Biomimetic Nanoparticle with Glutathione Depletion and Amplified ROS Generation Capabilities for Synergistic Chemo-Sonodynamic Therapy in Squamous Cell Carcinomas

Abstract

Nanomedicines for combining chemotherapy and sonodynamic therapy (SDT) have enormous potential in squamous cell carcinoma treatment. However, the therapeutic efficacy of noninvasive SDT is severely limited because the generation of reactive oxygen species (ROS) by sonosensitizers is highly dependent on the levels of intracellular excess glutathione (GSH) in the tumor cells. To overcome this barrier, a red blood cell (RBC) membrane-camouflaged nanomedicine consisting of GSH-sensitive polyphosphoester (SS-PPE) and ROS-sensitive polyphosphoester (S-PPE) was designed for the simultaneous delivery of the sonosensitizer hematoporphyrin (HMME) and chemotherapeutic agent docetaxel (DTXL) for effectively enhanced antitumor efficacy. In vitro and in vivo studies demonstrated that HMME-driven ROS generation under ultrasound (US) inhibited SCC7 cell proliferation and accelerated DTXL release to further kill tumor cells via the hydrophobic–hydrophilic transition of the nanoparticle core. Meanwhile, the disulfide bond of SS-PPE effectively consumes GSH to prevent ROS consumption. This biomimetic nanomedicine provides GSH depletion and amplified ROS generation capabilities to achieve a novel synergistic chemo-SDT strategy for squamous cell carcinomas.

Cell Membrane-Camouflaged Nanoparticles Mediated Nucleic Acids Delivery

“…Nanoparticles can be camouflaged with different cell membranes from erythrocytes, [57][58][59][60] platelets, [61][62][63] macrophages, [64][65][66][67] cancer cells, [68][69][70][71][72][73][74] stem cells, [75][76][77][78] dendritic cells, [79][80][81] neutrophil, [82][83][84] exosomes, [85][86][87] or other membranes depend on desired applications (Figure 4). Blood cells likes erythrocytes and platelets could reduce endothelial reticular system clearance and prolong half-time.…”

Self-Assembled R848/Chlorin e6 Nanoparticles for Combinatorial Immunotherapy of Head and Neck Squamous Cell Carcinoma

“…Activating Toll-like receptors (TLRs) has been demonstrated to reprogram the immunosuppressive tumor microenvironment (TME) and boost antitumor response. − Following stimulation by TLR agonists, a cascade of signaling pathways are primed, triggering the activation of antigen-presenting cells and the infiltration of T cells . The TLR7/8 agonist resiquimod (R848) has been extensively studied for its ability to regulate both innate and adaptive immune responses. , However, the limited pharmacokinetic properties and the risk of off-target systemic toxicity associated with R848 hinder its biomedical applications .…”

A copper-loaded self-assembled nanoparticle for disturbing the tumor redox balance and triple anti-tumor therapy

“…23 With the development of nanotechnology, the integration of GSH-depletion agents with other therapies (SDT, CDT or PDT) to prepare synergistic nanomedicines has been widely developed recently. [24][25][26][27] Cheng et al constructed iron-rich mesoporous dopamine (MPDA@Fe) nanovehicles, which facilitate the dual depletion of GSH by both Fe and MPDA. This synergistic action enhances lipid peroxidation and enables the induction of ferroptosis.…”