A glance over doxorubicin based-nanotherapeutics: From proof-of-concept studies to solutions in the market

Gonçalves, Mara; Mignani, Serge; Rodrigues, João; Tomás, Helena

doi:10.1016/j.jconrel.2019.11.016

Cited by 65 publications

(40 citation statements)

References 329 publications

(312 reference statements)

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“…Moreover, although Doxil ® improves the pharmacokinetic properties of DOX, it does not increase the pharmacological efficacy of DOX because of the insufficient cell uptake of liposomes [30]. In this context, other types of DOX nanocarriers have been proposed [31], such as poly(lactic-co-glycolic acid) (PLGA) nanoparticles [32], solid lipid nanoparticles [33] or nanosponges with different structures [34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Improvement in the Anti-Tumor Efficacy of Doxorubicin Nanosponges in In Vitro and in Mice Bearing Breast Tumor Models

Argenziano

Gigliotti

Clemente

et al. 2020

Cancers

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Doxorubicin (DOX) is an anthracycline widely used in cancer therapy and in particular in breast cancer treatment. The treatment with DOX appears successful, but it is limited by a severe cardiotoxicity. This work evaluated the in vitro and in vivo anticancer effect of a new formulation of β-cyclodextrin nanosponges containing DOX (BNS-DOX). The BNS-DOX effectiveness was evaluated in human and mouse breast cancer cell lines in vitro in terms of effect on cell growth, cell cycle distribution, and apoptosis induction; and in vivo in BALB-neuT mice developing spontaneous breast cancer in terms of biodistribution, cancer growth inhibition, and heart toxicity. BNS-DOX significantly inhibited cancer cell proliferation, through the induction of apoptosis, with higher efficiency than free DOX. The breast cancer growth in BALB-neuT mice was inhibited by 60% by a BNS-DOX dose five times lower than the DOX therapeutic dose, with substantial reduction of tumor neoangiogenesis and lymphangiogenesis. Biodistribution after BNS-DOX treatment revealed a high accumulation of DOX in the tumor site and a low accumulation in the hearts of mice. Results indicated that use of BNS may be an efficient strategy to deliver DOX in the treatment of breast cancer, since it improves the anti-cancer effectiveness and reduces cardiotoxicity.

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Section: Discussionmentioning

confidence: 99%

Improvement in the Anti-Tumor Efficacy of Doxorubicin Nanosponges in In Vitro and in Mice Bearing Breast Tumor Models

Argenziano

Gigliotti

Clemente

et al. 2020

Cancers

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“…In the last years, graphene-based materials (G) due to their outstanding physicochemical properties have been proposed for promising biomedical/pharmaceutical applications, such as bio-imaging, drug/gene delivery, and biomolecular detection [ 1 , 2 , 3 ]. Numerous studies have been dedicated to the development and the biological response of G-based nanocarriers loaded with Doxorubicin (DOX), an effective chemotherapeutic agent used for the treatment of different kind of cancer [ 4 , 5 , 6 ]. Generally, literature data demonstrated superior therapeutic performance in cancer chemotherapy experiments, both in vitro and in vivo, due to the improved tissue penetration and cellular uptake of G-based nanocarriers [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration

Caccamo¹,

Currò²,

Ientile³

et al. 2020

IJMS

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The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we investigated the intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter™ platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD@DOX (25 µg/mL) compared with untreated cells. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. The reliable advantages provided by NanoString® technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field.

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“…The nanotechnological approach may be a promising solution. In fact, a liposomal doxorubicin nanoformulation (Doxil®) is on the market but much research is still focused on the design of nanocarriers for the delivery of doxorubicin to tumor cells [22][23][24][25][26][27] .…”

Section: Discussionmentioning

confidence: 99%

Albumin nanoformulations as an innovative solution to overcome doxorubicin chemoresistance

Bessone¹,

Dianzani²,

Argenziano³

et al. 2020

CDR

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Aim: Resistance to chemotherapy is a major limiting factor that hamper the effectiveness of anticancer therapies. Doxorubicin is an antineoplastic agent used in the treatment of a wide range of cancers. However, it presents several limitations such as dose-dependent cardiotoxicity, lack of selectivity for tumor cells, and induced cell resistance. Nanotechnology represents a promising strategy to avoid these drawbacks. In this work, new albumin-based nanoparticles were formulated for the intracellular delivery of doxorubicin with the aim to overcome cancer drug resistance. Methods: Glycol chitosan-coated and uncoated albumin nanoparticles were prepared with a tuned coacervation method. The nanoformulations were in vitro characterized evaluating the physicochemical parameters, morphology, and in vitro release kinetics. Biological assays were performed on A2780res and EMT6 cells from human ovarian carcinoma and mouse mammary cell lines resistant for doxorubicin, respectively. Results: Cell viability assays showed that nanoparticles have higher cytotoxicity than the free drug. Moreover, at low concentrations, both doxorubicin-loaded nanoparticles inhibited the cell colony formation in a greater extent than drug solution. In addition, the cell uptake of the different formulations was investigated by confocal microscopy and by the HPLC determination of doxorubicin intracellular accumulation. The nanoparticles were rapidly internalized in greater extent compared to the free drug. Conclusion: Based on these results, doxorubicin-loaded albumin nanoparticles might represent a novel platform to overcome the mechanism of drug resistance in cancer cell lines and improve the drug efficacy.

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A glance over doxorubicin based-nanotherapeutics: From proof-of-concept studies to solutions in the market

Cited by 65 publications

References 329 publications

Improvement in the Anti-Tumor Efficacy of Doxorubicin Nanosponges in In Vitro and in Mice Bearing Breast Tumor Models

Improvement in the Anti-Tumor Efficacy of Doxorubicin Nanosponges in In Vitro and in Mice Bearing Breast Tumor Models

Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration

Albumin nanoformulations as an innovative solution to overcome doxorubicin chemoresistance

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