A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self‐Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA‐MB‐231 Human Breast Cancer Cells

Viswanathan, Geetha; Hsu, Yu-Hsuan; Voon, Siew Hui; Imae, Toyoko; Siriviriyanun, Ampornphan; Lee, Hong Boon; Kiew, Lik Voon; Chung, Lip Yong; Yusa, Shin‐ichi

doi:10.1002/mabi.201500435

Cited by 14 publications

(4 citation statements)

References 51 publications

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“…30 In plasma at pH 7.4, both S@C-PLGA NPs and S@PLGA NPs exhibited similar drug release patterns, where ~12% of Stattic was released rapidly within 2 h. This indicated rapid diffusion of Stattic from the polymeric matrix to the plasma protein, likely owing to affinity of Stattic towards albumin molecules. 31 A similar observation has been reported previously, where Stattic entrapped within a synthetic polymeric micellar carrier (P71D3) 32 was rapidly released when the drug-carriercomplexes were incubated in an albumin solution. 33 The Stattic burst release from S@C-PLGA NPs in this study was considerably low (< 15%), suggesting the suitability of C-PLGA NPs as the delivery vehicles for Stattic and antimetastatic drugs with a similar chemical structure.…”

Section: Stattic Releasing Profile In Pbs and Plasmasupporting

confidence: 83%

Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic – A STAT3 Dimerization Blocker

Fong¹,

Foo²,

Saw³

et al. 2022

IJN

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The use of nanocarriers to improve the delivery and efficacy of antimetastatic agents is less explored when compared to cytotoxic agents. This study reports the entrapment of an antimetastatic Signal Transducer and Activator of Transcription 3 (STAT3) dimerization blocker, Stattic (S) into a chitosan-coated-poly(lactic-co-glycolic acid) (C-PLGA) nanocarrier and the improvement on the drug's physicochemical, in vitro and in vivo antimetastatic properties post entrapment. Methods: In vitro, physicochemical properties of the Stattic-entrapped C-PLGA nanoparticles (S@C-PLGA) and Stattic-entrapped PLGA nanoparticles (S@PLGA, control) in terms of size, zeta potential, polydispersity index, drug loading, entrapment efficiency, Stattic release in different medium and cytotoxicity were firstly evaluated. The in vitro antimigration properties of the nanoparticles on breast cancer cell lines were then studied by Scratch assay and Transwell assay. Study on the in vivo antitumor efficacy and antimetastatic properties of

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Section: Stattic Releasing Profile In Pbs and Plasmasupporting

confidence: 83%

Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic – A STAT3 Dimerization Blocker

Fong¹,

Foo²,

Saw³

et al. 2022

IJN

Self Cite

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“…This observation is supported by another study wherein enhanced uptake of DOX was observed when loaded in dextran and poly(D,L-lactide- co -glycolide) blocks copolymer polymeric micelles as compared to DOX alone in DOX-resistant human cholangiocarcinoma (HuCC-T1) cells (51). Viswanathan et al observed twofold enhancement in the DOX potency in MDA-MB-231 cells when loaded in di-block copolymer-based micelles (52). …”

Section: Discussionmentioning

confidence: 99%

Cholecalciferol-PEG Conjugate Based Nanomicelles of Doxorubicin for Treatment of Triple-Negative Breast Cancer

