title: Charge convertibility and near infrared photon co-enhanced cisplatin chemotherapy based on upconversion nanoplatform.
abstract: Optimal nano-sized drug carrier requires long blood circulation, selective extravasation, and efficient cell uptake. Here we develop a charge-convertible nanoplatform based on Pt(IV) prodrug loaded NaYF4:Yb,Tm upconversion nanoparticles (UCNs), followed by coating a layer of PEG-PAH-DMMA polymer (UCNs-Pt(IV)@PEG-PAH-DMMA). The polymer endows the platform with high biocompatibility, initial nano-size for prolonged blood circulation and selective extravasation. Especially, the anionic polymer can response to the mild acidic stimulus (pH ∼6.5) of tumor extracellular microenvironment and experience charge-shifting to a cationic polymer, resulting in electrostatic repulsion and releases of positive UCNs-Pt(IV). The positive UCNs-Pt(IV) nanoparticles have high affinity to negative cell membrane, leading to efficacious cell internalization. Simultaneously, the ultraviolet (UV) light emitted from UCNs upon near-infrared (NIR) light irradiation, together with the reductive glutathione (GSH) in cancer cells efficiently activate the Pt(IV) prodrug to highly cytotoxic Pt(II), realizing NIR photon improved chemotherapy. The experimental results reveal the charge convertibility, low adverse effect and markedly enhanced tumor ablation efficacy upon NIR laser irradiation of this smart nanoplatform. Moreover, combining the inherent upconversion luminescence (UCL) and computed tomography (CT) imaging capabilities, an alliance of cancer diagnosis and therapy has been achieved.
authors.affiliation: Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China.
authors.forename: Jiating
authors.initials: J
authors.lastname: Xu
authors.affiliation: Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China.
authors.forename: Ruichan
authors.initials: R
authors.lastname: Lv
authors.affiliation: Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China. Electronic address: yangpiaoping@hrbeu.edu.cn.
authors.forename: Piaoping
authors.initials: P
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China.
authors.forename: Huiting
authors.initials: H
authors.lastname: Bi
authors.affiliation: Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.affiliation: Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China.
authors.forename: Yunlu
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China.
authors.forename: Shili
authors.initials: S
authors.lastname: Gai
authors.affiliation: Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: He
authors.affiliation: School of Physical & Mathematical Sciences, Nanyang Technological University, Singapore.
authors.forename: Bengang
authors.initials: B
authors.lastname: Xing
authors.affiliation: State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China. Electronic address: jlin@ciac.ac.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D007259:Infrared Rays; D049449:Luminescence; D008299:Maleic Anhydrides / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D017785:Photons; D011073:Polyamines / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013387:Succinic Anhydrides / Q000737:chemistry; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D008299:Maleic Anhydrides; D011073:Polyamines; D011355:Prodrugs; D013387:Succinic Anhydrides; C063994:polyallylamine; C007474:2,3-dimethylmaleic anhydride; C031801:succinic anhydride; D002945:Cisplatin
keywords: Bioimaging; Charge convertibility; NIR photon; Pt(IV) prodrug; Upconversion