Reactive oxygen species-activatable self-amplifying Watson-Crick base pairing-inspired supramolecular nanoprodrug for tumor-specific therapy

Xu, Xiaoyu; Zeng, Zishan; Ding, Xin; Shan, Ting; Liu, Qiuxing; Chen, Meixu; Chen, Jie; Xia, Meng; He, Yuanfeng; Huang, Zeqian; Huang, Yanjuan; Zhao, Chunshun

doi:10.1016/j.biomaterials.2021.121128

Cited by 26 publications

(30 citation statements)

References 48 publications

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“…tion (Figure 15A). 86 Anticancer drug GEM was covalently attached to cinnamaldehyde by forming ROS-cleavable thioacetal linkers. Considering the cytosine structure of GEM, a hyaluronic acid scaffold was further modified with guanine moieties to form Watson−Crick nucleobase pairs with cinnamaldehyde−gemcitabine conjugate molecules.…”

Section: Reduction-responsivementioning

confidence: 99%

Emerging Strategies in Stimuli-Responsive Prodrug Nanosystems for Cancer Therapy

Ding

Chen²,

Zeng

et al. 2022

ACS Nano

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Prodrugs are chemically modified drug molecules that are inactive before administration. After administration, they are converted in situ to parent drugs and induce the mechanism of action. The development of prodrugs has upgraded conventional drug treatments in terms of bioavailability, targeting, and reduced side effects. Especially in cancer therapy, the application of prodrugs has achieved substantial therapeutic effects. From serendipitous discovery in the early stage to functional design with pertinence nowadays, the importance of prodrugs in drug design is self-evident. At present, studying stimuli-responsive activation mechanisms, regulating the stimuli intensity in vivo, and designing nanoscale prodrug formulations are the major strategies to promote the development of prodrugs. In this review, we provide an outlook of recent cutting-edge studies on stimuli-responsive prodrug nanosystems from these three aspects. We also discuss prospects and challenges in the future development of such prodrugs.

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Section: Reduction-responsivementioning

confidence: 99%

Emerging Strategies in Stimuli-Responsive Prodrug Nanosystems for Cancer Therapy

Ding

Chen²,

Zeng

et al. 2022

ACS Nano

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“…-NH-, -OH/-C=O Figure 23 [95] Cytosine/Guanine (GEM/ACV) Figure 24 [96] medicine. Additionally, it is our intention to convey the broad prospects and excitement in using H-bonding design within drug delivery as these strategies can facilitate molecularly defined medicines, promoted therapeutic performance, and customized treatment options.…”

Section: Molecular-scale Organizationmentioning

confidence: 99%

“…C nucleobase, was fabricated to gain in responsiveness and selectivity (Figure 24). [96] A Figure 24. Preparation of CAG, HA-ACV conjugate, and pH/ROS dual-responsive H-bonded nanoprodrug HCAG a), in vivo selective anti-tumor mechanism of HCAG by ROS regeneration positive feedback process, along with the cascade-amplifying "snowballing" prodrug activation b).…”

Section: H-bond Driven Assembly Of Polymeric Carrier Encapsulating Sm...mentioning

confidence: 99%

“…With high stability, tumor selectivity, and pH/ROS‐responsiveness, HCAG nanoformulation demonstrates excellent in vivo antitumor efficacy with a minimal systemic toxicity ( Figure ). [ 96 ]…”

Section: Introductionmentioning

confidence: 99%

“…C nucleobase, was fabricated to gain in responsiveness and selectivity ( Figure ). [ 96 ] A ROS‐cleavable cinnamaldehyde (CA)‐based thioacetal linker CASOH bearing a ROS generator was designed to benefit from a self‐amplifying positive feedback loop of “ROS‐activated CA release along with CA‐induced ROS regeneration.” CASOH was functionalized with GEM to obtain a ROS‐activatable self‐immolative prodrug CAG, endowing selective activation in tumor cells and further achieving self‐boosting “snowballing” activation via ROS compensation, while staying inactive in normal cells. Thanks to Watson–Crick G .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hydrogen‐Bonds‐Mediated Nanomedicine: Design, Synthesis, and Applications

Chen

Lortie

et al. 2022

Macromol. Rapid Commun.

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Among the various challenges in medicine, diagnosis, complete cure, and healing of cancers remain difficult given the heterogeneity and complexity of such a disease. Differing from conventional platforms with often unsatisfactory theranostic capabilities, the contribution of supramolecular interactions, such as hydrogen-bonds (H-bonds), to cancer nanotheranostics opens new perspectives for the design of biomedical materials, exhibiting remarkable properties and easier processability. Thanks to their dynamic characteristics, a feature generally observed for noncovalent interactions, H-bonding (macro)molecules can be used as supramolecular motifs for yielding drug-and diagnostic carriers that possess attractive features, arising from the combination of assembled nanoplatforms and the responsiveness of H-bonds. Thus, H-bonded nanomedicine provides a rich toolbox that is useful to fulfill biomedical needs with unique advantages in early-stage diagnosis and therapy, demonstrating the promising potential in clinical translations and applications. Here the design and synthetic routes toward H-bonded nanomedicines, focus on the growing understanding of the structure-function relationship for efficient cancer treatment are summarized. A guidance for designing new H-bonded intelligent theranostic agents is proposed, to inspire more successful explorations of cancer nanotheranostics and finally to promote potential clinical translations.

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Reactive Oxygen Species‐Responsive Polymeric Prodrug Nanoparticles for Selective and Effective Treatment of Inflammatory Diseases

Zhang

Wang

et al. 2023

Adv Healthcare Materials

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It is challenging to manage inflammatory diseases using traditional anti‐inflammatory drugs due to their limited efficacy and systemic side effects, which are a result of their lack of selectivity, poor stability, and solubility. Herein, we report the development of a novel nanoparticle system, called ROS‐CA‐NPs, which is formed using polymer‐cinnamaldehyde (CA) conjugates and is responsive to reactive oxygen species (ROS). ROS‐CA‐NPs exhibit excellent drug stability, tissue selectivity, and controlled drug release upon oxidative stress activation. Using mouse models of chronic rheumatoid arthritis and acute ulcerative colitis, we demonstrate that the systemic administration of ROS‐CA‐NPs results in their accumulation at inflamed lesions and leads to greater therapeutic efficacy compared to traditional drugs. Furthermore, ROS‐CA‐NPs present excellent biocompatibility. Our findings suggest that ROS‐CA‐NPs have the potential to be developed as safe and effective nanotherapeutic agents for a broad range of inflammatory diseases.This article is protected by copyright. All rights reserved

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Reactive oxygen species-activatable self-amplifying Watson-Crick base pairing-inspired supramolecular nanoprodrug for tumor-specific therapy

Cited by 26 publications

References 48 publications

Emerging Strategies in Stimuli-Responsive Prodrug Nanosystems for Cancer Therapy

Emerging Strategies in Stimuli-Responsive Prodrug Nanosystems for Cancer Therapy

Hydrogen‐Bonds‐Mediated Nanomedicine: Design, Synthesis, and Applications

Reactive Oxygen Species‐Responsive Polymeric Prodrug Nanoparticles for Selective and Effective Treatment of Inflammatory Diseases

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