Multifunctional Nanocomposites for Targeted, Photothermal, and Chemotherapy

Ming Zhang, Fan Wu, Wentao Wang, Jian Shen, Ninglin Zhou, Changzhu Wu

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Abstract

In the past decades, advances in nanoparticles (NPs) synthesis and engineering have greatly propelled the application of nanoscale agents for therapeutic and diagnostic functions, promoting an emerging field of "nanotheranostics". In particular, they are being increasingly exploited for cancer management, in which diagnosis and therapy are combined to address clinical challenges. In this work, core-shell-structured amorphous zinc oxide (a-ZnO) on gold NPs (Au-His@a-ZnO) was produced using histidine (His) to control the shell growth under hydrothermal conditions. Subsequently, Au-His@a-ZnO NPs were integrated onto the planar structure of PEGylated graphene oxide (PEG-GO) via carbodiimide cross-linker chemistry. More importantly, strong absorption and near-infrared (NIR) emission in the range of 700 to 900 nm was observed with preferential uptake at tumors and high photothermal conversion efficiency (η = 38%). Both in vitro and in vivo studies showed that the GO@Au-His@a-ZnO NCs were biocompatible with low toxicity. Moreover, GO@Au-His@a-ZnO NCs were further conjugated with the antibody of epidermal growth factor receptor aptamer (anti-EGFR Apt) and doxorubicin (DOX), yielding Apt@GO@Au-His@a-ZnO@DOX NCs, which were then applied toward the synergetic treatment of lung cancer. The prepared Apt@GO@Au-His@a-ZnO@DOX NCs showed a high loading capacity of DOX, as well as NIR/pH-sensitive drug release in which the metal-drug complex dissociated to release antitumor Zn 2+ ions into the acidic endosome/lysosome. In addition, these materials also showed good biostability and anti-EGFR Apt-promoted binding specificity for lung cancer cells. The specific binding facilitated the cellular uptake into EGFR-mutated cancer sites, as compared with nontargeted controls. In particular, human pulmonary adenocarcinoma cell (A549)-tumor bearing mice were selected as the animal model, and efficient targeted drug delivery and the high anticancer efficacy of Apt@GO@Au-His@a-ZnO NCs in vivo were demonstrated. Taken together, our multifunctional NCs, Apt@GO@Au-His@a-ZnO@DOX NCs, have shown high efficacy in targeted, photothermal, and chemotherapy when applied to lung cancer. This proof-of-principle example suggests a fascinating perspective for these functional NCs for future clinical use.

Original languageEnglish
JournalChemistry of Materials
Volume31
Issue number6
Pages (from-to)1847-1859
ISSN0897-4756
DOIs
Publication statusPublished - 26. Mar 2019

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Zinc Oxide
Chemotherapy
Zinc oxide
Histidine
Nanocomposites
Doxorubicin
Nanoparticles
Epidermal Growth Factor Receptor
Antibodies
Tumors
Bearings (structural)
Infrared radiation
Carbodiimides
Graphite
Gold
Pharmaceutical Preparations
Oxides
Graphene
Conversion efficiency
Toxicity

Cite this

Zhang, Ming ; Wu, Fan ; Wang, Wentao ; Shen, Jian ; Zhou, Ninglin ; Wu, Changzhu. / Multifunctional Nanocomposites for Targeted, Photothermal, and Chemotherapy. In: Chemistry of Materials. 2019 ; Vol. 31, No. 6. pp. 1847-1859.
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abstract = "In the past decades, advances in nanoparticles (NPs) synthesis and engineering have greatly propelled the application of nanoscale agents for therapeutic and diagnostic functions, promoting an emerging field of {"}nanotheranostics{"}. In particular, they are being increasingly exploited for cancer management, in which diagnosis and therapy are combined to address clinical challenges. In this work, core-shell-structured amorphous zinc oxide (a-ZnO) on gold NPs (Au-His@a-ZnO) was produced using histidine (His) to control the shell growth under hydrothermal conditions. Subsequently, Au-His@a-ZnO NPs were integrated onto the planar structure of PEGylated graphene oxide (PEG-GO) via carbodiimide cross-linker chemistry. More importantly, strong absorption and near-infrared (NIR) emission in the range of 700 to 900 nm was observed with preferential uptake at tumors and high photothermal conversion efficiency (η = 38{\%}). Both in vitro and in vivo studies showed that the GO@Au-His@a-ZnO NCs were biocompatible with low toxicity. Moreover, GO@Au-His@a-ZnO NCs were further conjugated with the antibody of epidermal growth factor receptor aptamer (anti-EGFR Apt) and doxorubicin (DOX), yielding Apt@GO@Au-His@a-ZnO@DOX NCs, which were then applied toward the synergetic treatment of lung cancer. The prepared Apt@GO@Au-His@a-ZnO@DOX NCs showed a high loading capacity of DOX, as well as NIR/pH-sensitive drug release in which the metal-drug complex dissociated to release antitumor Zn 2+ ions into the acidic endosome/lysosome. In addition, these materials also showed good biostability and anti-EGFR Apt-promoted binding specificity for lung cancer cells. The specific binding facilitated the cellular uptake into EGFR-mutated cancer sites, as compared with nontargeted controls. In particular, human pulmonary adenocarcinoma cell (A549)-tumor bearing mice were selected as the animal model, and efficient targeted drug delivery and the high anticancer efficacy of Apt@GO@Au-His@a-ZnO NCs in vivo were demonstrated. Taken together, our multifunctional NCs, Apt@GO@Au-His@a-ZnO@DOX NCs, have shown high efficacy in targeted, photothermal, and chemotherapy when applied to lung cancer. This proof-of-principle example suggests a fascinating perspective for these functional NCs for future clinical use.",
author = "Ming Zhang and Fan Wu and Wentao Wang and Jian Shen and Ninglin Zhou and Changzhu Wu",
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Multifunctional Nanocomposites for Targeted, Photothermal, and Chemotherapy. / Zhang, Ming; Wu, Fan; Wang, Wentao; Shen, Jian; Zhou, Ninglin; Wu, Changzhu.

