Targeting tumor hypoxia with stimulus-responsive nanocarriers in overcoming drug resistance and monitoring anticancer efficacy

Xie, Zhiqi; Guo, Wang-Wei; Guo, Ningning; Huang-Fu, Ming-Yi; Liu, Huina; Lin, Meng-Ting; Xu, Wenhong; Chen, Jiejian; Wang, Tiantian; Wei, Qichun; Han, Min; J, Gao

doi:10.1016/j.actbio.2018.03.013

Cited by 46 publications

(23 citation statements)

References 45 publications

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“…The exposed positive charge on the particles further facilitated the enhanced cellular uptake of PEI/siRNA nanoparticles. Xie et al [ 45 ] reported the development of hypoxia responsive nanoparticles for the codelivery of siRNA and DOX. In this study, polyamidoamine (PAMAM) dendrimer was conjugated to PEG using AZO, which is a hypoxia-sensitive linker to form PAMAM-AZO-PEG (PAP).…”

Section: Targeting Of Common Attributes Of Tmementioning

confidence: 99%

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%

Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications

2018

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“…Due to the significant role of hypoxia in cancer multidrug resistance, angiogenesis, invasion, and metastasis (Wilson and Hay, 2011), persistent efforts have been put forward to develop a targeting hypoxia region or hypoxia responsive nanoparticles. Xie et al fabricated a hypoxiaresponsive size-shrinkable nanoparticle for co-delivery of DOX, siRNA, and a ROS probe to increase penetration into the tumor (Xie et al, 2018). The size-switchable nanovehicle was designed by conjugation of the polyamidoamine (PAMAM) dendrimer, which was a globular-shaped macromolecule with an ultrasmall size to PEG 2000 via a hypoxia-sensitive linker azobenzene (AZO) (Figure 1).…”

Section: Hypoxia-responsive Size-shrinkable Nanodrugsmentioning

confidence: 99%

Tumor-Microenvironment- Responsive Size-Shrinkable Drug-Delivery Nanosystems for Deepened Penetration Into Tumors

Cheng

et al. 2020

Front. Mol. Biosci.

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Over the years, the manipulation and clinical application of drug-delivery nanosystems for cancer diseases have attracted a rapid growth of academic research interests, and some nanodrugs have been approved for clinic application. Although encouraging achievements have been made, the potency of nanomedicines in cancer treatment is far from satisfaction, and one significant reason is the inefficient penetration of nanoparticles into solid tumors. Particle size is one of the most significant features that influence diffusion ability of the drug-delivery system in tumors. Size-shrinkable drug-delivery nanosystems possess a size-switchable property that can achieve passive targeting via the enhanced permeability and retention (EPR) effect and transform into ultrasmall particles in tumors for deep penetration into tumors. The tumor microenvironment is characterized by acidic pH, hypoxia, upregulated levels of enzymes, and a redox environment. In this review, we summarize and analyze the current research progresses and challenges in tumor microenvironment responsive size-shrinkable drug-delivery nanosystems. We further expect to present some meaningful proposals and enlightenments on promoting deep penetration into tumors of nanoparticles.

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“…Thus, an ideal nanoparticle should be relatively large in the blood circulation to prevent the renal filtration to achieve tumor-specific delivery through the enhanced permeability and retention effect and transform into small particles to penetrate into tumors once inside the tumor microenvironment. Xie et al89 developed the first hypoxia-activated nanoparticles capable of decreased size for the co-delivery of doxorubicin and siRNA. Polyamidoamine (PAMAM) dendrimer was conjugated to PEG-2000 using the AZO hypoxia-sensitive to form PAMAM-AZO-PEG (collectively abbreviated PAP).…”

Section: Hypoxia-active Nanoparticles For Chemotherapymentioning

confidence: 99%

<p>Hypoxia-active nanoparticles used in tumor theranostic</p>

Wang¹,

Shang²,

Niu³

et al. 2019

IJN

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Hypoxia is a hallmark of malignant tumors and often correlates with increasing tumor aggressiveness and poor treatment outcomes. Therefore, early diagnosis and effective killing of hypoxic tumor cells are crucial for successful tumor control. There has been a surge of interdisciplinary research aimed at developing functional molecules and nanomaterials that can be used to noninvasively image and efficiently treat hypoxic tumors. These mainly include hypoxia-active nanoparticles, anti-hypoxia agents, and agents that target biomarkers of tumor hypoxia. Hypoxia-active nanoparticles have been intensively investigated and have demonstrated advanced effects on targeting tumor hypoxia. In this review, we present an overview of the reports published to date on hypoxia-activated prodrugs and their nanoparticle forms used in tumor-targeted therapy. Hypoxia-responsive nanoparticles are inactive during blood circulation and normal physiological conditions but are activated by hypoxia once they extravasate into the hypoxic tumor microenvironment. Their use can enhance the efficiency of tumor chemotherapy, radiotherapy, fluorescence and photoacoustic intensity, and other imaging and therapeutic strategies. By targeting the broad habitats of tumors, rather than tumor-specific receptors, this strategy has the potential to overcome the problem of tumor heterogeneity and could be used to design diagnostic and therapeutic nanoparticles for a broad range of solid tumors.

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Targeting tumor hypoxia with stimulus-responsive nanocarriers in overcoming drug resistance and monitoring anticancer efficacy

Cited by 46 publications

References 45 publications

Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications

Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications

Tumor-Microenvironment- Responsive Size-Shrinkable Drug-Delivery Nanosystems for Deepened Penetration Into Tumors

<p>Hypoxia-active nanoparticles used in tumor theranostic</p>

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