All-in-One Theranostic Nanoplatform Based on Hollow MoS_x for Photothermally-maneuvered Oxygen Self-enriched Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) kills cancer cells by converting tumor-dissolved oxygen into reactive singlet oxygen (1O2) using a photosensitizer under laser irradiation. However, pre-existing hypoxia in tumors and oxygen consumption during PDT can result in an inadequate oxygen supply, which in turn hampers PDT efficacy. Herein, an O2 self-sufficient nanotheranostic platform based on hollow MoSx nanoparticles (HMoSx) with oxygen-saturated perfluorohexane (O2@PFH) and surface-modified human serum albumin (HSA)/chloride aluminium phthalocyanine (AlPc) (O2@PFH@HMoSx-HSA/AlPc), has been designed for the imaging and oxygen self-enriched photodynamic therapy (Oxy-PDT) of cancer.Methods: The in vitro anti-cancer activity and intracellular 1O2 generation performance of the nanoparticles were examined using 4T1 cells. We also evaluated the multimodal imaging capabilities and anti-tumor efficiency of the prepared nanoparticles in vivo using a 4T1 tumor-bearing nude mouse model.Results: This nanoplatform could achieve the distinct in vivo fluorescence (FL)/photoacoustic (PA)/X-ray computed tomography (CT) triple-model imaging-guided photothermally-maneuvered Oxy-PDT. Interestingly, the fluorescence and Oxy-PDT properties of O2@PFH@HMoSx-HSA/AlPc were considerably quenched; however, photothermal activation by 670 nm laser irradiation induced a significant increase in temperature, which empowered the Oxy-PDT effect of the nanoparticles. In this study, O2@PFH@HMoSx-HSA/AlPc demonstrated a great potential to image and treat tumors both in vitro and in vivo, showing complete tumor-inhibition over 16 days after treatment in the 4T1 tumor model.Conclusion: O2@PFH@HMoSx-HSA/AlPc is promising to be used as novel multifunctional theranostic nanoagent for triple-modal imaging as well as single wavelength NIR laser triggered PTT/Oxy-PDT synergistic therapy.

A Porous Au@Rh Bimetallic Core–Shell Nanostructure as an H2O2‐Driven Oxygenerator to Alleviate Tumor Hypoxia for Simultaneous Bimodal Imaging and Enhanced Photodynamic Therapy

“…Various nanomaterial‐enabled systems have been explored to alleviate tumor hypoxia. [ 8 ] So far, three major strategies have been taken, including: 1) the use of oxygen‐carrying nanomaterials, based on perfluorocarbon or hemoglobin, for direct delivery of oxygen into tumor sites, [ 9 ] 2) in situ generation of oxygen upon decomposition of chemicals (such as C 3 N 4 and CaO 2 ) carried by nanomaterials to the tumor site, [ 10 ] and 3) in situ conversion of endogenous hydrogen peroxide (H 2 O 2 ) into oxygen using catalytic nanoparticles. [ 11 ] As a result of abnormal pathophysiologic processes in tumors (e.g., overexpression of NADPH oxidase (NOX) enzymes), elevated H 2 O 2 at a typical generation rate of 5 nmol per 10 5 cells h −1 is consistently observed in the tumor microenvironment.…”

Theranostic nanocomposite from upconversion luminescent nanoparticles and black phosphorus nanosheets

“…1 Research in the eld of nanotechnology recently introduced some promising theranostic nanomedicines that combine therapeutic and imaging components into one single nanoplatform. [2][3][4][5][6][7][8][9] Theranostic nanomedicines provide real-time image guided disease diagnosis and assessment of treatment efficacy. Compared to traditional one-modal therapy which has many disadvantages such as system and organ toxicity, poor bioavailability and impaired target specicity, multi-modal therapy showed promising effects in cancer treatment because of its high efficiency and low risk of cancer recurrence.…”

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

“…This hypoxia‐induced decline of the antitumor effect was obviously eased when an abundant of O 2 was provided by the catalysis of ICG‐PtMGs@HGd under the H 2 O 2 ‐containing environment (Figure 3c). The apoptosis and necrosis assay under hypoxic condition was further performed by flow cytometry with Annexin V‐FITC/PI kit to investigate the level and the mechanism of cell death [ 24a ] (Figure 3d). A cell survival of 75.8% was detected when the 4T1 cells were treated with free ICG, suggesting slight apoptosis.…”

“…[ 23 ] Meanwhile, the coating of endogenous HSA that is approved by the U.S. Food and Drug Administration (FDA) for intravenous administration increases the biocompatibility, stability, and tumor targeting effect (passive or active) of the nanoplatforms. [ 24 ] Finally, indocyanine green (ICG), a commercially NIR organic dye that has been approved by FDA is loaded into the nanoplatform, endowing the nanocarriers synergistic PDT/PTT effect as well as fluorescence (FL)/multispectral optoacoustic tomography (MSOT) imaging. [ 25 ]…”