Enhanced toxicity and cellular uptake of methotrexate-conjugated nanoparticles in folate receptor-positive cancer cells by decorating with folic acid-conjugated d -α-tocopheryl polyethylene glycol 1000 succinate

Junyaprasert, Varaporn Buraphacheep; Dhanahiranpruk, Sirithip; Suksiriworapong, Jiraphong; Sripha, Kittisak; Moongkarndi, Primchanien

doi:10.1016/j.colsurfb.2015.09.013

Cited by 20 publications

(9 citation statements)

References 39 publications

(48 reference statements)

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“…Previously, we have shown that BCNs (non-MNS-loaded) are taken up into endolysosomes of cells following phagocytosis by RAW 264.7 macrophages. Here, we have observed similar uptake of MBCNs by MCF7 cells, which have been shown to be phagocytic and to uptake nanoparticles between 250 and 375 nm via phagocytosis or macropinocytosis. − On confocal microscopy, punctae of both DiD (red) and FITC-BSA (green) signal were colocalized with lysosomal dye LysoTracker (blue) signal (Figure a). In addition, flow cytometric analysis showed a positive correlation for FITC-BSA and DiD cell uptake, indicating successful codelivery of the small-molecule payloads (Figure b, background cell fluorescence data in Figure S6).…”

Section: Resultssupporting

confidence: 53%

Magnetic Nanostructure-Loaded Bicontinuous Nanospheres Support Multicargo Intracellular Delivery and Oxidation-Responsive Morphological Transitions

Modak

Bobbala

Lescott

et al. 2020

ACS Appl. Mater. Interfaces

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Magnetic nanostructures (MNS) have a wide range of biological applications due to their biocompatibility, superparamagnetic properties, and customizable composition that includes iron oxide (Fe3O4), Zn2+, and Mn2+. However, several challenges to the biomedical usage of MNS must still be addressed, such as formulation stability, inability to encapsulate therapeutic payloads, and variable clearance rates in vivo. Here, we enhance the utility of MNS during controlled delivery applications via encapsulation within polymeric bicontinuous nanospheres (BCNs) composed of poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-b-PPS) copolymers. PEG-b-PPS BCNs have demonstrated versatile encapsulation and delivery capabilities for both hydrophilic and hydrophobic payloads due to their unique and highly organized cubic phase nanoarchitecture. MNS-embedded BCNs (MBCNs) were thus coloaded with physicochemically diverse molecular payloads using the technique of flash nanoprecipitation and characterized in terms of their structure and in vivo biodistribution following intravenous administration. Retention of the internal aqueous channels and cubic architecture of MBCNs were verified using cryogenic transmission electron microscopy and small-angle X-ray scattering, respectively. MBCNs demonstrated improvement in magnetic resonance imaging (MRI) contrast enhancement (r 2 relaxivity) as compared to free MNS, which in combination with scanning transmission electron microscopy and energy-dispersive X-ray spectroscopy evidenced the clustering and continued access to water of MNS following encapsulation. Furthermore, MBCNs were found to be noncytotoxic and able to deliver their hydrophilic and hydrophobic small-molecule payloads both in vitro and in vivo. Finally, the oxidation sensitivity of the hydrophobic PPS block allowed MBCNs to undergo a unique, triggerable transition in morphology into MNS-bearing micellar nanocarriers. In summary, MBCNs are an attractive platform for the delivery of molecular and nanoscale payloads for diverse on-demand and sustained drug delivery applications.

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Section: Resultssupporting

confidence: 53%

Magnetic Nanostructure-Loaded Bicontinuous Nanospheres Support Multicargo Intracellular Delivery and Oxidation-Responsive Morphological Transitions

Modak

Bobbala

Lescott

et al. 2020

ACS Appl. Mater. Interfaces

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“…Dulbecco’s modified Eagle’s medium (DMEM) and basic RPMI1640 medium were commercially available from Thermo Fisher (Shanghai, China). Alkynyl-modified Gal, TPGS-N 3 , BNN, and RBSP (rhodamine B spirolactam-based probe) were prepared based on the reported methods.…”

Section: Methodsmentioning

confidence: 99%

TPGS–Galactose-Modified Polydopamine Co-delivery Nanoparticles of Nitric Oxide Donor and Doxorubicin for Targeted Chemo–Photothermal Therapy against Drug-Resistant Hepatocellular Carcinoma

