Neuroendocrine Tumor‐Targeted Upconversion Nanoparticle‐Based Micelles for Simultaneous NIR‐Controlled Combination Chemotherapy and Photodynamic Therapy, and Fluorescence Imaging

Chen, Guojun; Jaskula-Sztul, Renata; Esquibel, Corinne R.; Lou, Irene; Zheng, Qifeng; Dammalapati, Ajitha; Harrison, April D.; Eliceiri, Kevin W.; Tang, Weiping; Chen, Herbert; Gong, Shaoqin

doi:10.1002/adfm.201604671

Cited by 145 publications

(115 citation statements)

References 80 publications

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“…We and others have previously demonstrated that a rapid release of anticancer drugs within the tumor sites can lead to superior anticancer efficacies. 32–35 In this work, the temperature elevation generated by the CuS NP core under NIR light induced both the PTT effect and the hydrophobic-to-hydrophilic phase transition of PAAmAN, leading to a rapid drug release, thereby achieving NIR-controlled combination chemotherapy and PTT. We tested these CuS-based micelles in triple-negative breast cancer (TNBC) models.…”

Section: Introductionmentioning

confidence: 82%

CuS-Based Theranostic Micelles for NIR-Controlled Combination Chemotherapy and Photothermal Therapy and Photoacoustic Imaging

Chen¹,

Wang³

et al. 2017

ACS Appl. Mater. Interfaces

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Cancer remains a major threat to human health due to low therapeutic efficacies of currently available cancer treatment options. Nanotheranostics, capable of simultaneous therapy and diagnosis/monitoring of diseases, has attracted increasing amounts of attention, particularly for cancer treatment. In this study, CuS-based theranostic micelles capable of simultaneous combination chemotherapy and photothermal therapy (PTT), as well as photoacoustic imaging, were developed for targeted cancer therapy. The micelle was formed by a CuS nanoparticle (NP) functionalized by thermosensitive amphiphilic poly(acrylamide-acrylonitrile)–poly(ethylene glycol) block copolymers. CuS NPs under near-infrared (NIR) irradiation induced a significant temperature elevation, thereby enabling NIR-triggered PTT. Moreover, the hydrophobic core formed by poly(acrylamide-acrylonitrile) segments used for drug encapsulation exhibited an upper critical solution temperature (UCST; ~38 °C), which underwent a hydrophobic-to-hydrophilic transition once the temperature rose above the UCST induced by NIR-irradiated CuS NPs, thereby triggering a rapid drug release and enabling NIR-controlled chemotherapy. The CuS-based micelles conjugated with GE11 peptides were tested in an epidermal growth factor receptor-overexpressing triple-negative breast cancer model. In both two-dimensional monolayer cell and three-dimensional multicellular tumor spheroid models, GE11-tagged CuS-based micelles under NIR irradiation, enabling the combination chemotherapy and PTT, exhibited the best therapeutic outcome due to a synergistic effect. These CuS-based micelles also displayed a good photoacoustic imaging ability under NIR illumination. Taken together, this multifunctional CuS-based micelle could be a promising nanoplatform for targeted cancer nanotheranostics.

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Section: Introductionmentioning

confidence: 82%

CuS-Based Theranostic Micelles for NIR-Controlled Combination Chemotherapy and Photothermal Therapy and Photoacoustic Imaging

Chen¹,

Wang³

et al. 2017

ACS Appl. Mater. Interfaces

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“…Amine-functionalized NaYF 4 :Yb/Tm/Er UCNPs (NH 2 -UCNPs) were prepared using a thermal decomposition method following the same protocol we previously reported [30], which was then converted to β-CD functionalized UCNPs (CD-UCNPs) through amidization. The average size of the CD-UCNPs determined by transmission electron microscopy (TEM) was 15 nm in diameter (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The amine-functionalized UCNPs (NH 2 -UCNPs) were first prepared following the same protocol using a thermal decomposition method as published previously [30]. CD-UCNPs were then synthesized through amidization between NH 2 -UCNP and carboxymethyl-β-cyclodextrin.…”

Section: Methodsmentioning

confidence: 99%

“…siRNAs tagged with azobenzene (Azo-siRNAs) were complexed onto the NaYF 4 :Yb/Tm/Er UCNPs functionalized with β-cyclodextrin (CD) through a host–guest interaction. The NIR-activated UCNP core can emit UV light [30], which can effectively photoisomerize azobenzene from the trans - to cis -state, thus releasing siRNAs due to the unmatched host–guest pairs (Fig. 1(A)).…”

Section: Introductionmentioning

confidence: 99%

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NIR-induced spatiotemporally controlled gene silencing by upconversion nanoparticle-based siRNA nanocarrier

Chen

Xie

et al. 2018

Journal of Controlled Release

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Spatiotemporal control over the release or activation of biomacromolecules such as siRNA remains a significant challenge. Light-controlled release has gained popularity in recent years; however, a major limitation is that most photoactivable compounds/systems respond only to UV irradiation, but not near-infrared (NIR) light that offers a deeper tissue penetration depth and better biocompatibility. This paper reports a simple NIR-to-UV upconversion nanoparticle (UCNP)-based siRNA nanocarrier for NIR-controlled gene silencing. siRNA is complexed onto a NaYF4:Yb/Tm/Er UCNP through an azobenzene (Azo)–cyclodextrin (CD) host–guest interaction. The UV emission generated by the NIR-activated UCNP effectively triggers the trans-to-cis photoisomerization of azobenzene, thus leading to the release of siRNA due to unmatched host – guest pairs. The UCNP-siRNA complexes are also functionalized with PEG (i.e., UCNP-(CD/Azo)-siRNA/PEG NPs), targeting ligands (i.e., EGFR-specific GE11 peptide), acid-activatable cell-penetrating peptides (i.e., TH peptide), and imaging probes (i.e., Cy5 fluorophore). The UCNP-(CD/Azo)-siRNA/PEG NPs with both GE11 and TH peptides display a high level of cellular uptake and an excellent endosomal/lysosomal escape capability. More importantly, NIR-controlled spatiotemporal knockdown of GFP expression is successfully achieved in both a 2D monolayer cell model and a 3D multicellular tumor spheroid model. Thus, this simple and versatile nanoplatform has great potential for the selective activation or release of various biomacromolecules.

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“…NPs can greatly enhance the stability and cellular uptake of the siRNA molecules [15,16]. Furthermore, NPs are attractive for targeted cancer therapy due to their passive (attributed to the enhanced permeability and retention (EPR) effect) and active (via specific ligand conjugation) tumor-targeting abilities [17,18]. However, in order to achieve high gene silencing efficiency, once the NPs are taken up by the target cancer cells, efficient siRNA escape from the acidic endosome/lysosome compartments and efficient siRNA decomplexation from its carrier in the cytosol are essential [6,19–22].…”

Section: Introductionmentioning

confidence: 99%

Tumor-targeted pH/redox dual-sensitive unimolecular nanoparticles for efficient siRNA delivery

Chen

Wang

Xie

et al. 2017

Journal of Controlled Release

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A unique pH/redox dual-sensitive cationic unimolecular nanoparticle (NP) enabling excellent endosomal/lysosomal escape and efficient siRNA decomplexation inside the target cells was developed for tumor-targeted delivery of siRNA. siRNA was complexed into the cationic core of the unimolecular NP through electrostatic interactions. The cationic core used for complexing siRNA contained reducible disulfide bonds that underwent intracellular reduction owing to the presence of high concentrations of reduced glutathione (GSH) inside the cells, thereby facilitating the decomplexation of siRNA from the unimolecular NPs. The cationic polymers were conjugated onto the hyperbranched core (H40) via a pH-sensitive bond, which further facilitated the decomplexation of siRNA from the NPs. In vitro studies on the siRNA release behaviors showed that dual stimuli (pH = 5.3, 10 mM GSH) induced the quickest release of siRNA from the NPs. In addition, the imidazole groups attached to the cationic polymer segments enhanced the endosomal/lysosomal escape of NPs via the proton sponge effect. Intracellular tracking studies revealed that siRNA delivered by unimolecular NPs was efficiently released to the cytosol. Moreover, the GE11 peptide, an anti-EGFR peptide, enhanced the cellular uptake of NPs in MDA-MB-468, an EFGR-overexpressing triple negative breast cancer (TNBC) cell line. The GE11-conjugated, GFP-siRNA-complexed NPs exhibited excellent GFP gene silencing efficiency in GFP-MDA-MB-468 TNBC cells without any significant cytotoxicity. Therefore, these studies suggest that this smart unimolecular NP could be a promising nanoplatform for targeted siRNA delivery to EFGR-overexpressing cancer cells.

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Neuroendocrine Tumor‐Targeted Upconversion Nanoparticle‐Based Micelles for Simultaneous NIR‐Controlled Combination Chemotherapy and Photodynamic Therapy, and Fluorescence Imaging

Cited by 145 publications

References 80 publications

CuS-Based Theranostic Micelles for NIR-Controlled Combination Chemotherapy and Photothermal Therapy and Photoacoustic Imaging

CuS-Based Theranostic Micelles for NIR-Controlled Combination Chemotherapy and Photothermal Therapy and Photoacoustic Imaging

NIR-induced spatiotemporally controlled gene silencing by upconversion nanoparticle-based siRNA nanocarrier

Tumor-targeted pH/redox dual-sensitive unimolecular nanoparticles for efficient siRNA delivery

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