CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells

Shujing Liang; Chao Li; Chunlei Zhang; Yunsheng Chen; Liang Xu; Chenchen Bao; Xiaoyong Wang; Gang Liu; Fengchun Zhang; Daxiang Cui

doi:10.7150/thno.11632

CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells

Theranostics. 2015 Jun 1;5(9):970-84. doi: 10.7150/thno.11632. eCollection 2015.

Authors

Shujing Liang¹, Chao Li², Chunlei Zhang², Yunsheng Chen², Liang Xu³, Chenchen Bao², Xiaoyong Wang⁴, Gang Liu⁴, Fengchun Zhang⁵, Daxiang Cui²

Affiliations

¹ 1. Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China ; 2. Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Department of Instrument Science and Engineering, Research Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
² 2. Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Department of Instrument Science and Engineering, Research Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
³ 1. Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China.
⁴ 3. Center for molecular imaging and Translational medicine of Xiamen University, Xiamen 361102, P. R. China.
⁵ 1. Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China ; 4. Suzhou Kowloon Hospital Shanghai Jiaotong University School of Medicine.

Abstract

Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm(2), 5 min) in vitro experiment. Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established. Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed. Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post-injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice. The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future.

Keywords: CD44v6 monoclonal antibody; gastric cancer stem cells (GCSCs); gold nanostars; photoacoustic imaging; photothermal therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / administration & dosage
Antibodies, Monoclonal / pharmacokinetics*
Disease Models, Animal
Drug Delivery Systems / methods*
Gold / administration & dosage
Gold / pharmacokinetics*
Humans
Hyaluronan Receptors / immunology*
Hyperthermia, Induced / methods*
Infrared Rays
Low-Level Light Therapy
Mice, Nude
Nanoparticles / administration & dosage
Optical Imaging / methods
Photoacoustic Techniques / methods*
Stomach Neoplasms / diagnosis
Stomach Neoplasms / drug therapy*
Survival Analysis
Theranostic Nanomedicine / methods
Treatment Outcome

Substances

Antibodies, Monoclonal
CD44v6 antigen
Hyaluronan Receptors
Gold

Grants and funding

F31 AA020700/AA/NIAAA NIH HHS/United States