A Self-amplifying ROS-sensitive prodrug-based nanodecoy for circumventing immune resistance in chemotherapy-sensitized immunotherapy

Zhang, Jiulong; Sun, Xiaoyan; Xu, Mengdan; Zhao, Xiufeng; Yang, Chunrong; Li, Kexin; Zhao, Fan; Hu, Haiyang; Qiao, Mingxi; Chen, Fan; Zhao, Xin

doi:10.1016/j.actbio.2022.06.035

Cited by 15 publications

(11 citation statements)

References 46 publications

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“…[136,137] Furthermore, changes in surface groups can affect the affinity between NPs and APCs, an interaction pivotal for improving immunotherapy outcomes. [138,139]…”

Section: Surface Composition Of Npsmentioning

confidence: 99%

Nanoparticles Targeting Lymph Nodes for Cancer Immunotherapy: Strategies and Influencing Factors

Li,

Zhong,

Cao

et al. 2024

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Immunotherapy has emerged as a potent strategy in cancer treatment, with many approved drugs and modalities in the development stages. Despite its promise, immunotherapy is not without its limitations, including side effects and suboptimal efficacy. Using nanoparticles (NPs) as delivery vehicles to target immunotherapy to lymph nodes (LNs) can improve the efficacy of immunotherapy drugs and reduce side effects in patients. In this context, this paper reviews the development of LN‐targeted immunotherapeutic NP strategies, the mechanisms of NP transport during LN targeting, and their related biosafety risks. NP targeting of LNs involves either passive targeting, influenced by NP physical properties, or active targeting, facilitated by affinity ligands on NP surfaces, while alternative methods, such as intranodal injection and high endothelial venule (HEV) targeting, have uncertain clinical applicability and require further research and validation. LN targeting of NPs for immunotherapy can reduce side effects and increase biocompatibility, but risks such as toxicity, organ accumulation, and oxidative stress remain, although strategies such as biodegradable biomacromolecules, polyethylene glycol (PEG) coating, and impurity addition can mitigate these risks. Additionally, this work concludes with a future‐oriented discussion, offering critical insights into the field.

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“…[136,137] Furthermore, changes in surface groups can affect the affinity between NPs and APCs, an interaction pivotal for improving immunotherapy outcomes. [138,139]…”

Section: Surface Composition Of Npsmentioning

confidence: 99%

Nanoparticles Targeting Lymph Nodes for Cancer Immunotherapy: Strategies and Influencing Factors

Li,

Zhong,

Cao

et al. 2024

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“…This could be due to the inefficient and uncontrolled release of drugs from the non-responsive particles. 6,22,24 Therefore, the development of smart nanocarriers is highly desirable to achieve effective delivery of these prodrugs. 25 In particular, the use of self-assembly of block copolymers has emerged as a highly regarded nanocarrier system, attracting significant attention.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Similar results were observed in most other formulations loaded with dimeric prodrugs. This could be due to the inefficient and uncontrolled release of drugs from the non-responsive particles. ,, Therefore, the development of smart nanocarriers is highly desirable to achieve effective delivery of these prodrugs …”

Section: Introductionmentioning

confidence: 99%

pH-Responsive Micellar Nanoparticles for the Delivery of a Self-Amplifying ROS-Activatable Prodrug

Kannaujiya,

Qiao,

Sheikh

et al. 2024

Biomacromolecules

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The objective of this study is to enhance the therapeutic efficacy of the anticancer drug, camptothecin (CPT) via a nanoparticle (NP) formulation using a novel amphiphilic biopolymer. We have designed a dimeric prodrug of CPT with the ability to self-amplify and respond to reactive oxygen species (ROS). For this, we incorporated the intracellular ROS generator cinnamaldehyde into a ROS-cleavable thioacetal (TA) linker to obtain the dimeric prodrug of CPT (DCPT(TA)). For its efficient NP delivery, a pH-responsive block copolymer of acetalated dextran and poly(2-ethyl-2-oxazoline) (AcDex-b-PEOz) was synthesized. The amphiphilic feature of the block copolymer enables its self-assembly into micellar NPs and results in high prodrug loading capacity and a rapid release of the prodrug under acidic conditions. Upon cellular uptake by HeLa cells, DCPT(TA)-loaded micellar NPs induce intracellular ROS generation, resulting in accelerated prodrug activation and enhanced cytotoxicity. These results indicate that this system holds significant potential as an effective prodrug delivery strategy in anticancer treatment.

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“…Immunotherapy has emerged as a powerful therapeutic strategy for cancer treatment, which could kill tumor cells through host immune system with long protection effects. However, the lack of immunogenicity in tumor leads to insufficient immune responses [1][2][3]. Immunosuppressive tumor microenvironment further promotes tumor cells escape from antitumor immunity and conventional therapeutical strategies such like chemotherapy [4].…”

Section: Introductionmentioning

confidence: 99%

“…1 H NMR of 1-MT(Boc) acrylate in CDCl 3 showed δ = 1.26 (-Boc), 4.13 (-CH-), 5.8 and 5.3 (CH 2 = CH-) and 7.43 (phenyl), indicating the protection of -NH 2 and conjugation with the monomer. Subsequentially, phenyl-ox-acrylate monomer with peroxalate ester bond was synthesized and the representative 1 H NMR result was displayed in Additional file 1: Fig.S2.…”

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confidence: 98%

Efficient tumor synergistic chemoimmunotherapy by self-augmented ROS-responsive immunomodulatory polymeric nanodrug

et al. 2023

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Immunotherapy has emerged as a promising therapeutic strategy for cancer therapy. However, the therapeutic efficacy has been distracted due to poor immunogenicity and immunosuppressive tumor microenvironment. In this study, a self-augmented reactive oxygen species (ROS) responsive nanocarrier with immunogenic inducer paclitaxel (PTX) and indoleamine 2,3-dixoygenase 1 (IDO1) blocker 1-methyl-d, L-tryptophan (1-MT) co-entrapment was developed for tumor rejection. The carrier was composed of poly (ethylene glycol) (PEG) as hydrophilic segments, enzyme cleavable 1-MT ester and ROS-sensitive peroxalate conjugation as hydrophobic blocks. The copolymer could self-assemble into prodrug-based nanoparticles with PTX, realizing a positive feedback loop of ROS-accelerated PTX release and PTX induced ROS generation. Our nanoparticles presented efficient immunogenic cell death (ICD) which provoked antitumor immune responses with high effector T cells infiltration. Meanwhile immunosuppressive tumor microenvironment was simultaneously modulated with reduced regulatory T cells (Tregs) and M2-tumor associated macrophages (M2-TAMs) infiltration mediated by IDO inhibition. The combination of PTX and 1-MT achieved significant primary tumor regression and reduction of lung metastasis in 4T1 tumor bearing mice. Therefore, the above results demonstrated co-delivery of immunogenic inducer and IDO inhibitor using the ROS amplifying nanoplatform with potent potential for tumor chemoimmunotherapy.

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A Self-amplifying ROS-sensitive prodrug-based nanodecoy for circumventing immune resistance in chemotherapy-sensitized immunotherapy

Cited by 15 publications

References 46 publications

Nanoparticles Targeting Lymph Nodes for Cancer Immunotherapy: Strategies and Influencing Factors

Nanoparticles Targeting Lymph Nodes for Cancer Immunotherapy: Strategies and Influencing Factors

pH-Responsive Micellar Nanoparticles for the Delivery of a Self-Amplifying ROS-Activatable Prodrug

Efficient tumor synergistic chemoimmunotherapy by self-augmented ROS-responsive immunomodulatory polymeric nanodrug

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