Photothermal Therapy Agents Research Articles

Marriage of black phosphorus and Cu2+ as effective photothermal agents for PET-guided combination cancer therapy

The use of photothermal agents (PTAs) in cancer photothermal therapy (PTT) has shown promising results in clinical studies. The rapid degradation of PTAs may address safety concerns but usually limits the photothermal stability required for efficacious treatment. Conversely, PTAs with high photothermal stability usually degrade slowly. The solutions that address the balance between the high photothermal stability and rapid degradation of PTAs are rare. Here, we report that the inherent Cu2+-capturing ability of black phosphorus (BP) can accelerate the degradation of BP, while also enhancing photothermal stability. The incorporation of Cu2+ into BP@Cu nanostructures further enables chemodynamic therapy (CDT)-enhanced PTT. Moreover, by employing 64Cu2+, positron emission tomography (PET) imaging can be achieved for in vivo real-time and quantitative tracking. Therefore, our study not only introduces an “ideal” PTA that bypasses the limitations of PTAs, but also provides the proof-of-concept application of BP-based materials in PET-guided, CDT-enhanced combination cancer therapy.

TICT-Based Near-Infrared Ratiometric Organic Fluorescent Thermometer for Intracellular Temperature Sensing.

Fluorescent thermometers with near-infrared (NIR) emission play an important role in visualizing the intracellular temperature with high resolution and investigating the cellular functions and biochemical activities. Herein, we designed and synthesized a donor-Π-acceptor luminogen, 2-([1,1'-biphenyl]-4-yl)-3-(4-((E)-4-(diphenylamino)styryl) phenyl) fumaronitrile (TBB) by Suzuki coupling reaction. TBB exhibited twisted intramolecular charge transfer-based NIR emission, aggregation-induced emission, and temperature-sensitive emission features. A ratiometric fluorescent thermometer was constructed by encapsulating thermosensitive NIR fluorophore TBB and Rhodamine 110 dye into an amphiphilic polymer matrix F127 to form TBB&R110@F127 nanoparticles (TRF NPs). TRF NPs showed a good temperature sensitivity of 2.37%·°C-1, wide temperature response ranges from 25 to 65 °C, and excellent temperature-sensitive emission reversibility. Intracellular thermometry experiments indicated that TRF NPs could monitor the cellular temperature change from 25 to 53 °C for Hep-G2 cells under the photothermal therapy agent heating process, indicating the considerable potential applications of TRF NPs in the biological thermometry field.

Multifunctional HNT@Fe3O4@PPy@DOX Nanoplatform for Effective Chemo-Photothermal Combination Therapy of Breast Cancer with MR Imaging.

Multifunctional nanoparticles for imaging and treatment in cancer are getting more and more attention recently. Herein, halloysite nanotubes (HNTs), natural clay nanotubes, are designed as multifunctional nanoplatform for targeted delivering photothermal therapy agents and chemotherapeutic drugs. Fe3O4 was anchored on the outer surfaces of HNTs and then doxorubicin (DOX) was loaded on the nanotubes. Afterward, a layer of polypyrrole (PPy), as photothermal agent, was wrapped on the tubes. The nanoplatform of HNT@Fe3O4@PPy@DOX can be guided to tumor tissue by an external magnetic field, and then performs chemo-photothermal combined therapy by 808 nm laser irradiation. HNT@Fe3O4@PPy@DOX shows the ability of T2-weighted magnetic resonance imaging, which could be considered as a promising application in magnetic targeting tumor therapy. In vitro and in vivo experiments demonstrate that HNTs nanoplatform has good biocompatibility and produces a strong antitumor effect trigged by near-infrared laser irradiation. The novel chemo-photothermal therapy nanoplatform based on HNTs may be developed as a multifunctional nanoparticle for imaging and therapy in breast cancer.

Graphene Oxide Composite for Selective Recognition, Capturing, Photothermal Killing of Bacteria over Mammalian Cells.

