Doxorubicin-loaded pH-sensitive micelles: A promising alternative to enhance antitumor activity and reduce toxicity

Cavalcante, Carolina Henriques; Fernandes, Renata Salgado; Silva, Juliana de Oliveira; Oda, Caroline Mari Ramos; Leite, Elaine Amaral; Cassali, Geovanni Dantas; Charlie-Silva, Ives; Fernandes, Bianca Helena Ventura; Ferreira, Lucas Antônio Miranda; Barros, André Luís Branco de

doi:10.1016/j.biopha.2020.111076

Cited by 31 publications

(22 citation statements)

References 33 publications

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“…Micelles have excellent biocompatibility and can encapsulate a wide variety of drugs, and they preferentially accumulate in tumors via the EPR effect. That said, the nature of the copolymers used to prepare them and the surface charge, core-drug compatibility, drug loading capacity, drug release, and kinetics may affect the pharmacokinetic and distribution profile of the encapsulated drug [ 74 , 75 ].…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, the presence of a radionuclide highlighted that the efficacy of micelles was due to their accumulation in cell lines [ 74 ]. Similarly, the radiolabeling of pH-sensitive doxorubicin-loaded micelles let to evaluate their higher accumulation in tumor sites compared to non-targeted tissues [ 75 ]. However, micelles can be radiolabeled also with a therapeutical radionuclide.…”

Section: Resultsmentioning

confidence: 99%

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Nanoparticles and Radioisotopes: A Long Story in a Nutshell

et al. 2022

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The purpose of this narrative review was to assess the use of nanoparticles (NPs) to deliver radionuclides to targets, focusing on systems that have been tested in pre-clinical and, when available, clinical settings. A literature search was conducted in PubMed and Web of Science databases using the following terms: “radionuclides” AND “liposomes” or “PLGA nanoparticles” or “gold nanoparticles” or “iron oxide nanoparticles” or “silica nanoparticles” or “micelles” or “dendrimers”. No filters were applied, apart from a minimum limit of 10 patients enrolled for clinical studies. Data from some significant studies from pre-clinical and clinical settings were retrieved, and we briefly describe the information available. All the selected seven classes of nanoparticles were highly tested in clinical trials, but they all present many drawbacks. Liposomes are the only ones that have been tested for clinical applications, though they have never been commercialized. In conclusion, the application of NPs for imaging has been the object of much interest over the years, albeit mainly in pre-clinical settings. Thus, we think that, based on the current state, radiolabeled NPs must be investigated longer before finding their place in nuclear medicine.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Nanoparticles and Radioisotopes: A Long Story in a Nutshell

et al. 2022

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“…Several studies have already assessed the effects of Dox on zebrafish embryo development ( Yang et al, 2011 ; Chang et al, 2014 ; Han et al, 2015 ; Cavalcante et al, 2021 ), and its toxicity was demonstrated at different developmental stages ( Chang et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Evaluation of Sdox, a Promising H2S-Releasing Doxorubicin for the Treatment of Chemoresistant Tumors

et al. 2022

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Sdox is a hydrogen sulfide (H2S)-releasing doxorubicin effective in P-glycoprotein-overexpressing/doxorubicin-resistant tumor models and not cytotoxic, as the parental drug, in H9c2 cardiomyocytes. The aim of this study was the assessment of Sdox drug-like features and its absorption, distribution, metabolism, and excretion (ADME)/toxicity properties, by a multi- and transdisciplinary in silico, in vitro, and in vivo approach. Doxorubicin was used as the reference compound. The in silico profiling suggested that Sdox possesses higher lipophilicity and lower solubility compared to doxorubicin, and the off-targets prediction revealed relevant differences between Dox and Sdox towards several cancer targets, suggesting different toxicological profiles. In vitro data showed that Sdox is a substrate with lower affinity for P-glycoprotein, less hepatotoxic, and causes less oxidative damage than doxorubicin. Both anthracyclines inhibited CYP3A4, but not hERG currents. Unlike doxorubicin, the percentage of zebrafish live embryos at 72 hpf was not affected by Sdox treatment. In conclusion, these findings demonstrate that Sdox displays a more favorable drug-like ADME/toxicity profile than doxorubicin, different selectivity towards cancer targets, along with a greater preclinical efficacy in resistant tumors. Therefore, Sdox represents a prototype of innovative anthracyclines, worthy of further investigations in clinical settings.

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“…Anti-cancer effects or physicochemical properties can be improved via the modification of micelles or conjugation. Cavalcante et al developed pH-sensitive micelles in order to enhance antitumor activity and reduce toxicity [73]. DSPE-PEG 2000 , oleic acid, and DOX were used to manufacture micelles.…”

Section: Micellesmentioning

confidence: 99%

Pharmaceutical Aspects of Nanocarriers for Smart Anticancer Therapy

Hwang

Chakraborty

et al. 2021

Pharmaceutics

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Drug delivery to tumor sites using nanotechnology has been demonstrated to overcome the drawbacks of conventional anticancer drugs. Altering the surface shape and geometry of nanocomposites alters their chemical properties, which can confer multiple attributes to nanocarriers for the treatment of cancer and their use as imaging agents for cancer diagnosis. However, heterogeneity and blood flow in human cancer limit the distribution of nanoparticles at the site of tumor tisues. For targeted delivery and controlled release of drug molecules in harsh tumor microenvironments, smart nanocarriers combined with various stimuli-responsive materials have been developed. In this review, we describe nanomaterials for smart anticancer therapy as well as their pharmaceutical aspects including pharmaceutical process, formulation, controlled drug release, drug targetability, and pharmacokinetic or pharmacodynamic profiles of smart nanocarriers. Inorganic or organic-inorganic hybrid nanoplatforms and the electrospinning process have also been briefly described here.

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Doxorubicin-loaded pH-sensitive micelles: A promising alternative to enhance antitumor activity and reduce toxicity

Cited by 31 publications

References 33 publications

Nanoparticles and Radioisotopes: A Long Story in a Nutshell

Nanoparticles and Radioisotopes: A Long Story in a Nutshell

A Comprehensive Evaluation of Sdox, a Promising H2S-Releasing Doxorubicin for the Treatment of Chemoresistant Tumors

Pharmaceutical Aspects of Nanocarriers for Smart Anticancer Therapy

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