et al. 2017

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Triple-negative breast cancer (TNBC) is the leading cancer in women. Chemotherapeutic agents used for TNBC are mainly associated with dose-dependent toxicities and development of resistance. Hence, novel strategies to overcome resistance and to offer dose reduction are warranted. In this study, we designed a novel dual-functioning agent, conjugate of cholecalciferol with PEG2000 (PEGCCF) which can self-assemble into micelles to encapsulate doxorubicin (DOX) and act as a chemosensitizer to improve the therapeutic potential of DOX. DOX-loaded PEGCCF (PEGCCF-DOX) micelles have particle size, polydispersity index (PDI), and zeta potential of 40 ± 8.7 nm, 0.180 ± 0.051, and 2.39 ± 0.157 mV, respectively. Cellular accumulation studies confirmed that PEGCCF was able to concentration-dependently enhance the cellular accumulation of DOX and rhodamine 123 in MDA-MB-231 cells through its P-glycoprotein (P-gp) inhibition activity. PEGCCF-DOX exhibited 1.8-, 1.5-, and 2.9-fold enhancement in cytotoxicity of DOX in MDA-MB-231, MDA-MB-468, and MDA-MB-231DR (DOX-resistant) cell lines, respectively. Western blot analyses showed that PEGCCF-DOX caused significant reduction in tumor markers including mTOR, c-Myc, and antiapoptotic marker Bcl-xl along with upregulation of preapoptotic marker Bax. Further, reduction in mTOR activity by PEGCCF-DOX indicates reduced P-gp activity due to P-gp downregulation as well and, hence, PEGCCF causes enhanced chemosensitization and induces apoptosis. Substantially enhanced apoptotic activity of DOX (10-fold) in MDA-MB-231(DR) cells confirmed apoptotic potential of PEGCCF. Conclusively, PEGCCF nanomicelles are promising delivery systems for improving anticancer activity of DOX in TNBC, thereby reducing its side effects and may act as a potential carrier for other chemotherapeutic agents.

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“…The hydrophobic core of a micelle can sequester a high dose of a particular drug while also having slow release, meaning less frequent injections. Because of their high density of well-structured hydrophobic groups, the use of dendrons such as poly(benzyl ether) in the core of a block copolymer micelle increases the loading capacity of doxorubicin (DOX) to nearly twice that of similar linear copolymer vesicles and increases DOX delivery to tumors in mice by 2–5-fold compared to free DOX . The same drug has also been loaded into micelles generated from more rapidly biodegradable PCL dendron–PEG block copolymers with an 18% higher loading capacity and a drug release time 45 days longer than similar linear block copolymers .…”

Section: Dendron Micelles In Cancer Drug Loading Transport Targeting ...mentioning

confidence: 99%

Dendritic–Linear Copolymer and Dendron Lipid Nanoparticles for Drug and Gene Delivery

et al. 2022

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Polymers constitute a diverse class of macromolecules that have demonstrated their unique advantages to be utilized for drug or gene delivery applications. In particular, polymers with a highly ordered, hyperbranched structure“dendrons”offer significant benefits to the design of such nanomedicines. The incorporation of dendrons into block copolymer micelles can endow various unique properties that are not typically observed from linear polymer counterparts. Specifically, the dendritic structure induces the conical shape of unimers that form micelles, thereby improving the thermodynamic stability and achieving a low critical micelle concentration (CMC). Furthermore, through a high density of highly ordered functional groups, dendrons can enhance gene complexation, drug loading, and stimuli-responsive behavior. In addition, outward-branching dendrons can support a high density of nonfouling polymers, such as poly(ethylene glycol), for serum stability and variable densities of multifunctional groups for multivalent cellular targeting and interactions. In this paper, we review the design considerations for dendron–lipid nanoparticles and dendron micelles formed from amphiphilic block copolymers intended for gene transfection and cancer drug delivery applications. These technologies are early in preclinical development and, as with other nanomedicines, face many obstacles on the way to clinical adoption. Nevertheless, the utility of dendron micelles for drug delivery remains relatively underexplored, and we believe there are significant and dramatic advancements to be made in tumor targeting with these platforms.

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A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self‐Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA‐MB‐231 Human Breast Cancer Cells

Cited by 14 publications

References 51 publications

Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic – A STAT3 Dimerization Blocker

Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic – A STAT3 Dimerization Blocker

Cholecalciferol-PEG Conjugate Based Nanomicelles of Doxorubicin for Treatment of Triple-Negative Breast Cancer

Dendritic–Linear Copolymer and Dendron Lipid Nanoparticles for Drug and Gene Delivery

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