The multifunctional photothermal therapy (PTT) platform with the ability to selectively kill bacteria over mammalian cells has received widespread attention recently. Herein, we prepared graphene oxide-amino(polyethyleneglycol) (GO-PEG-NH2) while using the hydrophobic interaction between heptadecyl end groups of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethyleneglycol)] (DSPE-PEG-NH2) and graphene oxide (GO). Based on GO-PEG-NH2, the versatile PTT system was constructed with simultaneous selective recognition, capturing, and photothermal killing of bacteria. When the cells undergo bacterial infection, owing to the poly(ethylene glycol) (PEG) chains and positively charged amino groups, GO-PEG-NH2 can specifically recognize and capture bacteria in the presence of cells. Meanwhile, the stable photothermal performance of GO-PEG-NH2 enables the captured bacteria to be efficiently photothermally ablated upon the irradiation of 808 nm laser. Besides, the GO-PEG-NH2 is highly stable in various biological media and it exhibits low cytotoxicity, suggesting that it holds great promise for biological applications. This work provides new insight into graphene-based materials as a PTT agent for the development of new therapeutic platforms.

Alginate mediated functional aggregation of gold nanoclusters for systemic photothermal therapy and efficient renal clearance

For renal clearable nanoagents, it is challenging to delay the renal clearance to acquire efficient tumor accumulation. Herein, we report sodium alginate (SA) stabilized gold (Au) NCs. The Au NCs are of high biocompatibility and renal clearable. Contributed from the ligands of SA, the half-life (t1/2) of Au NCs is prolonged to ∼9.3 h, enhancing the tumor accumulation rate to 10.4 %ID/g. In tumor microenvironment (TME), the Au NCs are stimulated to functionally aggregate, which switches on the photothermal effect. Animal experiments prove that Au NCs aggregates are efficient photothermal therapy (PTT) agents for both local treatment of single tumors and systemic treatment of double-tumor models without causing noticeable side effects, confirming the biosecurity of Au NCs and systemic PTT. The switchable strategy of PTT may signify the establishment of a new systemic therapeutic methodology.

Effective Renal Clearance and Photothermal Therapy of a Cyclodextrin-Modified Quaterrylene Derivative.

Metabolic clearance of drugs from the body is a key element for future clinical applications. Compared with the liver-bile metabolic route, the renal-urinary route is the most desirable and efficient clearance pathway for practical use in clinical trials and can effectively decrease the long-term risk of unpredictable intracellular catabolism and the potential toxicity to normal organs. However, renal clearable photothermal therapy (PTT) agents were limited. In this paper, a permethyl-β-cyclodextrin-modified quaterrylene bisimide derivative (QDI-CD) was developed. QDI-CD as a biocompatible molecule could effectively be cleared with the renal clearance efficiency of (67.00 ± 2.37)% at 24 h by the renal-urinary route when administered by tail vein injection. Importantly, the structure of QDI-CD in urine after metabolism does not change. Furthermore, QDI-CD, as a potent photoacoustic and photothermal agent, could effectively be enriched in tumor tissue after 4 h of injection and showed the effective PTT in mice. This work developed a potent organic PTT agent with good renal clearance from the body and with promise for future clinical applications.

A Single Molecule Drug Targeting Photosensitizer for Enhanced Breast Cancer Photothermal Therapy.

Targeting is one of the most important strategies for enhancing the efficacy of cancer photothermal therapy (PTT) and reducing damage to surrounding normal tissues. Compared with the traditional targeting approaches, the active targeting of breast cancer cells in PTT using chemotherapeutic drugs, such as tamoxifen (TAM), in combination with single-molecule photothermal photosensitizers has superior selectivity and therapeutic effects. However, single-molecule drug-targeting photosensitizers for improved PTT efficacy are not widely reported. Accordingly, herein, a near-infrared induced small-molecule photothermal photosensitizer (CyT) is developed that actively targets the estrogen receptors (ERs) of breast cancer cells as well as targets mitochondria by structure-inherent targeting. Cell uptake and cytotoxicity studies using different types of cells show that CyT enhances the efficiency of TAM-based PTT by targeting ER-overexpressing breast cancer cells and selectively killing them. In vivo experiments demonstrate that CyT can be used as a photothermal agent for fluorescence imaging-guided PTT. More importantly, the intravenous injection of CyT results in better targeting and efficiency of tumor inhibition compared with that achieved with the TAM-free control molecule Cy. Thus, the study presents an excellent small-molecule photothermal agent for breast cancer therapy with potential clinical application prospects.

