Multifunctional ATRP based pH responsive polymeric nanoparticles for improved doxorubicin chemotherapy in breast cancer by proton sponge effect/endo-lysosomal escape

Lale, Shantanu V.; Kumar, Arun; Naz, Farhat; Bharti, Alok C.; Koul, Veena

doi:10.1039/c4py01698j

Cited by 53 publications

(31 citation statements)

References 56 publications

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“…2A clearly proved the formation of initiator, which was in agreement with above results in Fig. All these results 45 provided further evidence that poly(PEGMA) had been immobilized onto the surface of GCC NPs. The peaks of C1s with the binding energies at 285.5 and 284.5 eV corresponded to the sp3 and sp2 hybridized carbon atoms, while the peak at a higher binding energy of 287 eV was ascribed to the carbon atoms bound to oxygen (Fig.…”

supporting

confidence: 90%

“…6A-C, after four hours incubation with HeLa cells using GCC-poly(PEGMA) of 20 µg mL −1 , only weak fluorescence images of cells can be obtained, suggesting a small number of GCC-poly(PEGMA) being internalized. 45 The fluorescence stability of GCC-poly(PEGMA) in PBS was determined to be outstanding as shown in Fig. 6G-I).…”

Section: Cellular Imaging Of Gcc-poly(pegma)mentioning

confidence: 92%

“…First the red fluorescent GCC NPs 30 were facilely prepared by water in oil microemulsion method, and then the amino groups and hydroxyl groups on GCC NPs surface were modified with 2-bromoisobutyryl bromide to get the GCC-Br, which was employed as the nanoparticles initiator in ATRP system to finally obtain the GCC-35 poly(PEGMA) conjugates (Scheme 1). [44][45][46][47] The 40 fluorescence property, morphology, and stability of GCCpoly(PEGMA) were further characterized by fluorescence spectrum, transmission electron microscopy, and dynamic light scattering. [44][45][46][47] The 40 fluorescence property, morphology, and stability of GCCpoly(PEGMA) were further characterized by fluorescence spectrum, transmission electron microscopy, and dynamic light scattering.…”

Section: Introductionmentioning

confidence: 99%

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Preparation of biocompatible and photostable PEGylated red fluorescent nanoparticles for cellular imaging

et al. 2015

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PEGylated red fluorescent nanoparticles with excellent biocompatibility and photostablity were facilely prepared from nonluminous materials: first red fluorescent nanoparticles (GCC NPs) were robustly prepared from chitosan and glutaraldehyde; then the amino groups and hydroxyl groups on GCC NPs surface were modified with 2-bromoisobutyryl bromide to get the GCC-Br, which was employed as the nanoparticles initiator in ATRP system to finally obtain the GCC-poly(PEGMA) conjugates. The resulted GCC-poly(PEGMA) can emit biofavorable deep red luminescence, which was quite stable and anti-photobleaching. Furthermore, GCC-poly(PEGMA) demonstrated excellent biocompatibility and water dispersibility due to the PEGMA chains conjugated on the surface; and the abundant hydroxyl groups on the surface can be further functionalized with diverse other groups or large biomolecules. This construction method demonstrated huge superiorities in its simple strategy and economic value, and their successful cellular imaging applications made them highly potential for various biomedical applications. Abstract Biocompatible and photostable PEGylated red fluorescent nanoparticles were prepared via surface-initiated ATRP and their cellular imaging application was successfully demonstrated.

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supporting

confidence: 90%

Section: Cellular Imaging Of Gcc-poly(pegma)mentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Preparation of biocompatible and photostable PEGylated red fluorescent nanoparticles for cellular imaging

et al. 2015

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“…It combined the proton sponge-mediated endo -lysosomal escape ability and dual targeting (flate and trastuzumab) had minimal cardiotoxicity, hepatotoxicity, and nephrotoxicity along with its high therapeutic efficacy. 312 Sun et al 313 reported two DOX functionalized prodrugs, one that was acid-sensitive ( cis -aconitic anhydride conjugated to PEG (CAD–PEG–CAD)) and the other was insensitive to pH changes (succinic anhydride conjugated to PEG (SAD–PEG–SAD)) which both self-assembled into micelles. Both micelles were stable at physiological pH ( i.e.…”

Section: Different Stimuli-responsive Mnpsmentioning

confidence: 99%

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

et al. 2016

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New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive “smart” MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.

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“…The day, on which treatment was begun, designated as a day zero and study was terminated on 21st day; tumor volume and weight of animal was measured alternatively. At the end of study, blood and vital body organs were collected and subjected to blood count, biomarkers analysis and histopathological examinations (Negi et al, 2014;Lale et al, 2015).…”

Section: In Vivo Antitumor Efficacy and Toxicological Studiesmentioning

confidence: 99%

Improved oral efficacy of epirubicin through polymeric nanoparticles: pharmacodynamic and toxicological investigations

et al. 2016

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Epirubicin (EPI) elicits poor-oral bioavailability hence commercially available as injection for intravenous administration which follows a rapid increase and fast decay in plasma drug concentration often needs a frequent dosing that may lead to serious side effects. Aim of the present study is to develop a nanoparticulate system which could deliver epirubicin effectively via oral administration and could eventually promote new concept ''chemotherapy at home.'' In this perspective, epirubicin loaded Poly-lactide-co-glycolic acid nanoparticles (EPI-NPs) were developed by double emulsion evaporation techniques and evaluated for its safety and efficacy against Ehrlich's Ascites (EAT) induced tumor in balb/c mice. In vivo fate of nanoparticles after oral administration in Albino wistar rats was also studied. EPI-NPs showed marked reduction in tumor size $40% while tumor size was increased 3.55 and 3.28 folds in control as well as in group treated orally with free epirubicin solution (EPI-S), respectively. Furthermore, toxicological evaluation demonstrated insignificant difference in levels of biomarkers including MDA, CAT, SOD, LDH, CK-MB, AST and ALT when EPI-NPs-oral treatment was compared with control group while levels of these biomarkers were found extremely significant in group treated with EPI-S (i.v). and demonstrated increment in LDH (p50.001), CK-MB (p50.001), AST (p50.001), ALT (p50.001) and MDA levels (p50.001) and reduction in SOD (p50.001) and CAT levels (p50.001) thus confirmed better safety profile of EPI-NPs oral than EPI-S i.v. Biodistribution study demonstrated the presence of NPs in different body organs and blood which suggests probability of NPs translocation across intestine thus at the tumor site.

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Multifunctional ATRP based pH responsive polymeric nanoparticles for improved doxorubicin chemotherapy in breast cancer by proton sponge effect/endo-lysosomal escape

Abstract: Folic acid and trastuzumab functionalized pH responsive polymeric nanoparticles for intracellular doxorubicin delivery in breast cancer.

Cited by 53 publications

References 56 publications

Preparation of biocompatible and photostable PEGylated red fluorescent nanoparticles for cellular imaging

Preparation of biocompatible and photostable PEGylated red fluorescent nanoparticles for cellular imaging

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

Improved oral efficacy of epirubicin through polymeric nanoparticles: pharmacodynamic and toxicological investigations

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