scholarly journals Cation-responsive and photocleavable hydrogels from non-canonical amphiphilic DNA nanostructures

Author(s):  
Giacomo Fabrini ◽  
Aisling Minard ◽  
Ryan A. Brady ◽  
Marco Di Antonio ◽  
Lorenzo Di Michele

Thanks to its biocompatibility, versatility and programmable interactions, DNA has been proposed as a building block for functional, stimuli-responsive frameworks with applications in biosensing, tissue engineering and drug delivery. Of particular importance for in vivo applications is the possibility of making such nano-materials responsive to physiological stimuli. Here we demonstrate how combining noncanonical DNA G-quadruplex (G4) structures with amphiphilic DNA constructs yields nanostructures, which we termed "Quad-Stars", capable of assembling into responsive hydrogel particles via a straightforward, enzyme-free, one-pot reaction. The embedded G4 structures allow one to trigger and control the assembly/disassembly in a reversible fashion by adding or removing K+ ions. Furthermore, the hydrogel aggregates can be photodisassembled upon near-UV irradiation in the presence of a porphyrin photosensitiser. The combined reversibility of assembly, responsiveness and cargo-loading capabilities of the hydrophobic moieties make Quad-Stars a promising candidate for biosensors and responsive drug delivery carriers.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1135
Author(s):  
Kristin Entzian ◽  
Achim Aigner

Conventional cancer chemotherapies often exhibit insufficient therapeutic outcomes and dose-limiting toxicity. Therefore, there is a need for novel therapeutics and formulations with higher efficacy, improved safety, and more favorable toxicological profiles. This has promoted the development of nanomedicines, including systems for drug delivery, but also for imaging and diagnostics. Nanoparticles loaded with drugs can be designed to overcome several biological barriers to improving efficiency and reducing toxicity. In addition, stimuli-responsive nanocarriers are able to release their payload on demand at the tumor tissue site, preventing premature drug loss. This review focuses on ultrasound-triggered drug delivery by nanocarriers as a versatile, cost-efficient, non-invasive technique for improving tissue specificity and tissue penetration, and for achieving high drug concentrations at their intended site of action. It highlights aspects relevant for ultrasound-mediated drug delivery, including ultrasound parameters and resulting biological effects. Then, concepts in ultrasound-mediated drug delivery are introduced and a comprehensive overview of several types of nanoparticles used for this purpose is given. This includes an in-depth compilation of the literature on the various in vivo ultrasound-responsive drug delivery systems. Finally, toxicological and safety considerations regarding ultrasound-mediated drug delivery with nanocarriers are discussed.


Polymers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1285
Author(s):  
Louise Van Gheluwe ◽  
Igor Chourpa ◽  
Coline Gaigne ◽  
Emilie Munnier

Progress in recent years in the field of stimuli-responsive polymers, whose properties change depending on the intensity of a signal, permitted an increase in smart drug delivery systems (SDDS). SDDS have attracted the attention of the scientific community because they can help meet two current challenges of the pharmaceutical industry: targeted drug delivery and personalized medicine. Controlled release of the active ingredient can be achieved through various stimuli, among which are temperature, pH, redox potential or even enzymes. SDDS, hitherto explored mainly in oncology, are now developed in the fields of dermatology and cosmetics. They are mostly hydrogels or nanosystems, and the most-used stimuli are pH and temperature. This review offers an overview of polymer-based SDDS developed to trigger the release of active ingredients intended to treat skin conditions or pathologies. The methods used to attest to stimuli-responsiveness in vitro, ex vivo and in vivo are discussed.


Nanomedicine ◽  
2021 ◽  
Author(s):  
Xuandi Lai ◽  
Xinran Geng ◽  
Mengqing Li ◽  
Mengxiong Tang ◽  
Qiong Liu ◽  
...  

