Lipid‐Peptide‐mRNA Nanoparticles Augment Radioiodine Uptake in Anaplastic Thyroid Cancer

Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC). For more efficient delivery of messenger RNA (mRNA) to manipulate protein expression, a lipid‐peptide‐mRNA (LPm) nanoparticle (NP) is developed. The L...

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Published inAdvanced science Vol. 10; no. 3; pp. e2204334 - n/a
Main Authors Li, Qinglin, Zhang, Lizhuo, Lang, Jiayan, Tan, Zhuo, Feng, Qingqing, Zhu, Fei, Liu, Guangna, Ying, Zhangguo, Yu, Xuefei, Feng, He, Yi, Heqing, Wen, Qingliang, Jin, Tiefeng, Cheng, Keman, Zhao, Xiao, Ge, Minghua
Format Journal Article
LanguageEnglish
Published Germany John Wiley & Sons, Inc 01.01.2023
John Wiley and Sons Inc
Wiley
Subjects
Acids
anaplastic thyroid carcinoma
Animals
Cancer therapies
Cell Line, Tumor
Efficiency
Gene expression
Humans
Iodine
Iodine Radioisotopes - therapeutic use
Lipids
lipid‐peptide‐mRNA nanoparticles
Liposomes
Lymphatic system
Medical prognosis
Mice
Mice, Nude
mRNA delivery
Nanoparticles
Peptides
Protein expression
Proteins
RNA, Messenger
sodium iodide transporter
Statistical significance
Thyroid cancer
Thyroid Carcinoma, Anaplastic - genetics
Thyroid Carcinoma, Anaplastic - metabolism
Thyroid Carcinoma, Anaplastic - therapy
Thyroid Neoplasms - genetics
Thyroid Neoplasms - radiotherapy
Tumors
anaplastic thyroid carcinoma
lipid-peptide-mRNA nanoparticles
mRNA delivery
sodium iodide transporter
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Abstract Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC). For more efficient delivery of messenger RNA (mRNA) to manipulate protein expression, a lipid‐peptide‐mRNA (LPm) nanoparticle (NP) is developed. The LPm NP is prepared by using amphiphilic peptides to assemble a peptide core and which is then coated with cationic lipids. An amphiphilic chimeric peptide, consisting of nine arginine and hydrophobic segments (6 histidine, C18 or cholesterol), is synthesized for adsorption of mRNA encoding NIS in RNase‐free conditions. In vitro studies show that LP(R9H6) m NP is most efficient at delivering mRNA and can increase NIS expression in ATC cells by more than 10‐fold. After intratumoral injection of NIS mRNA formulated in optimized LPm NP, NIS expression in subcutaneous ATC tumor tissue increases significantly in nude mice, resulting in more iodine 131 (131I) accumulation in the tumor, thereby significantly inhibiting tumor growth. Overall, this work designs three arginine‐rich peptide nanoparticles, contributing to the choice of liposome cores for gene delivery. LPm NP can serve as a promising adjunctive therapy for patients with ATC by restoring iodine affinity and enhancing the therapeutic efficacy of radioactive iodine. Lipid‐peptide‐mRNA (LPm) nanoparticles (NPs), is employed to deliver mRNA. mRNA encoding sodium iodide symporter (NIS) delivered by LPm NPs significantly augment the expression of NIS protein on the cell membrane of anaplastic thyroid cancer (ATC) in vivo and in vitro. NIS‐mRNA LPm NPs combining 131I therapy heightens intracellular aggregation of 131I and antitumor effect.
AbstractList Abstract Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC). For more efficient delivery of messenger RNA (mRNA) to manipulate protein expression, a lipid‐peptide‐mRNA (LPm) nanoparticle (NP) is developed. The LPm NP is prepared by using amphiphilic peptides to assemble a peptide core and which is then coated with cationic lipids. An amphiphilic chimeric peptide, consisting of nine arginine and hydrophobic segments (6 histidine, C18 or cholesterol), is synthesized for adsorption of mRNA encoding NIS in RNase‐free conditions. In vitro studies show that LP(R9H6) m NP is most efficient at delivering mRNA and can increase NIS expression in ATC cells by more than 10‐fold. After intratumoral injection of NIS mRNA formulated in optimized LPm NP, NIS expression in subcutaneous ATC tumor tissue increases significantly in nude mice, resulting in more iodine 131 (131I) accumulation in the tumor, thereby significantly inhibiting tumor growth. Overall, this work designs three arginine‐rich peptide nanoparticles, contributing to the choice of liposome cores for gene delivery. LPm NP can serve as a promising adjunctive therapy for patients with ATC by restoring iodine affinity and enhancing the therapeutic efficacy of radioactive iodine.
