Selective Light-Triggered Release of DNA from Gold Nanorods Switches Blood Clotting On and Off

Puig, Helena de; Cifuentes‐Rius, Anna; Flemister, Dorma; Baxamusa, Salmaan H.; Hamad‐Schifferli, Kimberly

doi:10.1371/journal.pone.0068511

Cited by 30 publications

(24 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, as a synthetic biomaterial, Apt‐NMed is completely biocompatible and biodegradable, and will not cause adverse effects in the human body. The majority of materials previously conjugated to aptamers, such as inorganic and organic carriers, including gold or magnetic nanomaterials, single‐walled carbon nanotubes, mesoporous silica nanoparticles, quantum dots, liposomes, copolymers, and protein‐based nanomaterials are foreign to the human body and may pose unknown risks for in vivo use. It is noteworthy that Apt‐NMed can be synthesized by a simple method, which is highly reproducible, cost‐effective, and can be easily scaled up for industrial production of this multifunctional nanomedicine.…”

Section: Discussionmentioning

confidence: 99%

Self‐Assembled Aptamer‐Nanomedicine for Targeted Chemotherapy and Gene Therapy

Zhao

Zeng

2017

Small

View full text Add to dashboard Cite

Chemotherapy is the mainstream treatment of anaplastic large cell lymphoma (ALCL). However, chemotherapy can cause severe adverse effects in patients because it is not ALCL-specific. In this study, a multifunctional aptamer-nanomedicine (Apt-NMed) achieving targeted chemotherapy and gene therapy of ALCL is developed. Apt-NMed is formulated by self-assembly of synthetic oligonucleotides containing CD30-specific aptamer and anaplastic lymphoma kinase (ALK)-specific siRNA followed by self-loading of the chemotherapeutic drug doxorubicin (DOX). Apt-NMed exhibits a well-defined nanostructure (diameter 59 mm) and stability in human serum. Under aptamer guidance, Apt-NMed specifically binds and internalizes targeted ALCL cells. Intracellular delivery of Apt-NMed triggers rapid DOX release for targeted ALCL chemotherapy and intracellular delivery of the ALK-specific siRNA induced ALK oncogene silencing, resulting in combined therapeutic effects. Animal model studies reveal that upon systemic administration, Apt-NMed specifically targets and selectively accumulates in ALCL tumor site, but does not react with off-target tumors in the same xenograft mouse. Importantly, Apt-NMed not only induces significantly higher inhibition in ALCL tumor growth, but also causes fewer or no side effects in treated mice compared to free DOX. Moreover, Apt-NMed treatment markedly improves the survival rate of treated mice, opening a new avenue for precision treatment of ALCL.

show abstract

Section: Discussionmentioning

confidence: 99%

Self‐Assembled Aptamer‐Nanomedicine for Targeted Chemotherapy and Gene Therapy

Zhao

Zeng

2017

Small

View full text Add to dashboard Cite

show abstract

“…Consequently, inhibition and restoration of the blood clotting time could be precisely controlled. [90] In yet another light-triggered approach, Cohen & Bergkvist took advantage of virus-like particles and used them as nanocarriers. Consequently, they developed functional AS1411 aptamer-virus-like particles that delivered porphyrin photosensitizer for breast cancer photodynamic therapy.…”

Section: Aptamer-targeted Nanomedicinesmentioning

confidence: 99%

“…Representative schematic diagrams of stimuli-triggered drug delivery systems: (A) pH-triggered aptamer-targeted HAuNS for chemical drugs delivery, modified from reference [88]; (B) Light-triggered therapeutic aptamer controlled release system for blood clotting therapy, modified form reference [90]; (C) Specific targets triggered, switchable aptamer-targeted MSN drug delivery system, modified from reference [93]; (D) Light triggered, aptamer-targeted photothermal therapy model, modified from reference [96]; (E) Magnetic fields triggered, aptamer-targeted magnetic-hyperthermia model, modified from reference [97]; (F) Specific targets triggered, aptamer-targeted gold nanorods loaded with photosensitizer for combinational photothermal and photodynamic therapy, modified from reference [98]; (G) Light triggered, aptamer-targeted gold NPs loaded with photosensitizer and chemotherapeutic drugs for combinational photodynamic therapy and chemotherapy, modified from reference [99]. …”