Aim: This work aims to develop an injectable nano-drug delivery system to overcome tumor multidrug resistance (MDR). Methods: A drug delivery nanoplatform based on PEGylated PLGA with glutathione (GSH) responsivity was constructed for dual delivery of doxorubicin and curcumin (termed DCNP), and its MDR reversal efficiency was studied in vitro and in vivo. Results: The DCNPs exhibited a rapid drug release profile under high GSH concentration and could enhance the cellular uptake and cytotoxicity of doxorubicin to MDR cancer cells. Moreover, the DCNPs showed better biocompatibility, longer blood circulation and enhanced antitumor efficiency compared with free drugs. Conclusion: The GSH-responsive nanocarrier is believed to be a promising candidate for overcoming tumor MDR.


Nanomaterials ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 91 ◽  
Author(s):  
Chuan Zhang ◽  
Yuzhuo Wang ◽  
Yue Zhao ◽  
Hou Liu ◽  
Yueqi Zhao ◽  
...  

The chemotherapy of stimuli-responsive drug delivery systems (SDDSs) is a promising method to enhance cancer treatment effects. However, the low efficiency of chemotherapy drugs and poor degradation partly limit the application of SDDSs. Herein, we report doxorubicin (DOX)-loading mixed micelles for biotin-targeting drug delivery and enhanced photothermal/photodynamic therapy (PTT/PDT). Glutathione (GSH)-responsive mixed micelles were prepared by a dialysis method, proportionally mixing polycaprolactone-disulfide bond-biodegradable photoluminescent polymer (PCL-SS-BPLP) and biotin-polyethylene glycol-cypate (biotin-PEG-cypate). Chemically linking cypate into the mixed micelles greatly improved cypate solubility and PTT/PDT effect. The micelles also exhibited good monodispersity and stability in cell medium (~119.7 nm), low critical micelles concentration, good biodegradation, and photodecomposition. The high concentration of GSH in cancer cells and near-infrared light (NIR)-mediated cypate decomposition were able to achieve DOX centralized release. Meanwhile, the DOX-based chemotherapy combined with cypate-based NIR-triggered hyperthermia and reactive oxygen species could synergistically induce HepG2 cell death and apoptosis. The in vivo experiments confirmed that the micelles generated hyperthermia and achieved a desirable therapeutic effect. Therefore, the designed biodegradable micelles are promising safe nanovehicles for antitumor drug delivery and chemo/PTT/PDT combination therapy.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3295
Author(s):  
Federica Foglietta ◽  
Loredana Serpe ◽  
Roberto Canaparo

Stimuli-responsive drug-delivery systems (DDSs) have emerged as a potential tool for applications in healthcare, mainly in the treatment of cancer where versatile nanocarriers are co-triggered by endogenous and exogenous stimuli. Two-dimensional (2D) cell cultures are the most important in vitro model used to evaluate the anticancer activity of these stimuli-responsive DDSs due to their easy manipulation and versatility. However, some limitations suggest that these in vitro models poorly predict the outcome of in vivo studies. One of the main drawbacks of 2D cell cultures is their inadequate representation of the 3D environment’s physiological complexity, which sees cells interact with each other and the extracellular matrix (ECM) according to their specific cellular organization. In this regard, 3D cancer models are a promising approach that can overcome the main shortcomings of 2D cancer cell cultures, as these in vitro models possess many peculiarities by which they mimic in vivo tumors, including physiologically relevant cell–cell and cell–ECM interactions. This is, in our opinion, even more relevant when a stimuli-responsive DDS is being investigated. In this review, we therefore report and discuss endogenous and exogenous stimuli-responsive DDSs whose effectiveness has been tested using 3D cancer cell cultures.


