Inorganic phosphate-triggered release of anti-cancer arsenic trioxide from a self-delivery system: an in vitro and in vivo study

Chen, Fei Yan; Yi, Jing; Gu, Zhe Jia; Tang, Bin; Li, Jian Qi; Li, Li; Kulkarni, P. V.; Liu, Li; Mason, Ralph P.; Tang, Qun

doi:10.1039/c6nr00536e

Cited by 16 publications

(14 citation statements)

References 31 publications

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“…As 2 O 3 , a kind of traditional Chinese medicine, had been approved as frontline treatment for APL by FDA for many years. It could also be used in other solid cancer, such as liver cancer, prostate cancer, cervical cancer and breast cancer [9,[12][13][14][15][16][17][18]. However, its clinical application is somehow limited owing to its high toxicity to the normal tissues.…”

Section: Discussionmentioning

confidence: 99%

Arsenic trioxide nanoparticles inhibit acute promyelocytic leukemia cell proliferation and induce apoptosis via PTEN/AKT signalling pathway

Wang¹,

Dong²,

Liu³

et al. 2018

biomedicalresearch

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Background: Arsenic Trioxide (As 2 O 3) is a FDA-approved agent for the treatment of Acute Promyelocytic Leukemia (APL). But the high-toxicity is a bottleneck of the effect of As 2 O 3. Methods: In our previous work, we made a novel nanoparticle formulation of As 2 O 3. The aim of the present study was to preliminary study the possible mechanisms of the antitumor effect of As 2 O 3 nanoparticles on NB4 cells. We examined the proliferation and apoptosis of NB4 cells incubated with the As 2 O 3 or As 2 O 3 nanoparticles. Protein levels of p-PTEN, p-AKT, Bax, caspase-3, caspase-9 and AIF of NB4 cells after using As 2 O 3 nanoparticles and traditional As 2 O 3 were determined by Western blotting analysis. Results: In vitro cytotoxicity test showed that the inhibition rate and apoptosis level of NB4 cells treated with As 2 O 3 nanoparticles was much higher than that of traditional As 2 O 3. Moreover, As 2 O 3 nanoparticles resulted in a more significant increase in p-PTEN expression and a greater reduction in p-Akt expression compared with traditional As 2 O 3. Conclusions: Our findings indicated the obvious anticancer effect of As 2 O 3 nanoparticles and demonstrate the possible mechanism of its therapeutic potential. The results provide a foundation for the future clinical studies of As 2 O 3 nanoparticles in APL patients.

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Section: Discussionmentioning

confidence: 99%

Arsenic trioxide nanoparticles inhibit acute promyelocytic leukemia cell proliferation and induce apoptosis via PTEN/AKT signalling pathway

Wang¹,

Dong²,

Liu³

et al. 2018

biomedicalresearch

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“…By contrast, Chen et al 60 achieved enhanced arsenic accumulation in the tumor via a different mechanism. Their Pi-triggered nanoparticles showed a 10-fold accumulation of arsenic in the tumor tissue compared to free ATO, which they ascribed to the EPR effect of nanoparticles.…”

Section: Controlled Release Of Atomentioning

confidence: 95%

“…All four studies following this approach [60][61][62]93 used gadolinium-based nanoparticles, in which the arsenic could be exchanged by phosphate ions. Chen et al 60 reported an outstanding ON/OFF specificity for their GdAsO x nanoparticles, with no arsenic release in the absence of Pi in vitro. Fu et al 61 and Zhao et al 62 attempted to introduce Pi-triggered ATO drug-eluting beats (DEBs) for the improvement of TACE therapy (see below) for HCC.…”

Section: Controlled Release Of Atomentioning

confidence: 99%

“…Inorganic phosphate (Pi-)triggered ATO release was another way of obtaining controllable release. All four studies following this approach [60][61][62]93 used gadolinium-based nanoparticles, in which the arsenic could be exchanged by phosphate ions. Chen et al 60 reported an outstanding ON/OFF specificity for their GdAsO x nanoparticles, with no arsenic release in the absence of Pi in vitro.…”

