Assembly of Aptamer Switch Probes and Photosensitizer on Gold Nanorods for Targeted Photothermal and Photodynamic Cancer Therapy

Wang, Jian; Zhu, Guizhi; You, Mingxu; Song, Erqun; Shukoor, Mohammed Ibrahim; Zhang, Kejing; Altman, Meghan O.; Chen, Yan; Zhu, Zhi; Huang, Cheng; Tan, Weihong

doi:10.1021/nn300694v

Cited by 344 publications

(283 citation statements)

References 38 publications

(95 reference statements)

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“…Thus, we hypothesized that the use of AuNRs allows us to apply near-infrared (NIR) laser to generate heat efficiently through nonradiative processes (13,30,31). AuNRs, due to their unique chemical, physical, and optical properties, have been used in drug delivery (32), bioimaging, and PPTT of cancer (33)(34)(35)(36). NIR light is a low energetic (safe) light that can deeply penetrate the tissues, which could potentially enhance the AuNRs' effects on cytoskeletal proteins and inhibit migration.…”

Section: Significancementioning

confidence: 99%

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Ali

Tang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

164

113

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Metastasis is responsible for most cancer-related deaths, but the current clinical treatments are not effective. Recently, gold nanoparticles (AuNPs) were discovered to inhibit cancer cell migration and prevent metastasis. Rationally designed AuNPs could greatly benefit their antimigration property, but the molecular mechanisms need to be explored. Cytoskeletons are cell structural proteins that closely relate to migration, and surface receptor integrins play critical roles in controlling the organization of cytoskeletons. Herein, we developed a strategy to inhibit cancer cell migration by targeting integrins, using Arg-Gly-Asp (RGD) peptide-functionalized gold nanorods. To enhance the effect, AuNRs were further activated with 808-nm near-infrared (NIR) light to generate heat for photothermal therapy (PPTT), where the temperature was adjusted not to affect the cell viability/proliferation. Our results demonstrate changes in cell morphology, observed as cytoskeleton protrusions-i.e., lamellipodia and filopodia-were reduced after treatment. The Western blot analysis indicates the downstream effectors of integrin were attracted toward the antimigration direction. Proteomics results indicated broad perturbations in four signaling pathways, Rho GTPases, actin, microtubule, and kinases-related pathways, which are the downstream regulators of integrins. Due to the dominant role of integrins in controlling cytoskeleton, focal adhesion, actomyosin contraction, and actin and microtubule assembly have been disrupted by targeting integrins. PPTT further enhanced the remodeling of cytoskeletal proteins and decreased migration. In summary, the ability of targeting AuNRs to cancer cell integrins and the introduction of PPTT stimulated broad regulation on the cytoskeleton, which provides the evidence for a potential medical application for controlling cancer metastasis.gold nanorods | cytoskeleton | integrin | metastasis | plasmonic photothermal therapy

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Section: Significancementioning

confidence: 99%

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Ali

Tang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

164

113

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“…At an irradiation power density of 5 mW/cm 2 , the temperature of PheoA-HA/AuNPs solution reached a final temperature of approximately 52 o C. Several groups have previously reported that unlike Au nanorods, AuNPs do not usually generate high temperatures. 12 Our investigation showed that the non-aggregated AuNPs generated limited heat of up to 35 o C. However, the final formulation, which is a combination of AuNPs along with a PS and polymers, led to the aggregation of several AuNPs within a single hybrid nanoparticle. Therefore, PheoA-HA/AuNPs generated greater heat compared with the free AuNPs alone.…”

Section: Resultsmentioning

confidence: 71%

“…11 Previous studies have reported that illuminated AuNPs within tumors can interact with external lasers and produce enough localized heat to destroy the tumor with little damage to the surrounding healthy tissue. 12,13 In combination with pheophorbide-A (PheoA), AuNPs could serve as a multifunctional theranostic nano-agent for cancer treatments with the potential for use as an efficient PS delivery platform for PDT. 14 In this study, we report that AuNPs encapsulated by PheoA-conjugated hyaluronic acid (HA) may target the CD44 receptors of cells and produce promising therapeutic effects against lung cancer cells (A549).…”

Section: Introductionmentioning

confidence: 99%

Hybrid photoactive nanomaterial composed of gold nanoparticles, pheophorbide-A and hyaluronic acid as a targeted bimodal phototherapy

et al. 2015

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Modern cancer research is largely focused on the design and development of multifunctional nanomaterials for cancer therapy and diagnosis. In this study, we fabricated a theranostic nanomaterial known as a photomedicine that combines a photothermal therapy (PTT), gold nanoparticles (AuNPs), a photodynamic therapy (PDT), pheophorbide-A (PheoA), and a cancer-targeting agent, hyaluronic acid (HA); this photomedicine also acts as a bimodal phototherapy. The combination of AuNPs and PheoA exerts a synergistic effect on PTT and PDT when irradiated by a laser source with a specific excitation wavelength. When excited by an external laser source, the hybrid nanomedicine generates singlet oxygen from PheoA while simultaneously generating heat from the AuNP, thus demonstrating a higher efficacy than any of the individual agents. The presence of HA on the outer surface of the Au accelerates the cellular uptake of the nanomedicine through CD44 receptors and prevents nonspecific accumulation of the drug in non-cancerous cells. The multifunctional nanoparticles have a diameter of ~70 nm and show constant stability in different conditions for up to a week of observation. In vitro and in vivo studies have demonstrated that multifunctional nanomaterials selectively target cells overexpressing CD44 receptor. In vitro photo-activity assays in the lung cancer cell line (A549) show that over 95% of the cells were dead upon laser irradiation. In brief, this newly developed nanomaterial rapidly accumulates in the tumor within 3 h of IV administration and inhibits tumor growth by 95% upon laser irradiation compared with a saline-treated tumor model observed for 24 days.

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“…Several research groups have developed activatable aptamer-based methods which can be triggered by cancer biomarkers [42], membrane proteins, extracellular proteases [43], or cellular environments (e.g., pH) [44] or by other external stimuli, including artificial molecular switches [45]. For example, combination of a photosensitizer and ASP results in a switchable aptamer system which offers a reliable and versatile approach to the molecular mediation of singlet oxygen generation [46].…”

Section: Molecular Engineering Of a Switchable Aptamermentioning

confidence: 99%

Molecular Engineering to Enhance Aptamer Functionality

Han

Tan

2015

Aptamers Selected by Cell-Selex for Theranostics

Self Cite

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Rapid development of bioanalysis and biomedicine requires enhanced and multiple functionality of aptamers. The field of molecular engineering has advanced to a stage where more and more molecular functions can be rationally designed in a predictable manner. By combining these two fields together, aptamerbased molecular engineering is able to tune the functionalities of aptamers toward more complicated and effective biological and biomedical applications. In this chapter, we focus on introducing the substantial progress in the development of using smart ways to broaden the multifunctional and logical applications of aptamers.

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Assembly of Aptamer Switch Probes and Photosensitizer on Gold Nanorods for Targeted Photothermal and Photodynamic Cancer Therapy

Cited by 344 publications

References 38 publications

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Hybrid photoactive nanomaterial composed of gold nanoparticles, pheophorbide-A and hyaluronic acid as a targeted bimodal phototherapy

Molecular Engineering to Enhance Aptamer Functionality

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