In\xa0situ supramolecular polymerization-enhanced self-assembly of polymer vesicles for highly efficient photothermal therapy

Vesicular photothermal therapy agents (PTAs) are highly desirable in photothermal therapy (PTT) for their excellent light-harvesting ability and versatile hollow compartments. However, up to now, the reported vesicular PTAs are generally self-assembled from small molecules like liposomes, and polymer vesicles have seldom been used as PTAs due to the unsatisfactory photothermal conversion efficiency resulting from the irregular packing of chromophores in the vesicle membranes. Here we report a nano-sized polymer vesicle from hyperbranched polyporphyrins with favorable photothermal stability and extraordinarily high photothermal efficiency (44.1%), showing great potential in imaging-guided PTT for tumors through in vitro and in vivo experiments. These excellent properties are attributed to the in situ supramolecular polymerization of porphyrin units inside the vesicle membrane into well-organized 1D monofilaments driven by π–π stacking. We believe the supramolecular polymerization-enhanced self-assembly process reported here will shed a new light on the design of supramolecular materials with new structures and functions.

Conductive adhesive self-healing nanocomposite hydrogel wound dressing for photothermal therapy of infected full-thickness skin wounds

Bacteria-infected wounds and antibiotics abuse have become significant burdens to patients and medical systems. Thus, designing a non-antibiotic-dependent multifunctional wound dressing for treating bacteria-infected wounds is urgently desired. Herein, a series of conductive self-healing and adhesive nanocomposite hydrogels with a remarkable photothermal antibacterial property based on N-carboxyethyl chitosan (CEC) and benzaldehyde-terminated Pluronic F127/carbon nanotubes (PF127/CNT) were developed, and their great potential as agents for photothermal therapy (PTT) of infected wounds was demonstrated in vivo. The hydrogels exhibited a suitable gelation time, stable mechanical properties, hemostatic properties, high water absorbency, and good biodegradability. After loading the antibiotic moxifloxacin hydrochloride, the hydrogels showed a pH-responsive release profile and good antibacterial activity. The tissue adhesive property of the hydrogels allowed them to have a good hemostatic effect in a mouse liver trauma model, mouse liver incision model, and mouse tale amputation model. The addition of CNTs endowed the hydrogel with in vitro/in vivo photothermal antimicrobial activity and good conductivity. An in vivo experiment in a mouse full-thickness skin wound-infected model indicated that the hydrogels had an excellent treatment effect leading to significantly enhanced wound closure healing, collagen deposition, and angiogenesis. In summary, these conductive photothermal self-healing nanocomposite hydrogels as multifunctional wound dressing exhibit great potential for the treatment of infected wounds.

Lanthanide-Based Nanocomposites for Photothermal Therapy under Near-Infrared Laser: Relationship between Light and Heat, Biostability, and Reaction Temperature.

In this research, typical organic/inorganic photothermal therapy (PTT) agents were designed with a combination of upconversion luminescent (UCL) or near-infrared (NIR) II imaging rare-earth nanomaterials for photo-acoustic (PA)/UCL/NIR II imaging-guided PTT under NIR laser irradiation. The results show the following: (1) The PTT effect mainly comes from NIR absorption and partly from UCL light conversion. (2) Visible UCL emission is mainly quenched by NIR absorption of the coated PTT agent and partly quenched by visible absorption, indicating that excitation may play a more important role than in the UCL emission process. (3) The biostability of the composite might be decided by the synthesis reaction temperature. Among the five inorganic/organic nanocomposites, UCNP@MnO2 is the most suitable candidate for cancer diagnosis and treatment because of its stimuli-response ability to the micro-acid environment of tumor cells and highest biostability. The composites generate heat for PTT after entering the tumor cells, and then, the visible light emission gradually regains as MnO2 is reduced to colorless Mn2+ ions, thereby illuminating the cancer cells after the therapy.

