Effective Photothermal Therapy Agents Research Articles

Hybrid Au-star@Prussian blue for high-performance towards bimodal imaging and photothermal treatment

In recent years, branched or star-shaped Au nanostructures composed of core and protruding arms have attracted much attention due to their unique optical properties and morphology. As the clinically adapted nanoagent, prussian blue (PB) has recently gained widespread attention in cancer theranostics with potential applications in magnetic resonance (MR) imaging. In this article, we propose a hybrid star gold nanostructure（Au-star@PB）as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI)/ photoacoustic imaging（PAI） and photothermal therapy (PTT) of tumors. Importantly, the Au-star@PB nanoparticles function as effective MRI/PA contrast agents in vivo by increasing T1-weighted MR/PAI signal intensity and as effective PTT agents in vivo by decreasing the tumor volume in MCF-7 tumor bearing BALB / c mouse model as well as in vitro by lessening tumor cells growth rate. Interestingly, we found the main photothermal effect of Au-star@PB is derived from Au-star, but not PB. In summary, the hybrid structure of Au-star@PB NPs with good biological safety, significant photostability, dual imaging capability, and high therapeutic efficiency, might offer a novel avenue for the future diagnosis and treatment of cancer.

Rapid Tumor Targeting of Renal-Clearable ZW800-1 Conjugate for Efficient Photothermal Cancer Therapy.

The combination of near-infrared (NIR) fluorophores and photothermal therapy (PTT) provides a new opportunity for safe and effective cancer treatment. However, the precise molecular design of functional NIR fluorophores with desired properties, such as high tumor targetability and low nonspecific uptake, remains challenging. In this study, a renal-clearable NIR fluorophore conjugate with high tumor targetability was developed for efficient photothermal cancer therapy. The isoniazid (INH)–ZW800-1 conjugate (INH–ZW) was synthesized by conjugating an antibiotic drug, INH, with a well-known zwitterionic NIR fluorophore, ZW800-1, to improve in vivo performance and fluorescence-guided cancer phototherapy. INH–ZW not only showed rapid tumor accumulation without nonspecific tissue/organ uptake within 1 h after the injection but also generated thermal energy to induce cancer cell death under NIR laser irradiation. Compared with previously reported ZW800-1 conjugates, INH–ZW preserved the ideal biodistribution of ZW800-1 and facilitated improved tumor targeting and PTT. Together, these results demonstrate that the INH–ZW conjugate has great potential to serve as an effective PTT agent capable of rapid tumor targeting and high renal clearance, with excellent photothermal efficacy.

Noble Metal Nanomaterials for NIR-Triggered Photothermal Therapy in Cancer.

It is of great significance to develop anticancer therapeutic agents or technologies with high degree of specificity and patient compliance, while low toxicity. The emerging photothermal therapy (PTT) has become a new and powerful therapeutic technology due to its noninvasiveness, high specificity, low side effects to normal tissues and strong anticancer efficacy. Noble metal nanomaterials possess strong surface plasmon resonance (SPR) effect and synthetic tunability, which make them facile and effective PTT agents with superior optical and photothermal characteristics, such as high absorption cross-section, incomparable optical-thermal conversion efficiency in the near infrared (NIR) region, as well as the potential of bioimaging. By incorporating with various functional reagents such as antibodies, peptides, biocompatible polymers, chemo-drug and immune factors, noble metal nanomaterials have presented strong potential in multifunctional cancer therapy. Herein, the recent development regarding the application of noble metal nanomaterials for NIR-triggered PTT in cancer treatment is summarized. A variety of studies with good therapeutic effects against cancer from impressive photothermal efficacy of noble metal nanomaterials are concluded. Intelligent nanoplatforms through ingenious fabrication showing potential of multifunctional PTT, combined with chemo-therapy, immunotherapy, photodynamic therapy (PDT), as well as simultaneous imaging modality are also demonstrated.

Interfacial Reaction-Induced Defect Engineering: Enhanced Visible and Near-Infrared Absorption of Wide Band Gap Metal Oxides with Abundant Oxygen Vacancies.

Modified metal oxides with narrow band gaps have attracted great interest in photothermal applications because of their wide optical absorption range. To tune wide band gap metal oxides into visible and near-infrared responsive materials, we deploy a unique interfacial reaction-induced defect engineering approach, which enables us to effectively modify the electronic structure of metal oxides by introducing oxygen vacancy defects. This approach reduced the band gap of zirconia from 5.47 to 1.38 eV, accompanied by a color change to black. More importantly, it is not limited by the size of the metal oxides, and bulk black zirconia was successfully obtained for the first time. It has been demonstrated that the prepared black zirconia can be applied as an effective photothermal therapy agent in vitro. Additionally, the interfacial reaction-induced defect engineering approach has been successfully extended to enhance the optical absorption of other metal oxides.