2021 ◽  
Vol 27 ◽  
Author(s):  
Mayank Handa ◽  
Ajit Singh ◽  
S.J.S. Flora ◽  
Rahul Shukla

Background: Recent past decades have reported emerging of polymeric nanoparticles as a promising technique for controlled and targeted drug delivery. As nanocarriers, they have high drug loading and delivery to the specific site or targeted cells with an advantage of no drug leakage within en route and unloading of a drug in a sustained fashion at the site. These stimuli-responsive systems are functionalized in dendrimers, metallic nanoparticles, polymeric nanoparticles, liposomal nanoparticles, quantum dots. Purpose of Review: The authors reviewed the potential of smart stimuli-responsive carriers for therapeutic application and their behavior in external or internal stimuli like pH, temperature, redox, light, and magnet. These stimuli-responsive drug delivery systems behave differently in In vitro and In vivo drug release patterns. Stimuli-responsive nanosystems include both hydrophilic and hydrophobic systems. This review highlights the recent development of the physical properties and their application in specific drug delivery. Conclusion: The stimuli (smart, intelligent, programmed) drug delivery systems provide site-specific drug delivery with potential therapy for cancer, neurodegenerative, lifestyle disorders. As development and innovation, the stimuli-responsive based nanocarriers are moving at a fast pace and huge demand for biocompatible and biodegradable responsive polymers for effective and safe delivery.


Physiology ◽  
1989 ◽  
Vol 4 (4) ◽  
pp. 146-151 ◽  
Author(s):  
G Gregoriadis

Understanding of the behavior and control of liposomes in vivo has led to their successful use as a drug delivery system in the treatment or prevention of a wide spectrum of diseases in experimental animals and, more recently, in clinical trials.


2017 ◽  
Vol 97 (1) ◽  
pp. 189-225 ◽  
Author(s):  
Wujin Sun ◽  
Quanyin Hu ◽  
Wenyan Ji ◽  
Grace Wright ◽  
Zhen Gu

Physiological characteristics of diseases bring about both challenges and opportunities for targeted drug delivery. Various drug delivery platforms have been devised ranging from macro- to micro- and further into the nanoscopic scale in the past decades. Recently, the favorable physicochemical properties of nanomaterials, including long circulation, robust tissue and cell penetration attract broad interest, leading to extensive studies for therapeutic benefits. Accumulated knowledge about the physiological barriers that affect the in vivo fate of nanomedicine has led to more rational guidelines for tailoring the nanocarriers, such as size, shape, charge, and surface ligands. Meanwhile, progresses in material chemistry and molecular pharmaceutics generate a panel of physiological stimuli-responsive modules that are equipped into the formulations to prepare “smart” drug delivery systems. The capability of harnessing physiological traits of diseased tissues to control the accumulation of or drug release from nanomedicine has further improved the controlled drug release profiles with a precise manner. Successful clinical translation of a few nano-formulations has excited the collaborative efforts from the research community, pharmaceutical industry, and the public towards a promising future of smart drug delivery.


2020 ◽  
Vol 27 (15) ◽  
pp. 2494-2513 ◽  
Author(s):  
João A. Oshiro-Júnior ◽  
Camila Rodero ◽  
Gilmar Hanck-Silva ◽  
Mariana R. Sato ◽  
Renata Carolina Alves ◽  
...  

Stimuli-responsive drug-delivery nanocarriers (DDNs) have been increasingly reported in the literature as an alternative for breast cancer therapy. Stimuli-responsive DDNs are developed with materials that present a drastic change in response to intrinsic/chemical stimuli (pH, redox and enzyme) and extrinsic/physical stimuli (ultrasound, Near-infrared (NIR) light, magnetic field and electric current). In addition, they can be developed using different strategies, such as functionalization with signaling molecules, leading to several advantages, such as (a) improved pharmaceutical properties of liposoluble drugs, (b) selectivity with the tumor tissue decreasing systemic toxic effects, (c) controlled release upon different stimuli, which are all fundamental to improving the therapeutic effectiveness of breast cancer treatment. Therefore, this review summarizes the use of stimuli-responsive DDNs in the treatment of breast cancer. We have divided the discussions into intrinsic and extrinsic stimuli and have separately detailed them regarding their definitions and applications. Finally, we aim to address the ability of these stimuli-responsive DDNs to control the drug release in vitro and the influence on breast cancer therapy, evaluated in vivo in breast cancer models.


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