In: Chemistry of Materials, Vol. 31, No. 6, 26.03.2019, p. 1847-1859.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Multifunctional Nanocomposites for Targeted, Photothermal, and Chemotherapy

AU - Zhang, Ming

AU - Wu, Fan

AU - Wang, Wentao

AU - Shen, Jian

AU - Zhou, Ninglin

AU - Wu, Changzhu

N1 - Published online 11 June 2018

PY - 2019/3/26

Y1 - 2019/3/26

N2 - In the past decades, advances in nanoparticles (NPs) synthesis and engineering have greatly propelled the application of nanoscale agents for therapeutic and diagnostic functions, promoting an emerging field of "nanotheranostics". In particular, they are being increasingly exploited for cancer management, in which diagnosis and therapy are combined to address clinical challenges. In this work, core-shell-structured amorphous zinc oxide (a-ZnO) on gold NPs (Au-His@a-ZnO) was produced using histidine (His) to control the shell growth under hydrothermal conditions. Subsequently, Au-His@a-ZnO NPs were integrated onto the planar structure of PEGylated graphene oxide (PEG-GO) via carbodiimide cross-linker chemistry. More importantly, strong absorption and near-infrared (NIR) emission in the range of 700 to 900 nm was observed with preferential uptake at tumors and high photothermal conversion efficiency (η = 38%). Both in vitro and in vivo studies showed that the GO@Au-His@a-ZnO NCs were biocompatible with low toxicity. Moreover, GO@Au-His@a-ZnO NCs were further conjugated with the antibody of epidermal growth factor receptor aptamer (anti-EGFR Apt) and doxorubicin (DOX), yielding Apt@GO@Au-His@a-ZnO@DOX NCs, which were then applied toward the synergetic treatment of lung cancer. The prepared Apt@GO@Au-His@a-ZnO@DOX NCs showed a high loading capacity of DOX, as well as NIR/pH-sensitive drug release in which the metal-drug complex dissociated to release antitumor Zn 2+ ions into the acidic endosome/lysosome. In addition, these materials also showed good biostability and anti-EGFR Apt-promoted binding specificity for lung cancer cells. The specific binding facilitated the cellular uptake into EGFR-mutated cancer sites, as compared with nontargeted controls. In particular, human pulmonary adenocarcinoma cell (A549)-tumor bearing mice were selected as the animal model, and efficient targeted drug delivery and the high anticancer efficacy of Apt@GO@Au-His@a-ZnO NCs in vivo were demonstrated. Taken together, our multifunctional NCs, Apt@GO@Au-His@a-ZnO@DOX NCs, have shown high efficacy in targeted, photothermal, and chemotherapy when applied to lung cancer. This proof-of-principle example suggests a fascinating perspective for these functional NCs for future clinical use.

AB - In the past decades, advances in nanoparticles (NPs) synthesis and engineering have greatly propelled the application of nanoscale agents for therapeutic and diagnostic functions, promoting an emerging field of "nanotheranostics". In particular, they are being increasingly exploited for cancer management, in which diagnosis and therapy are combined to address clinical challenges. In this work, core-shell-structured amorphous zinc oxide (a-ZnO) on gold NPs (Au-His@a-ZnO) was produced using histidine (His) to control the shell growth under hydrothermal conditions. Subsequently, Au-His@a-ZnO NPs were integrated onto the planar structure of PEGylated graphene oxide (PEG-GO) via carbodiimide cross-linker chemistry. More importantly, strong absorption and near-infrared (NIR) emission in the range of 700 to 900 nm was observed with preferential uptake at tumors and high photothermal conversion efficiency (η = 38%). Both in vitro and in vivo studies showed that the GO@Au-His@a-ZnO NCs were biocompatible with low toxicity. Moreover, GO@Au-His@a-ZnO NCs were further conjugated with the antibody of epidermal growth factor receptor aptamer (anti-EGFR Apt) and doxorubicin (DOX), yielding Apt@GO@Au-His@a-ZnO@DOX NCs, which were then applied toward the synergetic treatment of lung cancer. The prepared Apt@GO@Au-His@a-ZnO@DOX NCs showed a high loading capacity of DOX, as well as NIR/pH-sensitive drug release in which the metal-drug complex dissociated to release antitumor Zn 2+ ions into the acidic endosome/lysosome. In addition, these materials also showed good biostability and anti-EGFR Apt-promoted binding specificity for lung cancer cells. The specific binding facilitated the cellular uptake into EGFR-mutated cancer sites, as compared with nontargeted controls. In particular, human pulmonary adenocarcinoma cell (A549)-tumor bearing mice were selected as the animal model, and efficient targeted drug delivery and the high anticancer efficacy of Apt@GO@Au-His@a-ZnO NCs in vivo were demonstrated. Taken together, our multifunctional NCs, Apt@GO@Au-His@a-ZnO@DOX NCs, have shown high efficacy in targeted, photothermal, and chemotherapy when applied to lung cancer. This proof-of-principle example suggests a fascinating perspective for these functional NCs for future clinical use.

U2 - 10.1021/acs.chemmater.8b00934

DO - 10.1021/acs.chemmater.8b00934

M3 - Journal article

VL - 31

SP - 1847

EP - 1859

JO - Chemistry of Materials

JF - Chemistry of Materials

SN - 0897-4756

IS - 6

ER -