Tailor-Made Dual pH-Sensitive Polymer–Doxorubicin Nanoparticles for Efficient Anticancer Drug Delivery

Du, Jin‐Zhi; Du, Xiao-Jiao; Mao, Chengqiong; Wang, Jun

doi:10.1021/ja207150n

Cited by 1,093 publications

(788 citation statements)

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“…Stimuli-responsive Bsmart^nanoparticles that respond to heat, pH, enzyme activity, or magnetic fields have recently attracted great interest in biomedical research [23][24][25][26][27]. Few studies have explored the triggered release of nanoparticles mediated by an electric field [28,29].…”

Section: Discussionmentioning

confidence: 99%

Electroresponsive Nanoparticles Improve Antiseizure Effect of Phenytoin in Generalized Tonic-Clonic Seizures

et al. 2016

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Previously, we developed electroresponsive hydrogel nanoparticles (ERHNPs) modified with angiopep-2 (ANG) to facilitate the delivery of the antiseizure drug phenytoin sodium (PHT). However, the electroresponsive characteristics were not verified directly in epileptic mice and the optimal preparation formula for electroresponsive ability is still unclear. Here, we further synthesized PHT-loaded ANG-ERHNPs (ANG-PHT-HNPs) and PHT-loaded nonelectroresponsive hydrogel nanoparticles (ANG-PHTHNPs) by changing the content of sodium 4-vinylbenzene sulfonate in the preparation formulae. In vivo microdialysis analysis showed that ANG-PHT-ERHNPs not only have the characteristics of a higher distribution in the central nervous system, but also have electroresponsive ability, which resulted in a strong release of nonprotein-bound PHT during seizures.In both electrical-(maximal electrical shock) and chemicalinduced (pentylenetetrazole and pilocarpine) seizure models, ANG-PHT-ERHNPs lowered the effective therapeutic doses of PHT and demonstrated the improved antiseizure effects compared with ANG-PHT-HNPs or PHT solution. These results demonstrate that ANG-ERHNPs are able to transport PHT into the brain efficiently and release them when epileptiform activity occurred, which is due to the content of sodium 4-vinylbenzene sulfonate in formula. This may change the therapeutic paradigm of existing drug treatment for epilepsy into a type of on-demand control for epilepsy in the future.

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Section: Discussionmentioning

confidence: 99%

Electroresponsive Nanoparticles Improve Antiseizure Effect of Phenytoin in Generalized Tonic-Clonic Seizures

et al. 2016

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“…This suggests also that NPs can reduce premature drug release during circulation but specifically enhance intracellular drug release, which will be an important feature in cancer treatment [14].…”

Section: Polyethylene Glycolmentioning

confidence: 99%

“…It was also proved that NPs strongly induced autophagy and potentially led to autophagic cell death. In Doxorubicin (12), a widely used anticancer drug, was involved in the formation of a dual pHsensitive polymer conjugate [14]. Doxorubicin was linked to PEG through an acid-labile hydrazone bond.…”

Section: Page 13 Of 25mentioning

confidence: 99%

“…Semaxanib (14) and sunitinib (15) are multitarget tyrosine kinase inhibitors but they have some side effects such as cardiotoxicity, severe cutaneous toxicities and hematotoxicity. The NPs obtained by the covalent linkage of these compounds with squalene were biologically evaluated on human umbilical vein endothelial cells (HUVECs), demonstrating that squalenoyl-sunitinib conjugate NPs showed notable cytotoxicity whereas semaxanib NPs were not active [19].…”

Section: Page 13 Of 25mentioning

confidence: 99%

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Self-assembly drug conjugates for anticancer treatment

Fumagalli

Marucci

Christodoulou

et al. 2016

Drug Discovery Today

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Please cite this article as: Fumagalli, G., Marucci, C., Christodoulou, M.S., Stella, B., Dosio, F., Passarella, D.,Self-assembly drug conjugates for anticancer treatment, Drug Discovery Today (2016), http://dx.doi.org/10.1016/j.drudis. 2016.06.018 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t Keywords: Self-assembly; drug conjugate; nanoparticle. Self-assembly drug conjugates for anticancer treatmentTeaser: In this review we summarize the recent advances in nanoparticles obtained by self-assembly drug conjugates, a useful tool to improve drug delivery of anticancer compounds. Page 4 of 25A c c e p t e d M a n u s c r i p tSelf-assembly drug conjugate preparation is a promising approach to improve activity and penetration through physiological barriers of potent small molecules, as well as to reduce any side effects. Drug conjugates can self-assemble in water to form nanoparticles (NPs) that offer several advantages because: (i) they are easy to obtain; (ii) they can reach high local drug concentration in tumor tissues; and (iii) they can reduce the side effects of drugs. All these factors improve drug pharmacokinetic properties. Here, we have reviewed the scope of nanotechnology-based self-assembly drug delivery approaches focusing on prodrugs able to form NPs by self-assembly; we have also summarized the current perspective and challenges facing the successful treatment of cancer.

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“…The covalent linkage of folate served to recognise the cancer site and the pH-sensitive DOx bonds delivered effective release of the drug at the tumour site. [10] The SPION core of the module was chosen for its super paramagnetic properties, [11] which facilitates non-invasive visualisation via magnetic resonance imaging. Flexible surface properties further enrich the current state of the art by core-shell nanoassembly.…”

Section: Introductionmentioning

confidence: 99%

MRI‐Visual Order–Disorder Micellar Nanostructures for Smart Cancer Theranostics

Khaliq

Romu

Wiecheć

et al. 2013

Adv Healthcare Materials

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This development of MRI-visual order-disorder structures for cancer nanomedicine explores pH-trigger mechanism for theragnosis of tumour hallmark functions. Superparamagnetic iron oxide nanoparticles (SPIONs) stabilised with amphiphilic poly(styrene)-b-poly(acrylic acid)-doxorubicin with folic acid (FA) surfacing is employed as a multi-functional approach to specifically target, diagnose and deliver drugs via a single nanoscopic platform for cancer therapy. The functional aspects of the micellar nanocomposite is investigated in vitro using human breast SkBr3 and colon cancer HCT116 cell lines for the delivery, release, localisation and anticancer activity of the drug. Our work shows, for the first time, concentration dependent T 2 -weighted MRI contrast for a monolayer of clustered cancer cells. The pH tunable order-disorder transition of the core-shell structure induces the relative changes in MRI contrast. The outcomes elucidate the potential of this material for smart cancer theranostics by delivering non-invasive real-time diagnosis, targeted therapy and monitoring the course and response of the action before, during and after the treatment regimen.Submitted to 3

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Tailor-Made Dual pH-Sensitive Polymer–Doxorubicin Nanoparticles for Efficient Anticancer Drug Delivery

Cited by 1,093 publications

References 40 publications

Electroresponsive Nanoparticles Improve Antiseizure Effect of Phenytoin in Generalized Tonic-Clonic Seizures

Electroresponsive Nanoparticles Improve Antiseizure Effect of Phenytoin in Generalized Tonic-Clonic Seizures

Self-assembly drug conjugates for anticancer treatment

MRI‐Visual Order–Disorder Micellar Nanostructures for Smart Cancer Theranostics

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