Near-infrared Light-responsive Drug Research Articles

Targeted co-delivery of curcumin and erlotinib by MoS2 nanosheets for the combination of synergetic chemotherapy and photothermal therapy of lung cancer

BackgroundCurcumin (Cur), a bioactive component of Chinese traditional medicine, has demonstrated inhibitory properties against cancer cell proliferation while synergistically enhancing the anticancer efficacy of erlotinib (Er). However, the individual limitations of both drugs, including poor aqueous solubility, lack of targeting ability, short half-life, etc., and their distinct pharmacokinetic profiles mitigate or eliminate their combined antitumor potential.ResultsIn this study, we developed a molybdenum disulfide (MoS2)-based delivery system, functionalized with polyethylene glycol (PEG) and biotin, and co-loaded with Cur and Er, to achieve efficient cancer therapy. The MoS2-PEG-Biotin-Cur/Er system effectively converted near-infrared (NIR) light into heat, thereby inducing direct photothermal ablation of cancer cells and promoting controlled release of Cur and Er. Biotin-mediated tumor targeting facilitated the selective accumulation of MoS2-PEG-Biotin-Cur/Er at the tumor site, thus enhancing the synergistic antitumor effects of Cur and Er. Remarkably, MoS2-PEG-Biotin-Cur/Er achieved the combination of synergistic chemotherapy and photothermal therapy (PTT) upon NIR irradiation, effectively suppressing lung cancer cell proliferation and inhabiting tumor growth in vivo.ConclusionsThe as-synthesized MoS2-PEG-Biotin-Cur/Er, featuring high targeting ability, NIR light-responsive drug release, and the integration of synergistic chemotherapy and PTT, may provide a promising strategy for the treatment of lung cancer in clinical practice.Graphical

All-In-One Second Near-Infrared Light-Responsive Drug Delivery System for Synergistic Chemo-Photothermal Therapy.

Light-responsive nanocarrier-based drug delivery systems (NDDSs), due to their unique advantages such as safety, minimal cross-reaction, and spatiotemporal precision, have received wide attention. Notably, second near-infrared (NIR-II) light, which has a high penetration depth for manipulating NDDSs to release drugs, is in high demand. Herein, polyethylene glycol (PEG)-modified hollow CuxS nanoparticles (NPs) are developed as an all-in-one NIR-II light-responsive NDDS for synergistic chemo-photothermal therapy. First, CuxS-PEG NPs were prepared under mild conditions by using Cu2O NPs as sacrificial templates. The morphology, photothermal effect, drug loading/releasing abilities, and synergistic chemo-photothermal therapy of CuxS-PEG NPs have been investigated. The CuxS-PEG NPs with hollow structures showed a high drug loading capacity (∼255 μg Dox per mg of CuxS NPs) and stimuli-responsive drug release triggered by NIR-II laser irradiation. The synergistic chemo-photothermal therapy based on the Dox/CuxS-PEG NPs showed 98.5% tumor elimination. Our study emphasizes the great potential of CuxS-PEG NPs as an all-in-one NIR-II light-responsive NDDS for applications in biomedicine.

Black phosphorus-incorporated titanium dioxide nanotube arrays for near-infrared–triggered drug delivery

Inflammatory reaction after implantation is a serve complication of medical implants. Here, we propose a near-infrared (NIR) light stimulus-responsive drug-eluting platform based on titanium dioxide nanotube (TNT) arrays. Nano-sized black phosphorus (BP) prepared using a liquid exfoliation method served as a photothermal agent and were incorporated with TNTs, imparting TNTs NIR stimulus-responsive activity. The combination of BP and TNTs exhibited excellent photothermal conversion performance. Ibuprofen, a commonly used anti-inflammatory drug, was selected as the model drug and loaded on the NIR-responsive functional TNTs. A coating of 1-tetradecanol (TD) was used as a thermosensitive gatekeeper to prevent drug release at normal body temperature. Upon exposure to NIR light, the NIR-responsive drug delivery system transformed light energy to thermal energy that melted the TD layer and led to drug release from the reservoir. Furthermore, the combination of BP and TNTs showed enhanced biomineralization performance because of the degradation of BP into phosphate. Moreover, BP-modified TNTs showed no obvious cytotoxicity to MC3T3-E1 cells. Thus, this NIR light-responsive drug delivery system shows potential for controlled drug delivery in Ti-based orthopedic implants to overcome the challenges of tissue inflammation after implantation.

