title: Enhanced antitumor effects by docetaxel/LL37-loaded thermosensitive hydrogel nanoparticles in peritoneal carcinomatosis of colorectal cancer.
abstract: Intraperitoneal chemotherapy was explored in clinical trials as a promising strategy to improve the therapeutic effects of chemotherapy. In this work, we developed a biodegradable and injectable drug-delivery system by coencapsulation of docetaxel (Doc) and LL37 peptide polymeric nanoparticles (Doc+LL37 NPs) in a thermosensitive hydrogel system for colorectal peritoneal carcinoma therapy. Firstly, polylactic acid (PLA)-Pluronic L35-PLA (PLA-L35-PLA) was explored to prepare the biodegradable Doc+LL37 NPs using a water-in-oil-in-water double-emulsion solvent-evaporation method. Then, biodegradable and injectable thermosensitive PLA-L64-PLA hydrogel with lower sol-gel transition temperature at around body temperature was also prepared. Transmission electron microscopy revealed that the Doc+LL37 NPs formed with the PLA-L35-PLA copolymer were spherical. Fourier-transform infrared spectra certified that Doc and LL37 were encapsulated successfully. X-ray diffraction diagrams indicated that Doc was encapsulated amorphously. Intraperitoneal administration of Doc+LL37 NPs-hydrogel significantly suppressed the growth of HCT116 peritoneal carcinomatosis in vivo and prolonged the survival of tumor-bearing mice. Our results suggested that Doc+LL37 NPs-hydrogel may have potential clinical applications.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Rangrang
authors.initials: R
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Lan
authors.initials: L
authors.lastname: Mei
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Liangxue
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, and Collaborative Innovation Center for Biotherapy, Beijing, People's Republic of China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: You
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D054804:Cathelicidins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D053938:DNA Fragmentation / Q000187:drug effects; D000077143:Docetaxel; D005455:Fluorescent Antibody Technique; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007274:Injections, Intraperitoneal; D019344:Lactic Acid / Q000737:chemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D054804:Cathelicidins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011091:Polyesters; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D019344:Lactic Acid; C033616:poly(lactide)
keywords: coencapsulation; hydrogel; injectable; intraperitoneal chemotherapy; nanoparticles