Fe-Doped Polyoxometalate as Acid-Aggregated Nanoplatform for NIR-II Photothermal-Enhanced Chemodynamic Therapy.

The combination of reactive oxygen species-involved chemodynamic therapy (CDT) and photothermal therapy (PTT) holds great promise in enhancing anticancer effects. Herein, a multifunctional Fe-doped polyoxometalate (Fe-POM) cluster is fabricated via a simple method. The Fe-POM can not only be utilized as PTT agents to generate a hyperthermia effect for cancer cell killing under near-infrared (NIR) II laser (1060 nm) irradiation, but also can be used as CDT agents to convert endogenous less-reactive H2 O2 into harmful ·OH and simultaneously deplete glutathione for an amplified CDT effect. Notably, the hyperthermia induced by PTT can further enhance the CDT effect, achieving a synergistic PTT/CDT effect. Owing to the self-assembling properties at lowered pH values, the Fe-POM exhibits high tumor accumulation as revealed by photoacoustic imaging. More importantly, Fe-POM enables effective destruction of tumors without inducing noticeable damage to normal tissues under 1060 nm laser irradiation. The work presents a new type of multifunctional agent with high PTT/CDT efficacy, providing promising methods for PTT-enhanced CDT in a NIR-II biowindow.

Biocompatible AuPd@PVP core-shell nanoparticles for enhancement of radiosensitivity and photothermal cancer therapy

Nanostructures have been studied and applied in many fields for their outstanding properties. On account of the similar dimensions to the biomolecules, smart designed nanostructures are the rising materials in biotechnology and medical engineering. Our work reported the reduction method to synthesize AuPd@PVP nanoparticles (NPs) in the presence of polyvinyl pyrrolidone (PVP), which act as both surfactant and stabilizing agent. The existence of PVP shell guarantees the good biocompatibility both in vivo and in vitro, and makes it easy to modify on the surface. The combination takes both advantages of Au and Pd. The absorption region is broadened while enhancing the photothermal conversion ability, that makes AuPd@PVP NPs excellent photothermal therapy (PTT) agent under NIR laser irradiation of lower power. Meanwhile, the NPs also contribute to radiotherapy (RT) as the sensitizer. Combination and cooperation of PTT and RT make it more efficient for cancer therapy. Thus, the excellent features of photothermal conversion, radiosensitivity, and biocompatibility, signify the immense potential of AuPd@PVP NPs for application in tumor treatment.

Multi-stimuli responsive mesoporous silica-coated carbon nanoparticles for chemo-photothermal therapy of tumor

In this work, a traceable dual-porous mesoporous silica-coated mesoporous carbon nanocomposite (MCN@Si) with high drug loading capacity and high photothermal conversion efficiency (30.5 %) was successfully prepared. Based on the nanocomposite, a pH/redox/near infrared (NIR) multi-stimuli responsive drug delivery system was constructed to realize the accurate drug delivery, drug controlled release and chemo-photothermal synergistic antitumor therapy. MCN@Si was used as a vehicle to load doxorubicin (DOX) with a high drug loading efficacy of 48.2 % and a NIR absorbance agent for photothermal therapy and NIR thermal imaging. Carbon dots (CDs) with proper size were covalently attached to the surface of MCN@Si via disulfide bonds to block the mesopores, preventing DOX premature release from DOX/MCN@Si-CDs. Besides, CDs were served as fluorescent probe to prove the visualization potential of the drug delivery system. DOX was rapidly released at the condition of low pH and high GSH concentration due to the breakage of disulfide bonds and protonation of DOX. Moreover, the local hyperthermia generated by MCN@Si-CDs under NIR irradiation could not only directly kill cells, but also accelerate DOX release and enhance cells sensitivity and permeability. Two-dimensional cells and three-dimensional tumor spheroids assays illustrated that DOX/MCN@Si-CDs + NIR group exhibited a superior thermochemotherapy synergistic treatment effect and the combination index (CI) was 0.378. Biodistribution study showed the biosecurity of preparations and its prolonged detention time in tumor sites. Besides, antitumor experiment in vivo also performed the excellent synergistic inhibition effect. All the results demonstrated that DOX/MCN@Si-CDs is a traceable multi-stimuli responsive nanodelivery system and can achieve efficient chemo-photothermal synergistic antitumor therapy.

