Tumor targeting and microenvironment-responsive nanoparticles for gene delivery

Huang, Shixian; Shao, Kun; Kuang, Yuyang; Liu, Yang; Li, Jianfeng; An, Sai; Guo, Yubo; Ma, Haojun; He, Xi; Jiang, Chen

doi:10.1016/j.biomaterials.2013.03.043

Cited by 119 publications

(80 citation statements)

References 41 publications

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“…As an alternative to aim at neovascular alone, the dual-targeting strategy, combining anti-neovascular therapy with glioma cells-oriented therapy, may offer a more promising therapeutic strategy because it not only chokes the blood supply and starves the glioma cells of nutrients and oxygen but also kills glioma cells directly [5,6], holds great potential in reducing those side effects of anti-neovascular mentioned above. However, rare study on the effective combination treatment for glioma has been reported [7] and most related research in the field of combined tumor therapy focuses on delivering two agents with different functions [5,7] or aiming at two kinds of target sites [8,9]. And thus a drug delivery system with dual-therapeutic effect for glioma treatment via simple design is still urgently needed.…”

Section: Introductionmentioning

confidence: 99%

EGFP–EGF1-conjugated nanoparticles for targeting both neovascular and glioma cells in therapy of brain glioma

et al. 2014

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Section: Introductionmentioning

confidence: 99%

EGFP–EGF1-conjugated nanoparticles for targeting both neovascular and glioma cells in therapy of brain glioma

et al. 2014

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“…Therapeutics, such as monoclonal antibodies and small interfering RNA (siRNA), are well suited to target tumor cells or specific genes but are associated with an increased risk of adverse immune reactions [2, 3] and ineffective delivery to cells [4]. New treatments based on the targeted delivery of therapeutic agents to the tumor microenvironment [5] rely on nanoparticles (NP) able encapsulate poorly soluble drugs [6], to provide protection from degradation [7], to enhance cellular internalization [8], or to trigger the release of payloads based on environmental cues [9]. NP can persist in blood circulation and exploit the enhanced permeability and retention (EPR) effect exhibited by tumor-associated blood vessels [10, 11].…”

Section: Introductionmentioning

confidence: 99%

The effect of multistage nanovector targeting of VEGFR2 positive tumor endothelia on cell adhesion and local payload accumulation

et al. 2014

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Nanovectors are a viable solution to the formulation of poorly soluble anticancer drugs. Their bioaccumulation in the tumor parenchyma is mainly achieved exploiting the enhanced permeability and retention (EPR) effect of the leaky neovasculature. In this paper we demonstrate that multistage nanovectors (MSV) exhibit rapid tumoritropic homing independent of EPR, relying on particle geometry and surface adhesion. By studying endothelial cells overexpressing vascular endothelial growth factor receptor-2 (VEGFR2), we developed MSV able to preferentially target VEGFR2 expressing tumor-associated vessels. Static and dynamic targeting revealed that MSV conjugated with anti-VEGFR2 antibodies displayed greater than a 4-fold increase in targeting efficiency towards VEGFR2 expressing cells while exhibiting minimal adherence to control cells. Additionally, VEGFR2 conjugation bestowed MSV with a significant increase in breast tumor targeting and in the delivery of a model payload while decreasing their accumulation in the liver. Surface functionalization with an anti-VEGFR2 antibody provided enhanced affinity towards the tumor vascular endothelium, which promoted enhanced adhesion and tumoritropic accumulation of a reporter molecule released by the MSV.

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“…10,11 Therefore, the physiological conditions of tumors and inflammatory tissues can be used strategically to selectively target nanotherapeutics with increased affinity for an acidic pH microenvironment (ie, 5.8-7.2) compared with the neutral pH of healthy tissues (ie, 7.0-7.4). [12][13][14][15] Importantly, an acidic pH has also been found inside membrane-bound organelles (eg, endosomes and lysosomes) and generally enables metabolic degradation of nonself compounds and microorganisms. [16][17][18] An acidic pH can also modulate the release kinetics of drugs and genetic materials loaded into pH-sensitive nanotherapeutics and provide a novel approach to prepare pH-responsive nonionic surfactant nanotherapeutics for treating inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

Ammonium glycyrrhizinate-loaded niosomes as a potential nanotherapeutic system for anti-inflammatory activity in murine models

Marianecci¹,

Rinaldi²,

Marzio³

et al. 2014

IJN

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Background: Liquorice extracts demonstrate therapeutic efficacy in treating dermatitis, eczema, and psoriasis when compared with corticosteroids. In this work, nonionic surfactant vesicles (niosomes, NSVs) containing polysorbate 20 (Tween 20), cholesterol, and cholesteryl hemisuccinate at different molar concentrations were used to prepare monoammonium glycyrrhizinate (AG)-loaded NSVs. The anti-inflammatory properties of AG-loaded NSVs were investigated in murine models. Methods: The physicochemical properties of the NSVs were characterized using dynamic light scattering. The fluidity of the lipid bilayer was evaluated by measuring the fluorescence intensity of diphenylhexatriene. The drug entrapment efficiency of AG was assessed using high-performance liquid chromatography. The physicochemical stability of the NSVs was evaluated as a function of time using dynamic light scattering combined with Turbiscan Lab(R) Expert analysis. Serum stability was determined by incubating the NSVs with 10% v/v fetal bovine serum. The cytotoxic effects of the NSVs were investigated in human dermal fibroblasts using the Trypan blue dye exclusion assay (for cell mortality) and an MTT assay (for cell viability). Release profiles for the AG-loaded NSVs were studied in vitro using cellulose membranes. NSVs showing the most desirable physicochemical properties were selected to test for in vivo anti-inflammatory activity in murine models. The anti-inflammatory activity of the NSVs was investigated by measuring edema and nociception in mice stimulated with chemical agents. Results: NSVs showed favorable physicochemical properties for in vitro and in vivo administration. In addition, they demonstrated long-term stability based on Turbiscan Lab Expert analysis. The membrane fluidity of the NSVs was not affected by self-assembling of the surfactants into colloidal structures. Fluorescence anisotropy was found to be independent of the molar ratios of cholesteryl hemisuccinate and/or cholesterol during preparation of the NSVs. The anti-inflammatory AG drug showed no effect on the stability of the NSVs. In vivo experiments demonstrated that AG-loaded NSVs decreased edema and nociceptive responses when compared with AG alone and empty NSVs. In vitro and in vivo results demonstrated that pH sensitive and neutral NSVs show no statistical significant difference. Conclusion: NSVs were nontoxic and showed features favorable for potential administration in vivo. In addition, neutral NSVs showed signs of increased anti-inflammatory and anti-nociceptive responses when compared with AG

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Tumor targeting and microenvironment-responsive nanoparticles for gene delivery

Cited by 119 publications

References 41 publications

EGFP–EGF1-conjugated nanoparticles for targeting both neovascular and glioma cells in therapy of brain glioma

EGFP–EGF1-conjugated nanoparticles for targeting both neovascular and glioma cells in therapy of brain glioma

The effect of multistage nanovector targeting of VEGFR2 positive tumor endothelia on cell adhesion and local payload accumulation

Ammonium glycyrrhizinate-loaded niosomes as a potential nanotherapeutic system for anti-inflammatory activity in murine models

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