Abstract Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC). For more efficient delivery of messenger RNA (mRNA) to manipulate protein expression, a lipid‐peptide‐mRNA (LPm) nanoparticle (NP) is developed. The LPm NP is prepared by using amphiphilic peptides to assemble a peptide core and which is then coated with cationic lipids. An amphiphilic chimeric peptide, consisting of nine arginine and hydrophobic segments (6 histidine, C18 or cholesterol), is synthesized for adsorption of mRNA encoding NIS in RNase‐free conditions. In vitro studies show that LP(R9H6) m NP is most efficient at delivering mRNA and can increase NIS expression in ATC cells by more than 10‐fold. After intratumoral injection of NIS mRNA formulated in optimized LPm NP, NIS expression in subcutaneous ATC tumor tissue increases significantly in nude mice, resulting in more iodine 131 ( 131 I) accumulation in the tumor, thereby significantly inhibiting tumor growth. Overall, this work designs three arginine‐rich peptide nanoparticles, contributing to the choice of liposome cores for gene delivery. LPm NP can serve as a promising adjunctive therapy for patients with ATC by restoring iodine affinity and enhancing the therapeutic efficacy of radioactive iodine.
Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC). For more efficient delivery of messenger RNA (mRNA) to manipulate protein expression, a lipid-peptide-mRNA (LPm) nanoparticle (NP) is developed. The LPm NP is prepared by using amphiphilic peptides to assemble a peptide core and which is then coated with cationic lipids. An amphiphilic chimeric peptide, consisting of nine arginine and hydrophobic segments (6 histidine, C18 or cholesterol), is synthesized for adsorption of mRNA encoding NIS in RNase-free conditions. In vitro studies show that LP(R9H6) m NP is most efficient at delivering mRNA and can increase NIS expression in ATC cells by more than 10-fold. After intratumoral injection of NIS mRNA formulated in optimized LPm NP, NIS expression in subcutaneous ATC tumor tissue increases significantly in nude mice, resulting in more iodine 131 (131I) accumulation in the tumor, thereby significantly inhibiting tumor growth. Overall, this work designs three arginine-rich peptide nanoparticles, contributing to the choice of liposome cores for gene delivery. LPm NP can serve as a promising adjunctive therapy for patients with ATC by restoring iodine affinity and enhancing the therapeutic efficacy of radioactive iodine.
Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC). For more efficient delivery of messenger RNA (mRNA) to manipulate protein expression, a lipid-peptide-mRNA (LPm) nanoparticle (NP) is developed. The LPm NP is prepared by using amphiphilic peptides to assemble a peptide core and which is then coated with cationic lipids. An amphiphilic chimeric peptide, consisting of nine arginine and hydrophobic segments (6 histidine, C18 or cholesterol), is synthesized for adsorption of mRNA encoding NIS in RNase-free conditions. In vitro studies show that LP(R9H6) m NP is most efficient at delivering mRNA and can increase NIS expression in ATC cells by more than 10-fold. After intratumoral injection of NIS mRNA formulated in optimized LPm NP, NIS expression in subcutaneous ATC tumor tissue increases significantly in nude mice, resulting in more iodine 131 ( I) accumulation in the tumor, thereby significantly inhibiting tumor growth. Overall, this work designs three arginine-rich peptide nanoparticles, contributing to the choice of liposome cores for gene delivery. LPm NP can serve as a promising adjunctive therapy for patients with ATC by restoring iodine affinity and enhancing the therapeutic efficacy of radioactive iodine.
Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC). For more efficient delivery of messenger RNA (mRNA) to manipulate protein expression, a lipid‐peptide‐mRNA (LPm) nanoparticle (NP) is developed. The LPm NP is prepared by using amphiphilic peptides to assemble a peptide core and which is then coated with cationic lipids. An amphiphilic chimeric peptide, consisting of nine arginine and hydrophobic segments (6 histidine, C18 or cholesterol), is synthesized for adsorption of mRNA encoding NIS in RNase‐free conditions. In vitro studies show that LP(R9H6) m NP is most efficient at delivering mRNA and can increase NIS expression in ATC cells by more than 10‐fold. After intratumoral injection of NIS mRNA formulated in optimized LPm NP, NIS expression in subcutaneous ATC tumor tissue increases significantly in nude mice, resulting in more iodine 131 ( 131 I) accumulation in the tumor, thereby significantly inhibiting tumor growth. Overall, this work designs three arginine‐rich peptide nanoparticles, contributing to the choice of liposome cores for gene delivery. LPm NP can serve as a promising adjunctive therapy for patients with ATC by restoring iodine affinity and enhancing the therapeutic efficacy of radioactive iodine. Lipid‐peptide‐mRNA (LPm) nanoparticles (NPs), is employed to deliver mRNA. mRNA encoding sodium iodide symporter (NIS) delivered by LPm NPs significantly augment the expression of NIS protein on the cell membrane of anaplastic thyroid cancer (ATC) in vivo and in vitro. NIS‐mRNA LPm NPs combining 131I therapy heightens intracellular aggregation of 131I and antitumor effect.
Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC). For more efficient delivery of messenger RNA (mRNA) to manipulate protein expression, a lipid‐peptide‐mRNA (LPm) nanoparticle (NP) is developed. The LPm NP is prepared by using amphiphilic peptides to assemble a peptide core and which is then coated with cationic lipids. An amphiphilic chimeric peptide, consisting of nine arginine and hydrophobic segments (6 histidine, C18 or cholesterol), is synthesized for adsorption of mRNA encoding NIS in RNase‐free conditions. In vitro studies show that LP(R9H6) m NP is most efficient at delivering mRNA and can increase NIS expression in ATC cells by more than 10‐fold. After intratumoral injection of NIS mRNA formulated in optimized LPm NP, NIS expression in subcutaneous ATC tumor tissue increases significantly in nude mice, resulting in more iodine 131 (131I) accumulation in the tumor, thereby significantly inhibiting tumor growth. Overall, this work designs three arginine‐rich peptide nanoparticles, contributing to the choice of liposome cores for gene delivery. LPm NP can serve as a promising adjunctive therapy for patients with ATC by restoring iodine affinity and enhancing the therapeutic efficacy of radioactive iodine. Lipid‐peptide‐mRNA (LPm) nanoparticles (NPs), is employed to deliver mRNA. mRNA encoding sodium iodide symporter (NIS) delivered by LPm NPs significantly augment the expression of NIS protein on the cell membrane of anaplastic thyroid cancer (ATC) in vivo and in vitro. NIS‐mRNA LPm NPs combining 131I therapy heightens intracellular aggregation of 131I and antitumor effect.
Author Wen, Qingliang
Zhang, Lizhuo
Yi, Heqing
Yu, Xuefei
Ying, Zhangguo
Zhao, Xiao
Tan, Zhuo
Cheng, Keman
Jin, Tiefeng
Feng, Qingqing
Lang, Jiayan
Feng, He
Ge, Minghua
Zhu, Fei
Liu, Guangna
Li, Qinglin
AuthorAffiliation 2 The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Hangzhou Zhejiang 310022 China
3 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 China
1 Department of Head and Neck Surgery Center of Otolaryngology-head and neck surgery Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College) Key Laboratory of Endocrine Gland Diseases of Zhejiang Province Hangzhou Zhejiang 310014 China
4 Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences Beijing 100049 China
AuthorAffiliation_xml – name: 1 Department of Head and Neck Surgery Center of Otolaryngology-head and neck surgery Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College) Key Laboratory of Endocrine Gland Diseases of Zhejiang Province Hangzhou Zhejiang 310014 China
– name: 2 The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Hangzhou Zhejiang 310022 China
– name: 4 Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences Beijing 100049 China
– name: 3 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 China
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Issue 3
Keywords anaplastic thyroid carcinoma
lipid-peptide-mRNA nanoparticles
mRNA delivery
sodium iodide transporter
Language English
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Snippet Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC). For more...
Abstract Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC)....
Abstract Restoring sodium iodide symporter (NIS) expression and function remains a major challenge for radioiodine therapy in anaplastic thyroid cancer (ATC)....
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StartPage e2204334
SubjectTerms Acids
anaplastic thyroid carcinoma
Animals
Cancer therapies
Cell Line, Tumor
Efficiency
Gene expression
Humans
Iodine
Iodine Radioisotopes - therapeutic use
Lipids
lipid‐peptide‐mRNA nanoparticles
Liposomes
Lymphatic system
Medical prognosis
Mice
Mice, Nude
mRNA delivery
Nanoparticles
Peptides
Protein expression
Proteins
RNA, Messenger
sodium iodide transporter
Statistical significance
Thyroid cancer
Thyroid Carcinoma, Anaplastic - genetics
Thyroid Carcinoma, Anaplastic - metabolism
Thyroid Carcinoma, Anaplastic - therapy
Thyroid Neoplasms - genetics
Thyroid Neoplasms - radiotherapy
Tumors
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Title Lipid‐Peptide‐mRNA Nanoparticles Augment Radioiodine Uptake in Anaplastic Thyroid Cancer
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