Microtubule network as a potential candidate for targeting by gold nanoparticle-assisted photothermal therapy

Photothermal therapy is achieving ever-increasing attention as a promising method for killing cancer cells. Although, gold nanoparticles are regarded as one of the most effective photothermal therapy agents, the mechanisms underlying their action have to be addressed. Moreover, studies have showed that gold nanoparticles induce apoptosis in treated cultures. Hence, in this study, we investigated the interaction of folic acid functionalized gold nanoparticles and gold-shelled Fe3O4 nanoparticles with microtubule and microtubule associated protein tau in order to introduce intracellular targets of these nanoparticles and provide a holistic view about the mechanism of action of gold nanoparticles used in photothermal therapy. Various spectroscopic methods were used to find gold nanoparticles interaction with Tubulin and Tau. Our results indicated that these gold nanoparticles interact with both Tau and Tubulin and their affinity increases as temperature rises. Also, the results illustrated that quenching mechanism for gold nanoparticles interaction with Tubulin and Tau was static. The hydrophobic interaction was determined as driving force for gold nanoparticles binding to Tubulin and Tau. Moreover, it was showed that both type of gold nanoparticles stabilize microtubule polymers. These results suggest Tau and Tubulin as intracellular target of gold nanoparticles and propose that microtubule network is at the heart of apoptosis mechanisms initiated by photothermal therapy.

Assessing fluorescence detection and effective photothermal therapy of near-infrared polymer nanoparticles using alginate tissue phantoms.

Photothermal therapy (PTT) uses light absorbing materials to generate heat for treatment of diseases, like cancer. The advantages of using PTT components that absorb in the near-infrared (NIR) include reduced tissue auto-fluorescence and higher penetration depths. However, NIR laser light can still be scattered and absorbed by biological tissues, thus decreasing the amount of the energy reaching the PTT agents. We have developed two distinct formulations of NIR-absorbing nanoparticles, one which can be utilized for PTT only, and another for both PTT and fluorescence imaging of colorectal cancer. In this work, the fluorescence detection limit and the PTT heating potential of the two nanoparticle types were determined using alginate tissue phantoms. The objective of this study was to determine the PTT efficiency and theranostic potential of the nanoparticles by irradiating 3D collagen tumor spheroids, containing nanoparticles and CT26 mouse colorectal cancer cells, through increasing tissue phantom thicknesses and then quantifying cell death. Materials and Methods Our lab has previously developed nanoparticles based on the semiconducting, conjugated polymer poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b']dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe). We have also made a hybrid nanoparticle that heats and fluoresces by combining PCPDTBSe polymer with the fluorescent poly[(9,9-dihexylfluorene)-co-2,1,3-benzothiadiazole-co-4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole] (PFBTDBT10) polymer to yield nanoparticles termed Hybrid Donor-Acceptor Polymer Particles (H-DAPPs). H-DAPPs and PCPDTBSe nanoparticles were added to three-dimensional collagen gel tumor spheroids in order to represent nanoparticles in a tumor. Alginate tissue phantoms, comprised of an optical scattering agent (Intralipid) and an optical absorbing material (hemoglobin) in order to mirror biological tissue scattering effects, were used to simulate increasing tissue thickness between the nanoparticles and the PTT energy source. Fluorescence from the H-DAPPs was detectable through 6 mm of tissue phantoms. It was found that less than 10% of the laser energy could penetrate through 9 mm of tissue phantoms and only 60% of the laser energy passed through the 1.5 mm phantoms, regardless of laser power. PTT experiments, using 800 nm light at 2.2 W/cm2 for 60 s through tissue phantoms to stimulate nanoparticle-doped tumor spheroids, showed 55% cell death through 3 mm of tissue phantoms using H-DAPPs. Results from using the PCPDTBSe nanoparticles showed 72% cell death through 3 mm and over 50% cell death through 6 mm of tissue phantoms. The results of this work validated the heating potential and fluorescence detection limitations of two theranostic polymer nanoparticles by utilizing alginate tissue phantoms and 3D tumor spheroids. H-DAPPs and PCPDTBSe polymer nanoparticles can be utilized as effective PTT agents by exploiting their absorption of NIR light and H-DAPPs have advantageous fluorescence for imaging colorectal cancer. The data generated from this study design can allow for other NIR absorbing and fluorescing nanoparticle formulations to be evaluated prior to in vivo experimentation. Lasers Surg. Med. 50:1040-1049, 2018. © 2018 Wiley Periodicals, Inc.

