staining showed severe damage of tumor tissue,while normal to normal organs.And no abnormality in serum biochemistry was found.Conclusion The acidity-responsive bioorthogonal strategy could be a promising approach to improve fluorescence/MR dual-modal imaging-guided PDT efficacy of breast cancer.