Section: Controlled Release Of Atomentioning

confidence: 99%

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Current status and future prospects of nanomedicine for arsenic trioxide delivery to solid tumors

Sönksen

Kerl

Bunzen

2021

Medicinal Research Reviews

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Despite having a rich history as a poison, arsenic and its compounds have also gained a great reputation as promising anticancer drugs. As a pioneer, arsenic trioxide has been approved for the treatment of acute promyelocytic leukemia. Many in vitro studies suggested that arsenic trioxide could also be used in the treatment of solid tumors. However, the transition from bench to bedside turned out to be challenging, especially in terms of the drug bioavailability and concentration reaching tumor tissues. To address these issues, nanomedicine tools have been proposed. As nanocarriers of arsenic trioxide, various materials have been examined including liposomes, polymer, and inorganic nanoparticles, and many other materials. This review gives an overview of the existing strategies of delivery of arsenic trioxide in cancer treatment with a focus on the drug encapsulation approaches and medicinal impact in the treatment of solid tumors. It focuses on the progress in the last years and gives an outlook and suggestions for further improvements including theragnostic approaches and targeted delivery.

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“…In order to solve the above problems in clinical application, numerous nano preparations such as liposomes and nanoparticles have been reported [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] . However, these nanomedicines are still confronted with challenges in clinical transformation, such as low drug loading, complicated preparation processes and difficulty in co-loaded ATO and ATRA.…”

Section: Introductionmentioning

confidence: 99%

A practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia

Liu

Yin

Widjaya

et al. 2021

Asian Journal of Pharmaceutical Sciences

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Arsenic trioxide (ATO) combined with all trans retinoic acid (ATRA) is the first choice for the treatment of low and medium risk acute promyelocytic leukemia (APL). Clinical studies reported that the combination of ATO and ATRA could achieve a significant curative effect. However, the retinoic acid syndrome, serious drug resistance and the short half-life in vivo which lead to frequent and large dose administration limit the application of ATRA. In addition, the preparations of arsenic are conventional injections and tablets in clinic, which has poor patients' compliance caused by frequent long-term administration and serious side effects. In order to overcome the above limitations, a phospholipid phase separation gel (PPSG) loaded with ATO and ATRA was developed. ATO+ATRA-PPSG (AAP), as a biodegradable sustained-release delivery system, was the first achievement of co-delivery of hydrophilic ATO and lipophilic ATRA with high drug loading which is the main problem in the application of nano preparation. The prepared PPSG displayed high safety and biocompatibility. The drug in PPSG was released slowly and continuously in vivo and in vitro for up to 10 d, which could reduce the side effects caused by the fluctuation of blood drug concentration and solve the problem of the long treatment cycle and frequent administration. In vivo pharmacokinetics depicted that PPSG could improve the bioavailability, decrease the peak concentration, and prolong the t 1/2 of ATO and ATRA. Particularly, AAP significantly inhibited the tumor volume, extended the survival period of tumor-bearing mice, and promoted the differentiation of APL cells into normal cells. Therefore, ATO+ATRA-PPSG not only could co-load hydrophilic ATO and lipophilic ATRA according to the clinical dosage, but also possessed the sustained-release and long-acting treatment effect which was expected to reduce administration time and ameliorate compliance of patients. Thus, it had great potential for clinical transformation and application.

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Inorganic phosphate-triggered release of anti-cancer arsenic trioxide from a self-delivery system: an in vitro and in vivo study

Cited by 16 publications

References 31 publications

Arsenic trioxide nanoparticles inhibit acute promyelocytic leukemia cell proliferation and induce apoptosis via PTEN/AKT signalling pathway

Arsenic trioxide nanoparticles inhibit acute promyelocytic leukemia cell proliferation and induce apoptosis via PTEN/AKT signalling pathway

Current status and future prospects of nanomedicine for arsenic trioxide delivery to solid tumors

A practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia

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