Persistent Regulation of Tumor Hypoxia Microenvironment via a Bioinspired Pt-Based Oxygen Nanogenerator for Multimodal Imaging-Guided Synergistic Phototherapy.

Abstract

Multifunctional nanoplatforms for imaging-guided synergistic antitumor treatment are highly desirable in biomedical applications. However, anticancer treatment is largely affected by the pre-existing hypoxic tumor microenvironment (TME), which not only causes the resistance of the tumors to photodynamic therapy (PDT), but also promotes tumorigenesis and tumor progression. Here, a continuous O2 self-enriched nanoplatform is constructed for multimodal imaging-guided synergistic phototherapy based on octahedral gold nanoshells (GNSs), which are constructed by a more facile and straightforward one-step method using platinum (Pt) nanozyme-decorated metal-organic frameworks (MOF) as the inner template. The Pt-decorated MOF@GNSs (PtMGs) are further functionalized with human serum albumin-chelated gadolinium (HSA-Gd, HGd) and loaded with indocyanine green (ICG) (ICG-PtMGs@HGd) to achieve a synergistic PDT/PTT effect and fluorescence (FL)/multispectral optoacoustic tomography (MSOT)/X-ray computed tomography (CT)/magnetic resonance (MR) imaging. The Pt-decorated nanoplatform endows remarkable catalase-like behavior and facilitates the continuous decomposition of the endogenous H2O2 into O2 to enhance the PDT effect under hypoxic TME. HSA modification enhances the biocompatibility and tumor-targeting ability of the nanocomposites. This TME-responsive and O2 self-supplement nanoparticle holds great potential as a multifunctional theranostic nanoplatform for the multimodal imaging-guided synergistic phototherapy of solid tumors.

• Authors: Qing You, Kaiyue Zhang, Jingyi Liu, Changliang Liu, Huayi Wang, Mengting Wang, Siyuan Ye, Houqian Gao, Letian Lv, Chen Wang, Ling Zhu, Yanlian Yang
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 7 Issue 17 Pg. 1903341 (Sep 2020) ISSN: 2198-3844 [Print] Germany
• PMID: 32995114 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors. Published by Wiley‐VCH GmbH.