title: Bridging the Gap between Macroscale Drug Delivery Systems and Nanomedicines: A Nanoparticle-Assembled Thermosensitive Hydrogel for Peritumoral Chemotherapy.
abstract: The objective of this study was to investigate the spatiotemporal delivery of nanomedicines by an injectable, thermosensitive, and nanoparticle-self-aggregated hydrogel for peritumoral chemotherapy. Doxorubicin (Dox) was taken as the model medicine, which was encapsulated into poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT) nanoparticles (PECT/Dox NPs). Macroscale hydrogel was formed by thermosensitive self-aggregation of PECT/Dox NPs in aqueous solution. Drug release from the hydrogel formulation was dominated by sustained shedding of PECT/Dox NPs and the following drug diffusion from these NPs. The hydrogel retention and release pattern of NPs in vivo was further confirmed by fluorescence resonance energy transfer (FRET) imaging. A single treatment with the hydrogel formulation possessed similar cytotoxicity against HepG2 cells compared to triple administrations of free Dox or PECT/Dox NPs in vitro due to enhanced uptake of PECT/Dox NPs and sustained intracellular drug release. Importantly, single peritumoral injection of drug-encapsulated hydrogel in vivo showed advantages over multiple intravenous administrations of PECT/Dox NPs and free Dox, including preferential and prolonged local drug accumulation and retention in tumors, resulting in superior cancer chemotherapy efficiency. Collectively, such a unique thermosensitive and nanoparticle-shedding hydrogel could effectively combine the advantages of nanomedicines and macroscale drug delivery systems, demonstrating great potential in the local nanodrugs' delivery. It will open a new promising path for cancer chemotherapy with enhanced treatment efficacy and minimized side effects.
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300192, China.
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300192, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Song
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300192, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300192, China.
authors.forename: Jinjian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300192, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300192, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300192, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300192, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300192, China.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
mesh_terms: D004317:Doxorubicin; D016503:Drug Delivery Systems; D056945:Hep G2 Cells; D006801:Humans; D020100:Hydrogels; D050997:Nanomedicine; D053758:Nanoparticles
chemical_list: D020100:Hydrogels; D004317:Doxorubicin
keywords: doxorubicin; macroscale drug delivery system; nanomedicines; nanoparticle-assembled hydrogel; peritumoral chemotherapy