Gold-coated iron oxide nanoparticles as a potential photothermal therapy agent to enhance eradication of breast cancer cells

Iron oxide nanoparticles (Fe3O4 NPs) possess unique physicochemical properties which make them great for biomedical applications. This study reports the development of gold (Au) coated Fe3O4 (Au-Fe3O4 NPs) for photothermal therapy to eradicate breast cancer cells (MCF-7). The spherical shape of monodisperse Au-Fe3O4 NPs with an average size of 20.8 nm was confirmed by TEM. The cell viability evaluation of Au-Fe3O4 NPs showed negligible toxicity toward MCF-7 cells after 24 h. Significant cell reduction was observed for MCF-7 (73.9%) cells following photothermal therapy at highest concentration of NPs (50 μgFe/ml) for 10 minutes illumination when compared with other intervention groups. It can be concluded that, the synthesized Au-Fe3O4 NPs is an effective and promising photothermal therapy agent for breast cancer treatment.

Algae Extraction Controllable Delamination of Vanadium Carbide Nanosheets with Enhanced Near-Infrared Photothermal Performance.

The two-dimensional (2D) vanadium carbide (V2 C) MXene has shown great potential as a photothermal agent (PTA) for photothermal therapy (PTT). However, the use of V2 C in PTT is limited by the harsh synthesis condition and low photothermal conversion efficiency (PTCE). Herein, we report a completely different green delamination method using algae extraction to intercalate and delaminate V2 AlC to produce mass V2 C nanosheets (NSs) with a high yield (90 %). The resulting V2 C NSs demonstrated good structural integrity and remarkably high absorption in near infrared (NIR) region with a PTCE as high as 48 %. Systemic in vitro and in vivo studies demonstrate that the V2 C NSs can serve as efficient PTA for photoacoustic (PA) and magnetic resonance imaging (MRI)-guided PTT of cancer. This work provides a cost-effective, environment-friendly, and high-yielding disassembly approach of MAX, opening a new avenue to develop MXenes with desirable properties for a myriad of applications.

Algae Extraction Controllable Delamination of Vanadium Carbide Nanosheets with Enhanced Near‐Infrared Photothermal Performance

AbstractThe two‐dimensional (2D) vanadium carbide (V2C) MXene has shown great potential as a photothermal agent (PTA) for photothermal therapy (PTT). However, the use of V2C in PTT is limited by the harsh synthesis condition and low photothermal conversion efficiency (PTCE). Herein, we report a completely different green delamination method using algae extraction to intercalate and delaminate V2AlC to produce mass V2C nanosheets (NSs) with a high yield (90 %). The resulting V2C NSs demonstrated good structural integrity and remarkably high absorption in near infrared (NIR) region with a PTCE as high as 48 %. Systemic in vitro and in vivo studies demonstrate that the V2C NSs can serve as efficient PTA for photoacoustic (PA) and magnetic resonance imaging (MRI)‐guided PTT of cancer. This work provides a cost‐effective, environment‐friendly, and high‐yielding disassembly approach of MAX, opening a new avenue to develop MXenes with desirable properties for a myriad of applications.

Folin-Ciocalteu Assay Inspired Polyoxometalate Nanoclusters as a Renal Clearable Agent for Non-Inflammatory Photothermal Cancer Therapy.