Tumor acidity and near-infrared light responsive drug delivery MoS2-based nanoparticles for chemo-photothermal therapy

The rational design of tumor microenvironment (TME)- multifunctional stimuli-responsive nanocomposites is appealing for effective cancer treatment. However, multidrug resistance remains an obstacle to construct responsive oncotherapy. Herein, a novel MoS2/PDA-TPP nanocomposite loaded with chemotherapy drug of doxorubicin (DOX) is designed for TME dual-response and synergistically enhanced anti-tumor therapy based on the tumor-specific mitochondria accumulation ability and photothermal (PTT) therapy. In detail, the designed MoS2/PDA-TPP nanoplatform can act as a pH-responsive dissociation to endow fast release of DOX under an acidic TME and simultaneously improve the efficiency of PTT. Moreover, the mechanism shows that MoS2/PDA-TPP trigger mitochondrial-dependent apoptosis by producing reactive oxygen species (ROS) and reducing mitochondrial membrane potential (MMP). Most importantly, during PTT procedure, hyperthermia up to 50 °C can effectively induce tumor cell death without causing severe inflammation to adjacent tissues. Tumor targeting double stimulation response of nanocomposites is a novel idea to overcome drug resistance, which will provide a more effective strategy for solving practical problems.

NIR light-assisted phototherapies for bone-related diseases and bone tissue regeneration: A systematic review.

Recently, the rapid development of biomaterials has induced great interest in the precisely targeted treatment of bone-related diseases, including bone cancers, infections, and inflammation. Realizing noninvasive therapeutic effects, as well as improving bone tissue regeneration, is essential for the success of bone‑related disease therapies. In recent years, researchers have focused on the development of stimuli-responsive strategies to treat bone-related diseases and to realize bone regeneration. Among the various external stimuli for targeted therapy, near infrared (NIR) light has attracted considerable interests due to its high tissue penetration capacity, minimal damage toward normal tissues, and easy remote control properties. The main objective of this systematic review was to reveal the current applications of NIR light-assisted phototherapy for bone-related disease treatment and bone tissue regeneration. Database collection was completed by June 1, 2020, and a total of 81 relevant studies were finally included. We outlined the various therapeutic applications of photothermal, photodynamic and photobiomodulation effects under NIR light irradiation for bone‑related disease treatment and bone regeneration, based on the retrieved literatures. In addition, the advantages and promising applications of NIR light-responsive drug delivery systems for spatiotemporal-controlled therapy were summarized. These findings have revealed that NIR light-assisted phototherapy plays an important role in bone-related disease treatment and bone tissue regeneration, with significant promise for further biomedical and clinical applications.

Microfluidic fabrication of fatty alcohol-based microparticles for NIR light-triggered drug release

The development of photo-triggered drug delivery system is promising for the temporal and spatial control of drug release. However, most of the progress in photothermal drug delivery has been focused on nanosized particles which can be removed from the injected sites by exocytosis. In this study, injectable and implantable near-infrared (NIR) light-responsive microparticles are fabricated using droplet-based microfluidics. The particles are composed of 1-tetradecanol, as a class of non-toxic phase change material, and IR780, as a NIR-absorbing photothermal agent. Doxorubicin, an anticancer drug, is encapsulated in the particles to obtain NIR light-responsive anticancer drug carriers. The photothermal response of IR780 to NIR irradiation facilitates the release of the encapsulated drug through the melting of 1-tetradecanol and demonstrates the NIR light-responsive drug release. This study shows that IR780-encapsulated 1-tetradecanol microparticles fabricated by droplet-based microfluidics have great potential as injectable and implantable drug carriers featuring NIR light-sensitive drug release.

DNA decorated Cu9S5 nanoparticles as NIR light responsive drug carriers for tumor chemo-phototherapy.

Recently, near-infrared (NIR) light responsive drug delivery systems have attracted much attention for tumor therapy. Herein, we have successfully constructed a smart nanocarrier system Cu9S5-PEI-DNA-DOX (labelled as CPD-DOX) based on the self-assembly of hydrophobic Cu9S5 nanoparticles (NPs), poly(ethylene imine) (PEI), double-stranded DNA (dsDNA) segments and the anti-cancer drug doxorubicin (DOX). Among them, Cu9S5 NPs can serve as a nano-transducer for absorbing and converting near-infrared light to heat. Then, the hydrophobic layer of Cu9S5 NPs is coated with the dendritic polymer PEI through a simple approach. According to the temperature of the tumor tissue and the photothermal effect of Cu9S5 NPs, we specially designed a DNA sequence with a suitable melting temperature for NIR-light-promoted denaturation of DNA helices and drug release when DOX intercalated into the dsDNA through noncovalent interaction. Notably, the DOX-loaded dsDNA can be decorated on the surface of Cu9S5 NPs by convenient electrostatic adsorption rather than chemical bonding. The experimental results show that dsDNA can maintain a stable helical structure under physiological conditions but unzip the helix to release DOX upon NIR irradiation. Therefore, DOX can be safely delivered and released into cancer cells to exert anticancer effects. Based on in vitro cell cytotoxicity experiments, the CPD-DOX system has a synergistic effect for cancer cell apoptosis or death because of both the cytotoxicity of light-triggered DOX release and the Cu9S5-NP-mediated photothermal ablation effect. It is expected that the facile synthesis and low cost nanocarrier can improve the anticancer effect in contrast to the single chemotherapy or photothermal therapy mode.