Mao

Zhang

et al. 2021

ACS Appl. Mater. Interfaces

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The lack of cancer cell specificity and the occurrence of multidrug resistance (MDR) are two major obstacles in the treatment of hepatocellular carcinoma (HCC). To tackle these challenges, a novel nanoparticle (NP)-based drug delivery system (DDS) with a core/shell structure consisted of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)–galactose (Gal)/polydopamine (PDA) is fabricated. The NP is loaded with doxorubicin (DOX) and a nitric oxide (NO) donor N,N′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine (BNN) sensitive to heat to afford NO-DOX@PDA-TPGS-Gal. The unique binding of Gal to asialoglycoprotein receptor (ASGPR) and the pH-sensitive degradation of NP ensure the targeted transportation of NP into liver cells and the release of DOX in HCC cells. The near-infrared (NIR) light further facilitates DOX release and initiates NO generation from BNN due to the photothermal property of PDA. In addition to the cytotoxicity contributed by DOX, NO, and heat, TPGS and NO act as MDR reversal agents to inhibit P-glycoprotein (P-gp)-related efflux of DOX by HepG2/ADR cells. The combined chemo–photothermal therapy (chemo-PTT) by NO-DOX@PDA-TPGS-Gal thus shows potent anti-cancer activity against drug-resistant HCC cells in vitro and in vivo and significantly prolongs the life span of drug-resistant tumor-bearing mice. The present work provides a useful strategy for highly targeted and MDR reversal treatment of HCC.

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“…Such an effect was reported in some previous studies [ 36 , 37 ]. Several studies have shown that MTX is able to bind and target FRs [ 38 , 39 ]. Depending on this ability, we decided to use MTX as therapeutic and ligand moiety to modify the G4 dendrimer for targeting FR expressing cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Silencing of HMGA2 by siRNA Loaded Methotrexate Functionalized Polyamidoamine Dendrimer for Human Breast Cancer Cell Therapy

Gaballu

Cho

Dehghan

et al. 2021

Genes

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The transcription factor high mobility group protein A2 (HMGA2) plays an important role in the pathogenesis of some cancers including breast cancer. Polyamidoamine dendrimer generation 4 is a kind of highly branched polymeric nanoparticle with surface charge and highest density peripheral groups that allow ligands or therapeutic agents to attach it, thereby facilitating target delivery. Here, methotrexate (MTX)- modified polyamidoamine dendrimer generation 4 (G4) (G4/MTX) was generated to deliver specific small interface RNA (siRNA) for suppressing HMGA2 expression and the consequent effects on folate receptor (FR) expressing human breast cancer cell lines (MCF-7, MDA-MB-231). We observed that HMGA2 siRNA was electrostatically adsorbed on the surface of the G4/MTX nanocarrier for constructing a G4/MTX-siRNA nano-complex which was verified by changing the final particle size and zeta potential. The release of MTX and siRNA from synthesized nanocomplexes was found in a time- and pH-dependent manner. We know that MTX targets FR. Interestingly, G4/MTX-siRNA demonstrates significant cellular internalization and gene silencing efficacy when compared to the control. Besides, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay demonstrated selective cell cytotoxicity depending on the folate receptor expressing in a dose-dependent manner. The gene silencing and protein downregulation of HMGA2 by G4/MTX-siRNA was observed and could significantly induce cell apoptosis in MCF-7 and MDA-MB-231 cancer cells compared to the control group. Based on the findings, we suggest that the newly developed G4/MTX-siRNA nano-complex may be a promising strategy to increase apoptosis induction through HMGA2 suppression as a therapeutic target in human breast cancer.

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Enhanced toxicity and cellular uptake of methotrexate-conjugated nanoparticles in folate receptor-positive cancer cells by decorating with folic acid-conjugated d -α-tocopheryl polyethylene glycol 1000 succinate

Cited by 20 publications

References 39 publications

Magnetic Nanostructure-Loaded Bicontinuous Nanospheres Support Multicargo Intracellular Delivery and Oxidation-Responsive Morphological Transitions

Magnetic Nanostructure-Loaded Bicontinuous Nanospheres Support Multicargo Intracellular Delivery and Oxidation-Responsive Morphological Transitions

TPGS–Galactose-Modified Polydopamine Co-delivery Nanoparticles of Nitric Oxide Donor and Doxorubicin for Targeted Chemo–Photothermal Therapy against Drug-Resistant Hepatocellular Carcinoma

Silencing of HMGA2 by siRNA Loaded Methotrexate Functionalized Polyamidoamine Dendrimer for Human Breast Cancer Cell Therapy

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