title: CaCO3nanoparticles as an ultra-sensitive tumor-pH-responsive nanoplatform enabling real-time drug release monitoring and cancer combination therapy.
abstract: The exploration of stimuli-responsive nano-theranostics provides powerful tools for simultaneously enhancing the accuracy and efficiency of cancer therapies. Herein, we develop mono-dispersed CaCO3nanoparticles modified with polyethylene glycol (PEG) as a multifunctional nano-carrier for efficient loading of both Mn2+-chelated chlorin e6 (Ce6(Mn)) as a photosensitizer, and doxorubicin (DOX) as a chemotherapy drug. Our CaCO3@Ce6(Mn)-PEG(DOX) nanoparticles, while being stable under physiological pH at 7.4, appear to be highly sensitive to reduced pH and would be rapidly degraded under slightly acidic environment, effectively releasing loaded therapeutic agents. Interestingly, owing to released Ce6(Mn), those nanoparticles show an interesting pH-dependent T1 signal enhancement under magnetic resonance (MR) imaging, which could be utilized for real-time monitoring of drug release. As discovered by MR and fluorescence imaging, intravenously (i.v.) injected CaCO3@Ce6(Mn)/DOX-PEG could gradually accumulate in the tumor, contributing to a superior synergistic anti-tumor effect in the combined photodynamic & chemotherapy. In conclusion, we have developed a tumor-pH-activated nanocarrier based on biodegradable CaCO3nanoparticles, which may be an ideal cancer theranostic nanoplatform with substantial potential for future clinical translation.
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, PR China.
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, PR China. Electronic address: liangzhu.f@gmail.com.
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Feng
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, PR China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, PR China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Radiology, Children's Hospital of Soochow University, Suzhou, 215003, Jiangsu, PR China.
authors.forename: He
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chao
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, PR China. Electronic address: zliu@suda.edu.cn.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D002119:Calcium Carbonate / Q000378:metabolism*; D004317:Doxorubicin / Q000627:therapeutic use; D004337:Drug Carriers / Q000378:metabolism* / Q000627:therapeutic use; D065546:Drug Liberation; D016903:Drug Monitoring; D004357:Drug Synergism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D053758:Nanoparticles / Q000378:metabolism* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002119:Calcium Carbonate
keywords: CaCO(3) nanoparticle; Cancer combination therapy; MR imaging; Real-time monitoring; pH-sensitive