Programmed near-infrared light-responsive drug delivery system for combined magnetic tumor-targeting magnetic resonance imaging and chemo-phototherapy.

As we all know, a series of shortcomings of conventional chemotherapy such as limited stability, rapid clearing and non-specific tumor targeting ability remain a significant challenge to achieve successful clinical therapeutic efficiency in cancer treatments. Fortunately, developing drug delivery system under the assistance of multifunctional nanocarries might be a great idea. For the first time, we proposed an intelligent drug delivery system by capping DOX-loaded hollow mesoporous CuS nanoparticles (HMCuS NPs) with multifunctional IONPs to integrate programmed functions including enhanced PTT effect, sophisticated controlled drug release, magnetic targeting property and MR imaging. The results showed HMCuS/DOX@IONP-PEG could significantly enhance anti-tumor therapeutic efficacy due to the synergistic combination of chemo-phototherapy. By this delicate design, we believe such smart and extreme versatile all-in-one drug delivery platform could arouse broad interests in the fields of biomaterials, nanotechnology, and drug delivery system.

Progress in the Field of Constructing Near-Infrared Light-Responsive Drug Delivery Platforms.

Stimuli-responsive materials have taken replace of traditional drug carriers due to their ability to achieve controlled release of their encapsulated contents. A variety of sensitive materials, such as polymers that respond to pH, light, and magnetic fields, are widely used to construct drug carriers, and achieved good results. Specifically, near-infrared light (NIR) responsive materials are of particular interest in drug delivery, as NIR can penetrate body tissue and is minimally absorbed by the body's water and hemoglobin and is less harmful to healthy cells than UV or visible light. Thus, the near-infrared excitation drug delivery systems (NIRDDSs) have some essential advantages just like being efficient to kill tumor cells, accurate to achieve the tumor sites and less damage to human body. Also, in the process of building the carriers, we may achieve a combination of controlled release chemotherapy, photothermal therapy (PTT) or photodynamic therapy (PDT). In addition, besides utilizing as drug delivery platforms, some carriers can achieve multifunctional tumor diagnosis and treatment, such as magnetic resonance imaging, optical imaging, drug carriers and PTT. In this review, based on the mechanism of NIR, we highlight diverse near-infrared light-responsive drug delivery platforms and recent advances in the development of NIRDDSs for cancer therapy primarily.

CuS@mSiO2-PEG core-shell nanoparticles as a NIR light responsive drug delivery nanoplatform for efficient chemo-photothermal therapy.

We report a facile and low-cost approach to design a difunctional nanoplatform (CuS@mSiO2-PEG) as a near-infrared (NIR) light responsive drug delivery system for efficient chemo-photothermal therapy. The nanoplatform demonstrated good biocompatibility and colloidal stability, as well as high loading capacity for the anticancer drug (26.5 wt% for doxorubicin (DOX)). The CuS nanocrystals (core) within these CuS@mSiO2-PEG core-shell nanoparticles can effectively absorb and convert NIR light to fatal heat under NIR light irradiation for photothermal therapy, and the release of DOX from the mesoporous silica (shell) can be triggered by pH and NIR light for chemotherapy. When the CuS@mSiO2-PEG/DOX nanocomposites were irradiated by 980 nm light, both chemotherapy and photothermal therapy were simultaneously driven, resulting in a synergistic effect for killing cancer cells. Importantly, compared with chemotherapy or photothermal treatment alone, the combined therapy significantly improved the therapeutic efficacy.

Responsive polymer-fluorescent carbon nanoparticle hybrid nanogels for optical temperature sensing, near-infrared light-responsive drug release, and tumor cell imaging.

Fluorescent carbon nanoparticles (FCNPs) have been successfully immobilized into poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)] nanogels based on one-pot precipitation copolymerization of NIPAM monomers with hydrogen bonded FCNP-AAm complex monomers in water. The resultant poly(NIPAM-AAm)-FCNP hybrid nanogels can combine functions from each building block for fluorescent temperature sensing, cell imaging, and near-infrared (NIR) light responsive drug delivery. The FCNPs in the hybrid nanogels not only emit bright and stable photoluminescence (PL) and exhibit up-conversion PL properties, but also increase the loading capacity of the nanogels for curcumin drug molecules. The reversible thermo-responsive swelling/shrinking transition of the poly(NIPAM-AAm) nanogel can not only modify the physicochemical environment of the FCNPs to manipulate the PL intensity for sensing the environmental temperature change, but also regulate the releasing rate of the loaded anticancer drug. In addition, the FCNPs embedded in the nanogels can convert the NIR light to heat, thus an exogenous NIR irradiation can further accelerate the drug release and enhance the therapeutic efficacy. The hybrid nanogels can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells upon laser excitation. The demonstrated hybrid nanogels with nontoxic and optically active FCNPs immobilized in responsive polymer nanogels are promising for the development of a new generation of multifunctional materials for biomedical applications.

