A nanogel of on-site tunable pH-response for efficient anticancer drug delivery

Zhou, Ting; Xiao, Chuanfu; Fan, Jiao Rong; Chen, Shoumin; Shen, Jing; Wu, Weitai; Zhou, Shuiqin

doi:10.1016/j.actbio.2012.08.017

Cited by 96 publications

(49 citation statements)

References 51 publications

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“…Vesicle encapsulated 5-fluorouracil has been seen to have a reduced in vivo toxicity when used in combination with other anticancer therapies (30). In vivo studies were not conducted in this study, but it is possible that encapsulation of 5-fluorouracil with Pheroid™ may result in reduced toxicity and in turn reduced side effect profile.…”

Section: Drug Efficacy Testingmentioning

confidence: 76%

Topical Delivery of 5-Fluorouracil from Pheroid™ Formulations and the In Vitro Efficacy Against Human Melanoma

et al. 2015

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Abstract. Drug delivery vehicles can influence the topical delivery and the efficacy of an active pharmaceutical ingredient (API). In this study, the influence of Pheroid™ technology, which is a unique colloidal drug delivery system, on the skin permeation and antimelanoma efficacy of 5-fluorouracil were investigated. Lotions containing Pheroid™ with different concentrations of 5-fluorouracil were formulated then used in Franz cell skin diffusion studies and tape stripping. The in vitro efficacy of 5-fluorouracil against human melanoma cells (A375) was investigated using a flow cytometric apoptosis assay. Statistically significant concentrations of 5-fluorouracil diffused into and through the skin with Pheroid™ formulations resulting in an enhanced in vitro skin permeation from the 4.0% 5-fluorouracil lotion (p<0.05). The stratum corneum-epidermis and epidermis-dermis retained 5-fluorouracil concentrations of 2.31 and 6.69 μg/ml, respectively, after a diffusion study with the 4.0% Pheroid™ lotion. Subsequent to the apoptosis assay, significant differences were observed between the effect of 13.33 μg/ml 5-fluorouracil in Pheroid™ lotion and the effects of the controls. The results obtained suggest that the Pheroid™ drug delivery system possibly enhances the flux and delivery of 5-fluorouracil into the skin. Therefore, using Pheroid™ could possibly be advantageous with respect to topical delivery of 5-fluorouracil.

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Section: Drug Efficacy Testingmentioning

confidence: 76%

Topical Delivery of 5-Fluorouracil from Pheroid™ Formulations and the In Vitro Efficacy Against Human Melanoma

et al. 2015

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“…14 Currently, several studies have demonstrated that the acidic condition in the tumor site is a promising means of eliciting drug release. [15][16][17][18] And, in our work, we found that drug molecules of Pt were preferentially released from the nanodrug in acidic conditions compared with the normal physical condition.…”

Section: Introductionmentioning

confidence: 63%

“…This pH-sensitive Pt-release behavior is very important for "smart" drug carriers since many pathological environments in tumor tissues, intracellular lysosomes, and endosomes have a lower pH than in normal tissues and cells. 16,33 To improve the stability of GQDs in physiological solution, GQDs were sonicated into smaller pieces. Four-armed PEG-amine was conjugated to the carboxylic acid groups on GQDs-Pt via amide formation.…”

Section: Ph-dependent Release Of Ptmentioning

confidence: 99%

Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma

Zheng¹,

Yin²,

Cai³

et al. 2018

IJN

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Background Tumor microenvironment plays an important role in the chemoresistance of oral squamous cell carcinoma (OSCC). Hypoxia in the microenvironment is one of the important factors that contributes to OSCC chemoresistance; therefore overcoming hypoxia-mediated chemoresistance is one of the great challenges in clinical practice. Methods In this study, we developed a drug delivery system based on Pt-loaded, polyethylene glycol-modified graphene quantum dots via chemical oxidation and covalent reaction. Results Our results show that synthesized polyethylene glycol-graphene quantum dots-Pt (GPt) is about 5 nm in diameter. GPt sensitizes OSCC cells to its treatment in both normoxia and hypoxia conditions. Inductively coupled plasma-mass spectrometry assay shows that GPt enhances Pt accumulation in cells, which leads to a notable increase of S phase cell cycle arrest and apoptosis of OSCC cells in both normoxia and hypoxic conditions. Finally, compared with free cisplatin, GPt exhibits a strong inhibitory effect on the tumor growth with less systemic drug toxicity in an OSCC xenograft mouse tumor model. Conclusion Taken together, our results show that GPt demonstrates superiority in combating hypoxia-induced chemoresistance. It might serve as a novel strategy for future microenvironment-targeted cancer therapy.

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“…For example, Engleman has developed a low pH inserting peptide, pHLIP, that has been used to develop molecular imaging agents as well as a targeting moiety to distribute chemotherapeutics to low pH regions [39][40][41]. Additionally, whole families of pH-sensitive nanoparticles, nanogels, liposomes and micelles have been developed to release their chemotherapeutic payloads only under acidic conditions [42][43][44][45][46][47][48]. This is a very dynamic area of research, which has shown dramatic anti-tumour effects.…”

Section: (A) Exploiting Tumour Aciditymentioning

confidence: 99%

Targeting ion transport in cancer

Oosterwijk

Gillies

2014

Phil. Trans. R. Soc. B

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The metabolism of cancer cells differs substantially from normal cells, including ion transport. Although this phenomenon has been long recognized, ion transporters have not been viewed as suitable therapeutic targets. However, the acidic pH values present in tumours which are well outside of normal limits are now becoming recognized as an important therapeutic target. Carbonic anhydrase IX (CAIX) is fundamental to tumour pH regulation. CAIX is commonly expressed in cancer, but lowly expressed in normal tissues and that presents an attractive target. Here, we discuss the possibilities of exploiting the acidic, hypoxic tumour environment as possible target for therapy. Additionally, clinical experience with CAIX targeting in cancer patients is discussed.

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A nanogel of on-site tunable pH-response for efficient anticancer drug delivery

Cited by 96 publications

References 51 publications

Topical Delivery of 5-Fluorouracil from Pheroid™ Formulations and the In Vitro Efficacy Against Human Melanoma

Topical Delivery of 5-Fluorouracil from Pheroid™ Formulations and the In Vitro Efficacy Against Human Melanoma

Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma

Targeting ion transport in cancer

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