Targeted Multifunctional Nanoplatform for Imaging-Guided Precision Diagnosis and Photothermal/Photodynamic Therapy of Orthotopic Hepatocellular Carcinoma

Shuo Qi; Gongyuan Liu; Jiangbo Chen; Peng Cao; Xiaohua Lei; Chengming Ding; Guodong Chen; Yachao Zhang; Lidai Wang

doi:10.2147/IJN.S377080

Targeted Multifunctional Nanoplatform for Imaging-Guided Precision Diagnosis and Photothermal/Photodynamic Therapy of Orthotopic Hepatocellular Carcinoma

Int J Nanomedicine. 2022 Aug 30:17:3777-3792. doi: 10.2147/IJN.S377080. eCollection 2022.

Authors

Shuo Qi^#^{1

2

3}, Gongyuan Liu⁴, Jiangbo Chen^{2

3}, Peng Cao¹, Xiaohua Lei¹, Chengming Ding¹, Guodong Chen^#¹, Yachao Zhang^{2

3}, Lidai Wang^{2

3}

Affiliations

¹ Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, People's Republic of China.
² Department of Biomedical Engineering, City University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
³ Department of Biomedical Engineering, City University of Hong Kong Shenzhen Research Institute, Shenzhen, People's Republic of China.
⁴ Department of Chemistry, City University of Hong Kong, Hong Kong Special Administrative Region, Peoples's Republic of China.

^# Contributed equally.

Abstract

Background: Effective theranostic of hepatocellular carcinoma (HCC) in an early-stage is imminently demanded to improve its poor prognosis. Combination of the near-infrared (NIR) photoacoustic imaging (PAI) and fluorescence imaging (FLI) can provide high temporospatial resolution, outstanding optical contrast, and deep penetration and thus is promising for accurate and sensitive HCC diagnosis.

Methods: A versatile CXCR4-targeted Indocyanine green (ICG)/Platinum (Pt)-doped polydopamine melanin-mimic nanoparticle (designated ICG/Pt@PDA-CXCR4, referred to as IPP-c) is synthesized as an HCC-specific contrast agent for high-resolution precise diagnostic PAI/FLI and optical imaging-guided targeted photothermal therapy (PTT)/photodynamic therapy (PDT) of orthotopic small hepatocellular carcinoma (SHCC).

Results: The multifunctional targeted nanoparticle yields superior HCC specificity, high imaging contrast in both PAI and FLI, good stability, reliable biocompatibility, effective singlet oxygen generation and superior photothermal conversion efficiency (PCE, 58.7%) upon 808-nm laser irradiation. The targeting ability of IPP-c was validated in in vitro experiments on selectively killing the CXCR4-overexpressing HCC cells. Moreover, we test the efficient dual-modal optical precision diagnosis properties of IPP-c via in vivo experiments on targeted particle accumulation in an early-stage SHCC mouse model (tumor diameter about 1.2 mm). Then, under the guidance of real-time optical imaging, effective and mini-invasive PTT/PDT of orthotopic SHCCs were demonstrated without damaging adjacent liver tissues or other major organs.

Conclusion: This study presented a multifunctional CXCR4-targeted nanoparticle to conduct effective and mini-invasive phototherapeutics of orthotopic SHCCs via the real-time quantitative guidance by optical imaging, which provided a new perception for building a versatile targeted nanoplatform for phototheranostics of early-stage HCC.

Keywords: CXCR4-targeted; hepatocellular carcinoma; photoacoustic imaging; photodynamic therapy; photothermal therapy.

MeSH terms

Animals
Carcinoma, Hepatocellular* / diagnostic imaging
Carcinoma, Hepatocellular* / drug therapy
Indocyanine Green / pharmacology
Liver Neoplasms* / diagnostic imaging
Liver Neoplasms* / therapy
Mice
Photochemotherapy*
Phototherapy / methods
Photothermal Therapy
Theranostic Nanomedicine / methods

Substances

Indocyanine Green