Preparation of vapreotide-templated silver nanocages and their photothermal therapy efficacy

Abstract Vapreotide acetate (Vap) was used as a biotemplate to synthesize silver nanocages through direct co-incubation of a AgNO 3 solution, following by reduction using fresh NaBH 4 . The characterized vapreotide-templated silver nanocages (Vap-AgNCs) presented a wide and red shifted absorption band with a maximum between 480 nm and 800 nm and possessed a uniform structure with a face-centered cubic crystal structure. The biocompatibility of Vap-AgNCs was assessed using the MTT method, indicating Vap-AgNCs had better biocompatibility when its concentration was lower than 2.5 × 10 − 4 mmol·L − 1 . The photothermal characteristics of Vap-AgNCs were analyzed with laser irradiation (808 nm, 1.5 W·cm − 2 ) and the results showed that the temperature of the Vap-AgNCs solution reached 45 °C starting from 25 °C within 5 min. Additionally, Vap-AgNCs with a laser led to HeLa cell death. Therefore, the prepared Vap-AgNCs is expected to be an effective photothermal therapy agent.

Composite iron oxide-Prussian blue nanoparticles for magnetically guided T1-weighted magnetic resonance imaging and photothermal therapy of tumors.

Theranostic nanoparticles offer the potential for mixing and matching disparate diagnostic and therapeutic functionalities within a single nanoparticle for the personalized treatment of diseases. In this article, we present composite iron oxide-gadolinium-containing Prussian blue nanoparticles (Fe3O4@GdPB) as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI) and photothermal therapy (PTT) of tumors. These particles combine the well-described properties and safety profiles of the constituent Fe3O4 nanoparticles and gadolinium-containing Prussian blue nanoparticles. The Fe3O4@GdPB nanoparticles function both as effective MRI contrast agents and PTT agents as determined by characterizing studies performed in vitro and retain their properties in the presence of cells. Importantly, the Fe3O4@GdPB nanoparticles function as effective MRI contrast agents in vivo by increasing signal:noise ratios in T1-weighted scans of tumors and as effective PTT agents in vivo by decreasing tumor growth rates and increasing survival in an animal model of neuroblastoma. These findings demonstrate the potential of the Fe3O4@GdPB nanoparticles to function as effective theranostic agents.

Renal Clearable Ag Nanodots for in Vivo Computer Tomography Imaging and Photothermal Therapy.

Albumin-stabilized Ag nanodots (ANDs) are prepared by a one-step biomineralization method. The highly crystallized nanodots have ultrasmall sizes (approximately 5.8 nm) and robust X-ray attenuation (5.7313 HU per mM Ag). The unlabeled ANDs are directly excreted from the body via the urine after in vivo X-ray computer tomography (CT) imaging application. ANDs could be used as CT imaging agents and effective photothermal therapy agents. Tumor growth inhibition reaches 90.2% after photothermal treatment with ANDs. ANDs are promising tools for in vivo CT imaging and clearable near-infrared-triggered theranostic agents.

Dual wavelength stimulation of polymeric nanoparticles for photothermal therapy

Photothermal therapy (PTT) has several applications in the areas of wound healing, pain management, bacterial infection control, and cancer treatment dependent on the temperature that is generated. PTT is often used exclusively with near infrared (NIR) light and most nanoparticles (NP) used for PTT are designed to absorb within one narrow range of wavelengths. We have developed a dual-wavelength photothermal therapy by capitalizing on the dual absorption of nanoparticles in the blue and NIR range. Our lab has previously developed NP based on the semiconducting, conjugated polymer poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b']dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe). The NP have strong absorption in the blue and NIR regions. In this report, we have explored the heat generated by PCPDTBSe NP using simultaneous delivery of 450 and 800 nm light, either independently or together for photothermal ablation of mouse colorectal cancer cells. The heat generation studies indicated that the use of either 450 or 800 nm wavelengths at the same fluences produced approximately the same temperature change of deionized water. Fluences of 114.6 and 229.2 J/cm2 , utilizing 450 or 800 nm light applied individually resulted in temperatures of 8-47°C above ambient temperature, leading to a 90% reduction in cell viability. