Targeting nano drug delivery to cancer cells using tunable, multi‐layer, silver‐decorated gold nanorods

Nima, Zeid A.; Alwbari, Ahmed; Dantuluri, Vijayalakshmi; Hamzah, Rabab N.; Sra, Natasha; Motwani, Pooja; Arnaoutakis, Konstantinos; Levy, Rebecca; Bohliqa, Amani F.; Nedosekin, Dmitry A.; Zharov, Vladimir P.; Makhoul, Issam; Biris, Alexandru S.

doi:10.1002/jat.3495

Cited by 35 publications

(28 citation statements)

References 43 publications

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“…with an aspect ratio of length/diameter: ~3) were synthesized using a previously reported seed-mediated method 45,49 . Performance, toxicity, and interaction of these AuNRs, functionalized with various substances, with cancer cells have already been analyzed in our previous studies 47,48 . In this work, fluorescent nano-agents (nanorod conjugates) were prepared according to the EDC/NHS coupling reaction using both carboxylic (from HS-PEG-COOH) and amine (from BODIPY-TR-NH 2 ) functional groups in a one-step approach (Fig.…”

Section: Synthesis and Characterization Of Nanoparticle Conjugates Gmentioning

confidence: 99%

“…Nanoparticle interaction observed via fluorescence and PA analysis. Performance, toxicity, and interaction of gold nanorods with various functionalizations with cancer cells have been investigated previously 47,48 . In this study, we used a 50-μg/mL concentration of conjugated nanoparticles for all the spheroid studies because it allows excellent imaging and no toxicity has been detected at that concentration.…”

Section: Synthesis and Characterization Of Nanoparticle Conjugates Gmentioning

confidence: 99%

“…AuNRs were prepared using previous reported protocols 45,47,49 . First, AuNRs (1 batch of ~1,000 µg) were prepared from a seed solution.…”

Section: Aunr Synthesis and Conjugation With Nh 2 -Tr-bdp Fluorescentmentioning

confidence: 99%

“…Previously, we successfully used gold nanoparticles' unique photoacoustic (PA) and photothermal (PT) signatures to study their theragnostic behavior and mechanisms of interactions with cells in 2D culture and in vivo cancer and immune system models [43][44][45][46][47][48] . Herein, we have developed an avascular 3D pancreatic microtumor model by varying the ratio of Panc-1/PSCs.…”

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Tracking Gold Nanorods’ Interaction with Large 3D Pancreatic-Stromal Tumor Spheroids by Multimodal Imaging: Fluorescence, Photoacoustic, and Photothermal Microscopies

Darrigues

Nima

Nedosekin

et al. 2020

Sci Rep

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pancreatic cancer is one of the most complex types of cancers to detect, diagnose, and treat. However, the field of nanomedicine has strong potential to address such challenges. When evaluating the diffusion and penetration of theranostic nanoparticles, the extracellular matrix (ECM) is of crucial importance because it acts as a barrier to the tumor microenvironment. in the present study, the penetration of functionalized, fluorescent gold nanorods into large (>500 μm) multicellular 3D tissue spheroids was studied using a multimodal imaging approach. the spheroids were generated by coculturing pancreatic cancer cells and pancreatic stellate cells in multiple ratios to mimic variable tumor-stromal compositions and to investigate nanoparticle penetration. fluorescence live imaging, photothermal, and photoacoustic analysis were utilized to examine nanoparticle behavior in the spheroids. Uniquely, the nanorods are intrinsically photoacoustic and photothermal, enabling multiimaging detection even when fluorescence tracking is not possible or ideal. Nanomedicine for cancer treatments-the use of nanosized structures in cancer therapeutics and/or imaginghas been heavily investigated over the last two decades 1. Nano-sized delivery systems are useful theragnostic agents for enhanced tumor penetration, accumulation, and targeting potency. Studies of nanoparticle (NP)-based therapies have mainly focused on targeted cancer cell treatment but also include cancer stem cells 2 , stromal cancer microenvironment 3-5 , and/or cellular immune system 6,7. As a physical barrier that limits NP penetration and distribution, the extracellular matrix (ECM) is a crucial concern when evaluating the effects of nanoscale cancer therapies. Recent work showed that the ECM can be regulated by using gold NPs to interrupt the crosstalk between cancer cells and stellate cells, which reeducates the stellate cells 8,9. However, the development of nanosystems for cancer treatment has been hampered by the limitations of current in vitro models, which are generally based on two-dimensional (2D) cell cultures. These 2D models struggle to provide an accurate representation of the in vivo environment and its components, which include the dynamic tumor microenvironment (TME), cell heterogeneity, and nutrient and pH gradient interaction between cells and the ECM 10. The real TME is composed not only of cancer cells but also of others cells such as fibroblasts, cancer-associated fibroblasts (CAFs), stromal cells, myofibroblasts, endothelial cells, adipocytes, various immune cells, and extra-abundant compromised ECM. These heterocellular components can induce adaptive survival mechanisms of cancer such as treatment resistance, a leading cause of cancer-related mortality and one of the greatest challenges in cancer treatment 11. The cellular responses and cell signaling that take place in the TME often cannot be mimicked in a 2D in vitro model.

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Section: Synthesis and Characterization Of Nanoparticle Conjugates Gmentioning

confidence: 99%

Section: Synthesis and Characterization Of Nanoparticle Conjugates Gmentioning

confidence: 99%

“…AuNRs were prepared using previous reported protocols 45,47,49 . First, AuNRs (1 batch of ~1,000 µg) were prepared from a seed solution.…”

Section: Aunr Synthesis and Conjugation With Nh 2 -Tr-bdp Fluorescentmentioning

confidence: 99%

mentioning

confidence: 99%

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Tracking Gold Nanorods’ Interaction with Large 3D Pancreatic-Stromal Tumor Spheroids by Multimodal Imaging: Fluorescence, Photoacoustic, and Photothermal Microscopies

Darrigues

Nima

Nedosekin

et al. 2020

Sci Rep

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“…15 Among various photothermal nanomaterials, gold nanorods (GNRs) is an ideal phototherapeutic agent for PTT because of their tunable longitudinal surface plasmon resonance (LSPR) peak at the rst NIR (NIR-I) (650-950 nm) to match NIR resources with different wavelengths. [16][17][18][19][20][21][22][23][24][25][26][27] The low drug loading capability and difficult surface modication of naked GNRs limit their further application in targeted drug delivery. [28][29][30] Mesoporous silica coating have been successfully applied in targeted drug delivery and tumor therapy due to its uniform and tunable particle/pore sizes, high surface area and pore volume, facile surface functionalization as well as favorable biocompatibility.…”

Section: Introductionmentioning

confidence: 99%