Section: Figurementioning

confidence: 99%

“…Utilizing irradiation with light of different wavelengths, the thrombin‐specific aptamer and its antidote could be released separately and act as an ON/OFF switch for blood clotting. Consequently, inhibition and restoration of the blood clotting time could be precisely controlled . In yet another light‐triggered approach, Cohen and Bergkvist took advantage of virus‐like particles (VLPs) as nanocarriers.…”

Section: Aptamer‐targeted Nanomedicinesmentioning

confidence: 99%

See 1 more Smart Citation

Aptamers and Their Applications in Nanomedicine

Sun

2015

Small

146

View full text Add to dashboard Cite

Aptamers are composed of short RNA or single-stranded DNA sequences that, when folded into their unique three-dimensional conformation, can specifically bind to their cognate targets with high specificity and affinity. Although functionally similar to protein antibodies, oligonucleotide aptamers offer several advantages over protein antibodies in biomedical and clinical applications. Additionally, through the enhanced permeability and retention (EPR) effect, nanomedicines can improve the therapeutic index of a treatment and reduce side effects by enhancing accumulation at the disease site. However, this EPR effect is “passive targeting” to tumors and thus, may not be an ideal approach for targeted cancer therapy. To construct ligand-directed “active targeting” nano-based delivery systems, aptamer technology has been widely studied. The aptamer-equipped nanomedicines have been tested for in vitro diagnosis, in vivo imaging, targeted cancer therapy, theranostic approaches, sub-cellular molecule detection, food safety, and environment monitoring. This review will focus on the development of aptamer-conjugated nanomedicines and their application for in vivo imaging, targeted therapy, and theranostics. In some applications, aptamers can also be used as drug carriers or ON/OFF switches. Herein, some outstanding therapeutic approaches are also discussed on a case-by-case basis, such as an “on-command” release system and a combinational therapy strategy.

show abstract

“…16 However, despite the achievements on caged and light-switchable proteins mentioned in Mayer's review, further efforts should be made to provide milder strategies, especially considering the tissue damage associated with UV light and the complicated procedure to prepare caged proteins. 18 Use of NIR photons to restore protein activity inhibited by potent aptamerbased closed-loop structures can be achieved by conversion of radiant energy to heat. 17 For instance, Schifferli et al have reported an elegant approach in which NIR light was employed for the controlled release of anticoagulant and antidote for on/off switching of blood clotting.…”

Section: Introductionmentioning

confidence: 99%

Protein Activity Regulation: Inhibition by Closed-Loop Aptamer-Based Structures and Restoration by Near-IR Stimulation

Wang

Wei

et al. 2015

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Regulation of protein activity is vital for understanding the molecular mechanism of biological activities. In this work, protein activity is suppressed by proximity-dependent surface hybridization and subsequently restored by near-infrared (NIR) light stimulation. Specifically, by constructing closed-loop structures with two aptamer-based affinity ligands, significantly enhanced inhibition of thrombin activity is achieved compared to traditional single affinity ligand based inhibitors. Furthermore, the activity of inhibited thrombin is efficiently recovered under NIR light stimulation by using gold nanorods (AuNRs) as photothermal agents to disrupt the closed-loop structures. Real-time and in situ monitoring of the conversion of fibrinogen into fibrin catalyzed by both inhibited and recovered thrombin was performed with light scattering spectroscopy and laser scanning confocal microscopy (LSCM). Thrombin trapped in the closed-loop structures shows slow reaction kinetics, while the photothermally liberated thrombin displays largely recovered catalytic activity. Human plasma was further employed to demonstrate that both the inhibited and restored thrombin can be applied to clotting reaction in reality. This strategy provides protein activity regulation for studying the molecular basis of biological activities and can be further applied to potential areas such as metabolic pathway regulation and the development of protein-inhibitor pharmaceuticals.

show abstract

Selective Light-Triggered Release of DNA from Gold Nanorods Switches Blood Clotting On and Off

Cited by 30 publications

References 32 publications

Self‐Assembled Aptamer‐Nanomedicine for Targeted Chemotherapy and Gene Therapy

Self‐Assembled Aptamer‐Nanomedicine for Targeted Chemotherapy and Gene Therapy

Aptamers and Their Applications in Nanomedicine

Protein Activity Regulation: Inhibition by Closed-Loop Aptamer-Based Structures and Restoration by Near-IR Stimulation

Contact Info

Product

Resources

About