Magnetic iron oxide-fluorescent carbon dots integrated nanoparticles for dual-modal imaging, near-infrared light-responsive drug carrier and photothermal therapy.

Multifunctional hybrid nanoparticles (NPs, ∼100 nm) that combine magnetic Fe3O4 nanocrystals and fluorescent carbon dots (CDs) in porous carbon (C) were successfully synthesized using a one-pot solvothermal method by simply increasing the H2O2 concentration. The resultant Fe3O4@C-CDs hybrid NPs not only demonstrate excellent magnetic responsive properties (Ms = 32.5 emu g-1) and magnetic resonance imaging ability (r = 674.4 mM-1 s-1) from the Fe3O4 nanocrystal core, but also exhibit intriguing photoluminescent (quantum yield ∼6.8%) properties including upconversion fluorescence and excellent photostability from the CDs produced in the porous carbon. The hybrid NPs can enter the intracellular region and illuminate mouse melanoma B16F10 cells under different excitation wavelengths. Meanwhile, the mesoporous carbon shell and hydrophilic surface functional groups endow the hybrid NPs with high loading capacity (835 mg g-1) for the anti-cancer drug doxorubicin and excellent stability in aqueous solutions. More importantly, the hybrid NPs can absorb and convert near-infrared (NIR) light to heat due to the existence of CDs, and thus, can realise NIR-controlled drug release and combined photothermo/chemotherapy for high therapeutic efficacy. Such nanostructured Fe3O4@C-CDs hybrid NPs demonstrate great promise towards advanced nanoplatforms for simultaneous imaging diagnostics and high efficacy therapy.

Multifunctional Fe3O4@C@Ag hybrid nanoparticles as dual modal imaging probes and near-infrared light-responsive drug delivery platform

Multifunctional nanocarriers based on Fe3O4@C@Ag hybrid nanoparticles with a diameter of 200 nm were fabricated by a facile method. Silver (Ag) nanoparticles were deposited onto the surface of Fe3O4@C nanospheres in dimethyl formamide (DMF) solution by reducing silver nitrate (AgNO3) with glucose. The nanocarriers of doxorubicin (DOX) with a high loading content of 997 mg/g and near-infrared (NIR) light-responsive drug delivery based on Ag nanoparticles were realized. Strong fluorescence can be observed in cell nucleus due to the presence of DOX after irradiated by NIR, and most cells were in the state of apoptosis, which indicates NIR-regulated drug release was realized. Moreover, measurements show that the nanocarriers could also be used as magnetic resonance imaging (MRI) contrast agents and fluorescent probes. The combination of synergistic NIR controlled drug release and dual modal imaging of MRI and two-photon fluorescence (TPF) imaging could lead to a potential multifunctional system for biomedical diagnosis and therapy.

Near‐Infrared Light‐Triggered, Targeted Drug Delivery to Cancer Cells by Aptamer Gated Nanovehicles

A novel cell-targeting, near-infrared light-responsive drug delivery platform based on mesoporous silica-coated gold nanorods that are surface-functionalized with aptamer DNA is constructed. Aptamer DNA is used as both capping and targeting agent. In vitro studies show the feasibility of using this nanocarrier for targeted and noninvasive remote controlled drug delivery and photothermal therapy.

Near-Infrared Light-Responsive Core–Shell Nanogels for Targeted Drug Delivery

A near-infrared light-responsive drug delivery platform based on Au-Ag nanorods (Au-Ag NRs) coated with DNA cross-linked polymeric shells was constructed. DNA complementarity has been applied to develop a polyacrylamide-based sol-gel transition system to encapsulate anticancer drugs into the gel scaffold. The Au-Ag NR-based nanogels can also be readily functionalized with targeting moieties, such as aptamers, for specific recognition of tumor cells. When exposed to NIR irradiation, the photothermal effect of the Au-Ag NRs leads to a rapid rise in the temperature of the surrounding gel, resulting in the fast release of the encapsulated payload with high controllability. In vitro study confirmed that aptamer-functionalized nanogels can be used as drug carriers for targeted drug delivery with remote control capability by NIR light with high spatial/temporal resolution.