Stimuli-responsive cross-linked micelles for on-demand drug delivery against cancers

Li, Yuanpei; Xiao, Kai; Zhu, Wei; Deng, Wenbin; Lam, Kit S.

doi:10.1016/j.addr.2013.09.008

Cited by 270 publications

(171 citation statements)

References 79 publications

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“…For example, crosslinked micelles often release their drug contents in a sustained manner, which might not provide tumors with sufficiently cytotoxic local drug concentrations. To improve the overall therapeutic efficacy by inducing and facilitating tumor-specific drug release, stimulus-responsive crosslinked micelles have recently been introduced [9,10]. These micelles can be tailored to respond to a particular physiological stimulus that differentiates tumors from normal tissue.…”

Section: Introductionmentioning

confidence: 99%

In situ diselenide-crosslinked polymeric micelles for ROS-mediated anticancer drug delivery

et al. 2016

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Section: Introductionmentioning

confidence: 99%

In situ diselenide-crosslinked polymeric micelles for ROS-mediated anticancer drug delivery

et al. 2016

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“…This may be resulted from the fact that the CCMs remained intact during the circulation, 38,53 and achieved rapid release in response to the GSH stimulus at the tumor sites. Therefore, FA-CCM-Cur, which combined folate receptor-mediated active targeting drug delivery with the stable drug delivery during circulation endowed by the core cross-linking, showed the highest (at all the time points) and the longest (even 48 hours after injection) Cur accumulation in tumor.…”

Section: Ex Vivo Distribution and Tumor Accumulationsmentioning

confidence: 99%

Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

Zhou¹,

Yang²,

Wang³

et al. 2016

IJN

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Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation.

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“…For the practical applications of stimuli-responsive nanocarriers for intracellular drug delivery, it is a promising strategy to design and develop smart polymeric micelles which can respond to the intracellular environment, such as pH, temperature, and so on [26]. Recently, an effective approach has been to incorporate cleavable links into the polymer structure, either to cause a structural change of the delivery systems, or to direct conjugate drug molecules which could be released on the cleavage of the links [27].…”

Section: Introductionmentioning

confidence: 99%

Synthesis strategies for disulfide bond-containing polymer-based drug delivery system for reduction-responsive controlled release

Liu

2015

Front. Mater. Sci.

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Tumor micro-environment responsive drug delivery systems (DDSs) have been developed as a potential approach to reduce the side effects of cancer chemotherapy. Glutathione (GSH) has been supposed to the most significant signal of the difference between the normal tissue and the tumor cells, besides the media pH and temperature. In recent years, the reduction-responsive DDSs have attracted more and more attention for delivery of anti-cancer drugs, based on such physiological signal. Among them, disulfide bond-containing polymers have been designed as the main tool for the purpose. The recent progress in the synthesis strategies for the disulfide bondcontaining polymer-based DDS is focused in the present review.

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Stimuli-responsive cross-linked micelles for on-demand drug delivery against cancers

Cited by 270 publications

References 79 publications

In situ diselenide-crosslinked polymeric micelles for ROS-mediated anticancer drug delivery

In situ diselenide-crosslinked polymeric micelles for ROS-mediated anticancer drug delivery

Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

Synthesis strategies for disulfide bond-containing polymer-based drug delivery system for reduction-responsive controlled release

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