Similar to translated thermal ablative techniques in clinic, the occurrence of cellular necrosis during tumor photothermal therapy (PTT) would induce inflammatory responses that are detrimental to therapeutic outcomes. Inspired by the well-known colorimetric Folin-Ciocalteu assay, monodispersed and renal-clearable tungsten (W)-based polyoxometalate nanoclusters (W-POM NCs, average diameter of around 2.0 nm) were successfully obtained here through a facile redox reaction with natural gallic acid in alkaline aqueous solution. Apart from excellent stability in the form of freeze-dried powder, the as-prepared W-POM NCs occupied considerable biocompatibility toward normal cells/tissues both in vitro and in vivo, since no obvious toxicities were observed by treating female Balb/c mice with concentrated W-POM NCs during the 30 day post-treatment period. More importantly, W-POM NCs exhibited not only considerable near-infrared (NIR) light absorption (coloration effect originated from the existence of electron-trapped W5+) for efficient PTT but also impressive anti-inflammatory ability (eliminating inflammation-related reactive oxygen species by the oxidation of W5+ into W6+ state) to achieve better therapeutic outcomes. Thus, our study pioneers the application of POMs for non-inflammatory PTT with expected safety and efficiency.

Treating Acute Kidney Injury with Antioxidative Black Phosphorus Nanosheets.

Black phosphorus nanosheets (BPNSs) have been actively employed as nanomedicine agents for photothermal and photodynamic therapy by virtue of their unique optical properties. However, their chemical reactivity as a competent biomaterial has not been fully explored yet. Here, we report on the use of BPNSs as reactive oxygen species (ROS) scavengers to cure acute kidney injury (AKI) in mice. Importantly, in vivo analysis in mice revealed that BPNSs were preferably accumulated in kidney. We found that BPNSs alleviated oxidative-pressure-induced cellular apoptosis. In a ROS-triggered acute kidney injury (AKI) model, BPNSs effectively consumed ROS in kidney, demonstrating high efficacy for curing AKI. BPNSs also exhibited excellent biocompatibility and biodegradability, making them promising candidates for therapeutic treatment of AKI and other renal diseases.

Indocyanine Green-Nexturastat A-PLGA Nanoparticles Combine Photothermal and Epigenetic Therapy for Melanoma.

In this study, we describe poly (lactic-co-glycolic) acid (PLGA)-based nanoparticles that combine photothermal therapy (PTT) with epigenetic therapy for melanoma. Specifically, we co-encapsulated indocyanine green (ICG), a PTT agent, and Nexturastat A (NextA), an epigenetic drug within PLGA nanoparticles (ICG-NextA-PLGA; INAPs). We hypothesized that combining PTT with epigenetic therapy elicits favorable cytotoxic and immunomodulatory responses that result in improved survival in melanoma-bearing mice. We utilized a nanoemulsion synthesis scheme to co-encapsulate ICG and NextA within stable and monodispersed INAPs. The INAPs exhibited concentration-dependent and near-infrared (NIR) laser power-dependent photothermal heating characteristics, and functioned as effective single-use agents for PTT of melanoma cells in vitro. The INAPs functioned as effective epigenetic therapy agents by inhibiting the expression of pan-histone deacetylase (HDAC) and HDAC6-specific activity in melanoma cells in vitro. When used for both PTT and epigenetic therapy in vitro, the INAPs increased the expression of co-stimulatory molecules and major histocompatibility complex (MHC) Class I in melanoma cells relative to controls. These advantages persisted in vivo in a syngeneic murine model of melanoma, where the combination therapy slowed tumor progression and improved median survival. These findings demonstrate the potential of INAPs as agents of PTT and epigenetic therapy for melanoma.

Dual-Targeted Phototherapeutic Agents as Magic Bullets for Cancer.

Imagine the ideal cancer drug that only kills cancer cells and does not affect nearby noncancerous cells. In the words of Paul Ehrlich, the drug acts like a magic bullet. This Topical Review summarizes an emerging new strategy to achieve this audacious goal. The central concept is a dual-targeted phototherapeutic agent for photodynamic or photothermal therapy. The dual-targeted phototherapeutic agent promotes cancer cell specificity by leveraging three levels of selectivity. Cell death will only occur in the anatomical location that is illuminated with light (Selectivity Level 1) and in cancer cells within the illumination area that have selectively accumulated the agent (Selectivity Level 2). The cancer cell killing effect is highly localized if the agent accumulates in hypersensitive intracellular organelles (Selectivity Level 3). The common targeting units for cancer cells and organelles are described, along with recent examples of dual-targeted phototherapeutic agents that incorporate these two classes of targeting units.