In vitro characterization and cellular uptake profiles of TAMs-targeted lipid calcium carbonate nanoparticles for cancer immunotherapy

Tumor-associated macrophages (TAMs) are key contributors to tumor development, accelerated tumor invasion and metastasis, and induction of immunosuppression. Targeted delivery of immunomodulatory agents to promote polarization of TAMs may alleviate the immunosuppressive tumor microenvironment. Calci...

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Main Authors: Xiaoyan Xu, Renjie Li, Runqi Dong, Yanfang Yang, Hongliang Wang, Jialing Cheng, Yuling Liu, Jun Ye
Format: Article
Language:English
Published: Compuscript Ltd 2022-10-01
Series:Acta Materia Medica
Subjects:
Online Access:https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2022-0030
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author Xiaoyan Xu
Renjie Li
Runqi Dong
Yanfang Yang
Hongliang Wang
Jialing Cheng
Yuling Liu
Jun Ye
author_facet Xiaoyan Xu
Renjie Li
Runqi Dong
Yanfang Yang
Hongliang Wang
Jialing Cheng
Yuling Liu
Jun Ye
author_sort Xiaoyan Xu
collection DOAJ
description Tumor-associated macrophages (TAMs) are key contributors to tumor development, accelerated tumor invasion and metastasis, and induction of immunosuppression. Targeted delivery of immunomodulatory agents to promote polarization of TAMs may alleviate the immunosuppressive tumor microenvironment. Calcium carbonate nanoparticles (CCN), which exhibit excellent biocompatibility, pH sensitivity, and easy surface modification, have attracted substantial attention in targeted nano delivery. In this study, CCN were used as a matrix material to develop UNO-peptide-modified lipid CCN for targeted immunomodulation of TAMs by using the mannose receptor overexpressed on the surfaces of TAMs as targets. The preparation of CCN was optimized through single-factor testing with the gas diffusion method with the particle size as the index. The surface modification of CCN with UNO-peptide-modified phospholipids was performed, and its targeting effect on TAMs was investigated. The average particle size of the CCN and UNO-peptide-modified CCN was 144.5 ± 3.8 nm and 167.0 ± 1.3 nm, respectively. UNO-peptide-modified CCN entered TAMs via actively targeted uptake mediated by mannose receptors. Our results demonstrated that the developed UNO-peptide-modified CCN with controlled nano-size and excellent TAMs-targeting properties is a highly promising nanocarrier for targeted delivery of TAM immunomodulatory agents.
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spelling doaj.art-a499d175773f4bc399c6a3cc8ca348ac2023-09-26T08:59:45ZengCompuscript LtdActa Materia Medica2737-79462022-10-011340041010.15212/AMM-2022-0030In vitro characterization and cellular uptake profiles of TAMs-targeted lipid calcium carbonate nanoparticles for cancer immunotherapyXiaoyan Xu0Renjie Li1Runqi Dong2Yanfang Yang3Hongliang Wang4Jialing Cheng5Yuling Liu6Jun Ye7State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. ChinaCapital Normal University High School, Beijing 100048, P.R. ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. ChinaTumor-associated macrophages (TAMs) are key contributors to tumor development, accelerated tumor invasion and metastasis, and induction of immunosuppression. Targeted delivery of immunomodulatory agents to promote polarization of TAMs may alleviate the immunosuppressive tumor microenvironment. Calcium carbonate nanoparticles (CCN), which exhibit excellent biocompatibility, pH sensitivity, and easy surface modification, have attracted substantial attention in targeted nano delivery. In this study, CCN were used as a matrix material to develop UNO-peptide-modified lipid CCN for targeted immunomodulation of TAMs by using the mannose receptor overexpressed on the surfaces of TAMs as targets. The preparation of CCN was optimized through single-factor testing with the gas diffusion method with the particle size as the index. The surface modification of CCN with UNO-peptide-modified phospholipids was performed, and its targeting effect on TAMs was investigated. The average particle size of the CCN and UNO-peptide-modified CCN was 144.5 ± 3.8 nm and 167.0 ± 1.3 nm, respectively. UNO-peptide-modified CCN entered TAMs via actively targeted uptake mediated by mannose receptors. Our results demonstrated that the developed UNO-peptide-modified CCN with controlled nano-size and excellent TAMs-targeting properties is a highly promising nanocarrier for targeted delivery of TAM immunomodulatory agents.https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2022-0030calcium carbonate nanoparticlestumor-associated macrophagescancer immunotherapytargeted delivery
spellingShingle Xiaoyan Xu
Renjie Li
Runqi Dong
Yanfang Yang
Hongliang Wang
Jialing Cheng
Yuling Liu
Jun Ye
In vitro characterization and cellular uptake profiles of TAMs-targeted lipid calcium carbonate nanoparticles for cancer immunotherapy
Acta Materia Medica
calcium carbonate nanoparticles
tumor-associated macrophages
cancer immunotherapy
targeted delivery
title In vitro characterization and cellular uptake profiles of TAMs-targeted lipid calcium carbonate nanoparticles for cancer immunotherapy
title_full In vitro characterization and cellular uptake profiles of TAMs-targeted lipid calcium carbonate nanoparticles for cancer immunotherapy
title_fullStr In vitro characterization and cellular uptake profiles of TAMs-targeted lipid calcium carbonate nanoparticles for cancer immunotherapy
title_full_unstemmed In vitro characterization and cellular uptake profiles of TAMs-targeted lipid calcium carbonate nanoparticles for cancer immunotherapy
title_short In vitro characterization and cellular uptake profiles of TAMs-targeted lipid calcium carbonate nanoparticles for cancer immunotherapy
title_sort in vitro characterization and cellular uptake profiles of tams targeted lipid calcium carbonate nanoparticles for cancer immunotherapy
topic calcium carbonate nanoparticles
tumor-associated macrophages
cancer immunotherapy
targeted delivery
url https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2022-0030
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