Cascade-amplifying synergistic effects of chemo-photodynamic therapy using ROS-responsive polymeric nanocarriers

Abstract

The simple integration of chemotherapeutic drugs and photosensitizers (PSs) into the same nanocarriers only achieves a combination of chemo-photodynamic therapy but may not confer synergistic effects. The boosted intracellular release of chemotherapeutic drugs during the photodynamic therapy (PDT) process is necessary to achieve a cascade of amplified synergistic therapeutic effects of chemo-photodynamic therapy.Methods: In this study, we explored an innovative hyperbranched polyphosphate (RHPPE) containing a singlet oxygen (SO)-labile crosslinker to boost drug release during the PDT process. The photosensitizer chlorin e6 (Ce6) and doxorubicin (DOX) were simultaneously loaded into RHPPE nanoparticles (denoted as SOHNPCe6/DOX). The therapeutic efficacy of SOHNPCe6/DOX against drug-resistant cancer was evaluated in vitro and in vivo.Results: Under 660-nm light irradiation, SOHNPCe6/DOX can produce SO, which not only induces PDT against cancer but also cleaves the thioketal linkers to destroy the nanoparticles. Subsequently, boosted DOX release can be achieved, activating a chemotherapy cascade to synergistically destroy the remaining tumor cells after the initial round of PDT. Furthermore, SOHNPCe6/DOX also efficiently detected the tumor area by photoacoustic/magnetic resonance bimodal imaging. Under the guidance of bimodal imaging, the laser beam was precisely focused on the tumor areas, and subsequently, SOHNPCe6/DOX realized a cascade of amplified synergistic chemo-photodynamic therapeutic effects. High antitumor efficacy was achieved even in a drug-resistant tumor model.Conclusion: The designed SOHNPCe6/DOX with great biocompatibility is promising for use as a co-delivery carrier for combined chemo-photodynamic therapy, providing an alternative avenue to achieve a cascade of amplified synergistic effects of chemo-photodynamic therapy for cancer treatment.

ROS‐Responsive Blended Nanoparticles: Cascade‐Amplifying Synergistic Effects of Sonochemotherapy with On‐demand Boosted Drug Release During SDT Process

“…US exposure also significantly increased the fluorescence of IR780 from the IR780/PTL‐NPs in an intensity‐dependent manner compared to the nonirradiated nanoparticles (Figure D), indicating that IR780 was released from IR780/PTL‐NPs. This is consistent with a previous report showing that fluorescent molecules loaded on nanoparticles undergo quenching occurs due to local accumulation . Transmission electron microscopy (TEM) (Figure E,F) and DLS (Figure S3, Supporting Information) showed that US irradiation had a negligible impact on the morphology of PTL‐NPs, but resulted in the disintegration of IR780/PTL‐NPs, likely due to the ROS‐triggered cleavage of the TL bonds as described.…”

Smart Nanotheranostics Responsive to Pathological Stimuli

“…It is worth mentioning that all ROS-responsive mechanisms eventually depend on a biological trigger because their working mechanism depends on the oxygen content in the tissue, and they are ineffective in hypoxic regions (Chen et al, 2015). In some cases, the ROS generation is catalyzed directly by the nanoparticles, that due to the properties of their synthesis material, can activate other features of the carriers like payload release (Sun et al, 2018).…”

“…For this reason, the carriers needed to generate ROS as well as being sensitive to these chemical species. To this goal, Sun et al (2018) developed nanoparticles of pegylated polyphosphate crosslinked with a thioketal linker via (A2 + B3) type polycondensation. The carriers were loaded with the photosensitizer Ce6 and DOX.…”

Physical‐, chemical‐, and biological‐responsive nanomedicine for cancer therapy

“…Kim, Jo, et al (2018). Copyright 2018 Wiley) PEGylated hyperbranched polyphosphate (abbreviated as RHPPE) with a thioketal cross-linker, which can induce drug burst release during photodynamic therapy (PDT; Sun et al, 2018). The RHPPE loaded with Ce6 and DOX, simultaneously.…”