A reactive oxygen species–responsive prodrug micelle with efficient cellular uptake and excellent bioavailability

Xu, Long; Yang, Yidi; Zhao, Mingying; Gao, Wenxia; Zhang, Hai; Li, Sai; He, Bin; Pu, Yuji

doi:10.1039/c7tb02479g

Cited by 61 publications

(39 citation statements)

References 48 publications

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“…The DOX-loaded mPEG-TK-PCL micelles demonstrated enhanced anticancer activity due to the rapid cleavage of the thioketal linker in the presence of increased ROS levels in cancer cells, thereby accelerating drug release and augmenting cancer cell inhibition. Xu et al [ 1 ] have developed a ROS-responsive prodrug through the thioketal linkage of PEG and DOX (Fig. 5 ).…”

Section: Targeting Of Common Attributes Of Tmementioning

confidence: 99%

“…5 Schematic illustration of ( a ) synthesis of ROS–responsive prodrug mPEG-TK- DOX and ( b ) illustration of ROS–responsive prodrug micelle and DOX-loaded prodrug micelle for drug delivery. Reproduced with permission [ 1 ] Copyright © 2018, Royal Society of Chemistry …”

Section: Targeting Of Common Attributes Of Tmementioning

confidence: 99%

“…Chemotherapy is one of the clinically practiced treatments for cancer. Over the past few decades, efforts have been made to deliver of small-molecule anticancer drugs to solid tumor however, therapeutic efficacy of these drugs are limited by many factors including low bio-availability, poor water solubility and poor targeting to tumor region [ 1 ]. The introduction of nanotechnology for cancer treatment has prompted the development of various nanomedicines, which are more effective and safer than conventional cancer therapies [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

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Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications

2018

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BackgroundCancer is one of the deadliest threats to human health. Abnormal physiochemical conditions and dysregulated biosynthetic intermediates in the tumor microenvironment (TME) play a significant role in modulating cancer cells to evade or defend conventional anti-cancer therapy such as surgery, chemotherapy and radiotherapy. One of the most important challenges in the development of anti-tumor therapy is the successful delivery of therapeutic and imaging agents specifically to solid tumors.Main bodyThe recent progresses in development of TME responsive nanoparticles offers promising strategies for combating cancer by making use of the common attributes of tumor such as acidic and hypoxic microenvironments. In this review, we discussed the prominent strategies utilized in the development of tumor microenvironment-responsive nanoparticles and mode of release of therapeutic cargo.ConclusionTumor microenvironment-responsive nanoparticles offers a universal approach for anti-cancer therapy.

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Section: Targeting Of Common Attributes Of Tmementioning

confidence: 99%

Section: Targeting Of Common Attributes Of Tmementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications

2018

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“…The system was triggered by light irradiation (producing ROS) for combined chemo‐ and photodynamic therapy. Similarly, Pu and co‐workers reported a thioketal‐linked nanoparticle with mPEG polymer with an efficient level of cellular uptake and good bioavailability. Another self‐assembled nanoparticle based on thioketal‐linkages, in which the photosensitizer hematoporphyrin (HP) was encapsulated, has been developed by Wang and co‐workers .…”

Section: Ros‐activated Drug Delivery and Small‐molecular Prodrug Systemsmentioning

confidence: 89%

Sensors, Imaging Agents, and Theranostics to Help Understand and Treat Reactive Oxygen Species Related Diseases

et al. 2019

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Reactive oxygen species (ROS) consist of a diverse range of oxidative small molecular ions and free radicals that are produced throughout the body during certain biological processes. Due to their high reactivity, these molecules result in the damage of tissues and cells. Therefore, ROS have been implicated in an array of diseases including cancer, inflammation, and neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Owing to the simplicity, sensitivity, and selectivity of fluorescence‐based strategies, many small‐molecular sensors or imaging agents have been developed to sense and visualize ROS both in vitro and in vivo. Likewise, activatable drug delivery and prodrug systems that can be triggered by ROS for disease theranostics (diagnostic and therapeutic combined) have been developed. Herein, recently developed fluorescence‐based sensing and imaging agents for the detection of ROS both intracellularly and in vivo are summarized. In addition, drug delivery, which require activation by ROS to achieve disease theranostics is also discussed.

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“…Meanwhile, we investigated the drug release behaviors of Nile Red‐loaded PHBDT‐ g ‐C 8 microspheres in the presence of different H 2 O 2 concentrations (0.1 and 1 m m ). H 2 O 2 is abundant in inflamed and tumor tissues (about 0.1 m m ), and it has been widely investigated as an exogenous trigger for ROS‐responsive release of therapeutic payload in the lesion sites . The stability of Nile Red in H 2 O 2 endued it a good hydrophobic model drug to study the drug release profile in simulated ROS environment.…”

Section: Methodsmentioning

confidence: 99%

Polymer Structure‐Guided Self‐Assisted Preparation of Poly(ester‐thioether)‐Based Hollow Porous Microspheres and Hierarchically Interconnected Microcages for Drug Release

Cheng

et al. 2019

Macromolecular Bioscience

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/mabi.201900171. Porous MicrospheresPorous polymer microspheres (PPMs) have been widely applied in various biomedical fields. Herein, the self-assisted preparation of poly(esterthioether)-based porous microspheres and hierarchical microcages, whose pore sizes can be controlled by varying the polymer structures, is reported. Poly(ester-thioether)s with alkyl side chains (carbon atom numbers were 2, 4, and 8) can generate hollow porous microspheres; the longer alkyl chain length, the larger pore size of microspheres. The allyl-modified poly(esterthioether) (PHBDT-g-C 3 ) can form highly open, hierarchically interconnected microcages. A formation mechanism of these PPMs is proposed; the hydrophobic side chains-mediated stabilization of oil droplets dictate the droplet aggregation and following solvent evaporation, which is the key to the formation of PPMs. The hierarchically interconnected microcages of PHBDT-g-C 3 are due to the partially crosslinking of polymers. Pore sizes of PPMs can be further tuned by a simple mixing strategy of poly(esterthioether)s with different pore-forming abilities. The potential application of these PPMs as H 2 O 2 -responsive vehicles for delivery of hydrophobic (Nile Red) and hydrophilic (doxorubicin hydrochloride) cargos is also investigated. The microspheres with larger pore sizes show faster in vitro drug release. The poly(ester-thioether)-based polymer microspheres can open a new avenue for the design of PPMs and provide a H 2 O 2 -responsive drug delivery platform.

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A reactive oxygen species–responsive prodrug micelle with efficient cellular uptake and excellent bioavailability

Abstract: Stimuli-responsive polymeric drug delivery systems are of great interest in anticancer research. Here, a reactive oxygen species (ROS)–responsive prodrug was prepared by thioketal linkage of poly(ethylene glycol) (PEG) and the anticancer drug doxorubicin (DOX).

Cited by 61 publications

References 48 publications

Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications

Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications

Sensors, Imaging Agents, and Theranostics to Help Understand and Treat Reactive Oxygen Species Related Diseases

Polymer Structure‐Guided Self‐Assisted Preparation of Poly(ester‐thioether)‐Based Hollow Porous Microspheres and Hierarchically Interconnected Microcages for Drug Release

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