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.

Multifunctional Nanodrug Mediates Synergistic Photodynamic Therapy and MDSCs‐Targeting Immunotherapy of Colon Cancer

“…Thus, imaging‐visible LIC showed fluorescence signal distribution in spleen in ex vivo fluorescence imaging, which was also observed in other studies. [ 17 , 34 ]…”

Catalase Nanocrystals Loaded with Methylene Blue as Oxygen Self‐Supplied, Imaging‐Guided Platform for Photodynamic Therapy of Hypoxic Tumors

“…Then the solution was irradiated with 690 nm laser (50 mW cm −2 ) at predetermined time intervals (5, 10, 15, 20, 25, and 30 min), and afterward the absorption spectrum at 300-450 nm was recorded. In another experiment, H 2 O 2 (100 × 10 −6 m) was added to CatCry-MB/ABDA water suspension (in order to mimic tumor microenvironment) and the resulted mixture was irradiated with 690 nm laser (50 mW cm −2 ) at predetermined time intervals (5,10,15,20,25, and 30 min), and then the absorption spectrum at 300-450 nm was recorded. The intracellular 1 O 2 generation was visualized by the singlet oxygen detection kit (O22) and imaged with CLSM.…”

“…[8,9] Therefore, it is urgently necessary to advance O 2 supply strategies for alleviating tumor hypoxia to improve the therapeutic efficiency of PDT.The high concentration of hydrogen peroxide (H 2 O 2 ) in the tumor microenvironment brings new opportunities to design smart self-responded platform for reversing the hypoxia-associated resistance of tumors therapy. [10,11] Different strategies have been developed to overcome tumor hypoxia through intelligent use of the tumor-abundant endogenous H 2 O 2 for O 2 self-supply, such as manganese-based, [12][13][14] platinum-based, [15][16][17] iron-based, [18][19][20] copper-based catalase-mimic inorganic materials, [21,22] alkyl borate-based organic materials, [11] and catalase biomaterials. [23][24][25] Among all approaches, employing catalase appears to be more suitable for relieving tumor hypoxia in vivo own to the excellent intrinsic biocompatibility, biodegradability, and extremely high catalytic ability of catalase.…”

Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery

“…To enhance the efficacy of oxygen-dependent PDT, platinum NPs (nano-Pt), acting as catalase (CAT)-like nanoenzymes, can generate oxygen through catalysis of elevated H 2 O 2 in cancer cells [62,63]. An example was designed by Liu et al; they adopted a reverse phase evaporation strategy to improve the aqueous drug loading capacity of nano-Pt in the liposome; then, the clinical hydrophobic photosensitizer verteporfin (VP) was loaded into the lipid bilayer to confer PDT activity.…”