Dataset Information

Reactive oxygen species-responsive and Raman-traceable hydrogel combining photodynamic and immune therapy for postsurgical cancer treatment.

ABSTRACT: Combining immune checkpoint blockade (ICB) therapy with photodynamic therapy (PDT) holds great potential in treating immunologically "cold" tumors, but photo-generated reactive oxygen species (ROS) can inevitably damage co-administered ICB antibodies, hence hampering the therapeutic outcome. Here we create a ROS-responsive hydrogel to realize the sustained co-delivery of photosensitizers and ICB antibodies. During PDT, the hydrogel skeleton poly(deca-4,6-diynedioic acid) (PDDA) protects ICB antibodies by scavenging the harmful ROS, and at the same time, triggers the gradual degradation of the hydrogel to release the drugs in a controlled manner. More interestingly, we can visualize the ROS-responsive hydrogel degradation by Raman imaging, given the ultrastrong and degradation-correlative Raman signal of PDDA in the cellular silent window. A single administration of the hydrogel not only completely inhibits the long-term postoperative recurrence and metastasis of 4T1-tumor-bearing mice, but also effectively restrains the growth of re-challenged tumors. The PDDA-based ROS-responsive hydrogel herein paves a promising way for the durable synergy of PDT and ICB therapy.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC9356008 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Reactive oxygen species-responsive and Raman-traceable hydrogel combining photodynamic and immune therapy for postsurgical cancer treatment.

Zhang Yiyi Y Tian Sidan S Huang Liping L Li Yanan Y Lu Yuan Y Li Hongyu H Chen Guiping G Meng Fanling F Liu Gang L GL Yang Xiangliang X Tu Jiasheng J Sun Chunmeng C Luo Liang L

Nature communications 20220805 1

Combining immune checkpoint blockade (ICB) therapy with photodynamic therapy (PDT) holds great potential in treating immunologically "cold" tumors, but photo-generated reactive oxygen species (ROS) can inevitably damage co-administered ICB antibodies, hence hampering the therapeutic outcome. Here we create a ROS-responsive hydrogel to realize the sustained co-delivery of photosensitizers and ICB antibodies. During PDT, the hydrogel skeleton poly(deca-4,6-diynedioic acid) (PDDA) protects ICB anti ...[more]

PMID: 35931666

Similar Datasets

Project description:Radiofrequency catheter ablation (RFCA) is the preferred technique for the treatment of atrial fibrillation, but the recovery of electrical conduction after ablation seriously endangers the health of patients. This study aimed to develop reactive oxygen species (ROS) responsive double-locked liposome collaborative photodynamic therapy (PDT) to target the ablation area and reduce the recovery of electrical conduction after ablation. The successful synthesis of β-cyclodextrin modified with phenylboronic acid pinacol ester (OCD) was confirmed by 1H NMR and FT-IR. Furthermore, the successful synthesis of octadecylamine-modified indocyanine green (ICG-ODA) was confirmed by 1H NMR and mass spectrometry. The ICG-ODA was encapsulated in liposomes to generate a double-locked hybrid liposome (ICG-ODA@rNP), which was subsequently characterized. Several properties of ICG-ODA@rNP were evaluated, including the drug release, targeting ability and ability to inhibit electrical conduction recurrence. Moreover, a model was constructed for the blockage of electrical conduction after RFCA in rabbits to further evaluate ICG-ODA@rNP. The preliminary safety evaluation of ICG-ODA@rNP was also performed. The ICG-ODA@rNP with a uniform particle size showed excellent storage stability. The nanoparticle can sensitively release drugs under ROS environment, and exhibits excellent photothermal effects. Furthermore, ICG-ODA@rNP can circulate for a long time in vivo and accumulate significantly in the ablation area. In a pacing test with a left atrial appendage (LAA), these nanoparticles, combined with PDT, reduced the ratio of electrical conduction recovery, which was confirmed by a hematoxylin and eosin (H&E) test. Further molecular analysis revealed that ICG-ODA@rNP could increase RFCA-induced apoptosis and ROS levels. Specifically, ICG-ODA@rNP significantly increased the expression of Bax and cleaved caspase-3, and decreased the expression of Bcl-2. In addition, the excellent biosafety of the double-locked nanoparticle was verified. This study provides evidence that ICG-ODA@rNP, with the double lock characteristic and biosafety, which exhibits a targeting effect on RFCA-induced cardiac injury areas, which further reduce electrical conduction recovery in RFCA areas by collaborativing PDT.

