title: A New Concept of Enhancing Immuno-Chemotherapeutic Effects Against B16F10 TumorviaSystemic Administration by Taking Advantages of the Limitation of EPR Effect.
abstract: The enhanced permeability and retention (EPR) effect has been comfortably accepted, and extensively assumed as a keystone in the research on tumor-targeted drug delivery system. Due to the unsatisfied tumor-targeting efficiency of EPR effect being one conspicuous drawback, nanocarriers that merely relying on EPR effect are difficult to access the tumor tissue and consequently trigger efficient tumor therapy in clinic. In the present contribution, we break up the shackles of EPR effect on nanocarriers thanks to their universal distribution characteristic. We successfully design a paclitaxel (PTX) and alpha-galactosylceramide (αGC) co-loaded TH peptide (AGYLLGHINLHHLAHL(Aib)HHIL-Cys) -modified liposome (PTX/αGC-TH-Lip) and introduce a new concept of immuno-chemotherapy combination via accumulation of these liposomes at both spleen and tumor sites naturally and simultaneously. The PTX-initiated cytotoxicity attacks tumor cells at tumor sites, meanwhile, the αGC-triggered antitumor immune response emerges at spleen tissue. Different to the case that liposomes are loaded with sole drug, in this concept two therapeutic processes effectively reinforce each other, thereby elevating the tumor therapy efficiency significantly. The data demonstrates that the PTX/αGC-TH-Lip not only possess therapeutic effect against highly malignant B16F10 melanoma tumor, but also adjust thein vivoimmune status and induce a more remarkable systemic antitumor immunity that could further suppress the growth of tumor at distant site. This work exhibits the capability of the PTX/αGC-TH-Lip in improving immune-chemotherapy against tumor after systemic administration.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Block 3, 17 Southern Renmin Road, Chengdu 610041, P. R. China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Block 3, 17 Southern Renmin Road, Chengdu 610041, P. R. China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Tai
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Block 3, 17 Southern Renmin Road, Chengdu 610041, P. R. China.
authors.forename: Kairong
authors.initials: K
authors.lastname: Shi
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Block 3, 17 Southern Renmin Road, Chengdu 610041, P. R. China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Ruan
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Block 3, 17 Southern Renmin Road, Chengdu 610041, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Block 3, 17 Southern Renmin Road, Chengdu 610041, P. R. China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of hematology, West China Hospital, Sichuan university, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, P. R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Block 3, 17 Southern Renmin Road, Chengdu 610041, P. R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005699:Galactosylceramides / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods*; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005699:Galactosylceramides; D008081:Liposomes; C493154:alpha-galactosylceramide; D017239:Paclitaxel
keywords: Alpha-galactosylceramide; Cancer immune-chemotherapy.; Distribution characteristic; Liposome; Paclitaxel