title: Tailoring polymeric hybrid micelles with lymph node targeting ability to improve the potency of cancer vaccines.
abstract: It has been widely accepted that lymph nodes (LNs) are critical targets of cancer vaccines and particles sized between 10 and 100 nm with a neutral or negative surface charge are preferred for lymphatic transfer after subcutaneous or intradermal injection. However their limited uptake by antigen presenting cells (APCs) and inadequate retention within LNs undoubtedly restrains their strength on activating T cell immunity. Here, we address this issue by tailoring the physicochemical properties of polymeric hybrid micelles (HMs), which are self-assembled from two amphiphilic diblock copolymers, poly-(ethylene glycol) phosphorethanolamine (PEG-PE) and polyethylenimine-stearic acid conjugate (PSA) via hydrophobic and electrostatic interactions. We successfully encapsulate melanoma antigen peptide Trp2 and Toll-like receptor-9 (TLR-9) agonist CpG ODN into HMs with a size of sub-30 nm. Their surface characteristics which are found closely related to their in vivo kinetics can be modulated by simply adjusting the molar ratio of PEG-PE and PSA. Our results demonstrated the optimized HMs with an equal mol of PEG-PE and PSA can potently target proximal LNs where their cargos are efficiently internalized by DCs. Furthermore, HMs mediated Trp2/CpG delivery system greatly expands antigen specific cytotoxic T lymphocytes (CTLs) and offers a strong anti-tumor effect in a lung metastatic melanoma model.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu No. 17 Section, 3 Renmin South Rd, Chengdu, 610041, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu No. 17 Section, 3 Renmin South Rd, Chengdu, 610041, PR China.
authors.forename: Hanmei
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu No. 17 Section, 3 Renmin South Rd, Chengdu, 610041, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu No. 17 Section, 3 Renmin South Rd, Chengdu, 610041, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Yu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu No. 17 Section, 3 Renmin South Rd, Chengdu, 610041, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu No. 17 Section, 3 Renmin South Rd, Chengdu, 610041, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Ke
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu No. 17 Section, 3 Renmin South Rd, Chengdu, 610041, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu No. 17 Section, 3 Renmin South Rd, Chengdu, 610041, PR China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu No. 17 Section, 3 Renmin South Rd, Chengdu, 610041, PR China. Electronic address: sunxun@scu.edu.cn.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D004655:Emulsions / Q000737:chemistry; D005260:Female; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D008198:Lymph Nodes / Q000737:chemistry / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004655:Emulsions; D008823:Micelles; D053769:Nanocapsules; D011108:Polymers
keywords: Cytotoxic T lymphocytes; Lymph node; Melanoma; Polymeric hybrid micelles; Targeting; Vaccine