Project description:Lumbar disc degeneration is a common cause of chronic low back pain and an important contributor to various degenerative lumbar spinal disorders. However, currently there is currently no effective therapeutic strategy for treating disc degeneration. The pro-inflammatory cytokine interleukin-1β (IL-1β) mediates disc degeneration by inducing apoptotic death of nucleus pulposus (NP) cells and degradation of the NP extracellular matrix. Here, we confirmed that extracellular secretion of IL-1β via secretory autophagy contributes to disc degeneration, and demonstrate that a thermosensitive reactive oxygen species (ROS)-responsive hydrogel loaded with a synthetic growth hormone-releasing hormone analog (MR409) can protect against needle puncture-induced disc degeneration in rats. Methods: The expression levels of proteins related to secretory autophagy such as tripartite motif-containing 16 (TRIM16) and microtubule-associated protein light chain 3B (LC3B) were examined in human and rat disc tissues by histology and immunofluorescence. The effects of TRIM16 expression level on IL-1β secretion were examined in THP-1 cells transfected with TRIM16 plasmid or siRNA using ELISA, immunofluorescence, and immunoblotting. The in vitro effects of MR409 on IL-1β were examined in THP-1 cells and primary rat NP cells using ELISA, immunofluorescence, immunoblotting, and qRT-PCR. Further, MR409 was subcutaneously administered to aged mice to test its efficacy against disc degeneration using immunofluorescence, X-ray, micro-CT, and histology. To achieve controllable MR409 release for intradiscal use, MR409 was encapsulated in an injectable ROS-responsive thermosensitive hydrogel. Viscosity, rheological properties, release profile, and biocompatibility were evaluated. Thereafter, therapeutic efficacy was assessed in a needle puncture-induced rat model of disc degeneration at 8 and 12 weeks post-operation using X-ray, magnetic resonance (MR) imaging, histological analysis, and immunofluorescence. Results: Secretory autophagy-related proteins TRIM16 and LC3B were robustly upregulated in degenerated discs of both human and rat. Moreover, while upregulation of TRIM16 facilitated, and knockdown of TRIM16 suppressed, secretory autophagy-mediated IL-1β secretion from THP-1 cells under oxidative stress, MR409 inhibited ROS-induced secretory autophagy and IL-1β secretion by THP-1 cells as well as IL-1β-induced pro-inflammatory and pro-catabolic effects in rat NP cells. Daily subcutaneous injection of MR409 inhibited secretory autophagy and ameliorated age-related disc degeneration in mice. The newly developed ROS-responsive MR409-encapsulated hydrogel provided a reliable delivery system for controlled MR409 release, and intradiscal application effectively suppressed secretory autophagy and needle puncture-induced disc degeneration in rats. Conclusion: Secretory autophagy and associated IL-1β secretion contribute to the pathogenesis of disc degeneration, and MR409 can effectively inhibit this pathway. The ROS-responsive thermosensitive hydrogel encapsulated with MR409 is a potentially efficacious treatment for disc degeneration.

Dataset Information

Reactive oxygen species-responsive and Raman-traceable hydrogel combining photodynamic and immune therapy for postsurgical cancer treatment.

Publications

Reactive oxygen species-responsive and Raman-traceable hydrogel combining photodynamic and immune therapy for postsurgical cancer treatment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets