title: Inducing Optimal Antitumor Immune Response through Coadministering iRGD with Pirarubicin Loaded Nanostructured Lipid Carriers for Breast Cancer Therapy.
abstract: Chemotherapeutic agents trigger antitumor immune response through inducing immunogenic tumor cell death. However, severe toxicity to immune system and insufficient immunogenic cell death hinder chemotherapy from arousing efficient antitumor immunity in vivo. In this study, the cytotoxic drug, pirarubicin (THP), was entrapped into nanostructured lipid carriers (NLC); THP-NLC significantly reduced the toxicity of THP to immune system and improved immune status of breast cancer bearing mice. When THP-NLC was coinjected with iRGD (a tumor-penetrating peptide), drug accumulation in tumors was greatly elevated, which led to significant control of tumor growth and increase of immunogenic tumor cell death. Subsequently, the cytotoxic T lymphocytes (CD3+and CD8+cells) infiltration and cytokine (IFN-γ and INF-α) secretion in tumors were heavily increased. The efficient T-cell dependent control of tumors in the late stage and the lower side effects contributed to the longest whole survival of THP-NLC + iRGD treated mice. Therefore, the coadministration of THP-NLC with iRGD resulted in increased tumor cell direct-killing death and enhanced antitumor immune response. Our results illustrated that THP could serve as an immunogenic cell death inducer and the proposed drug delivery strategy might impact cancer immunotherapy by arousing increased immunogenic tumor cell death.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Deng
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
authors.forename: Mengdi
authors.initials: M
authors.lastname: Jia
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
authors.forename: Guangfei
authors.initials: G
authors.lastname: Wei
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Tan
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
authors.forename: Huile
authors.identifier: 0000-0002-5355-7238
authors.initials: H
authors.lastname: Gao
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
authors.forename: Xun
authors.identifier: 0000-0002-4671-352X
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.|School of Pharmacy, Chengdu Medical College , Chengdu 610083, China.
authors.forename: Quan
authors.initials: Q
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 610041, China.
authors.forename: Tao
authors.identifier: 0000-0002-9866-9911
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 610041, China.
authors.forename: Zhirong
authors.identifier: 0000-0001-9118-5394
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D007109:Immunity / Q000187:drug effects*; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000008:administration & dosage*; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects
chemical_list: D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; C569656:N-end cysteine peptide tumor-homing peptide; D009842:Oligopeptides; D004317:Doxorubicin; C027260:pirarubicin
keywords: anthracyclines; antitumor immune response; iRGD; immunogenic tumor cell death; nanostructured lipid carriers; targeted chemotherapy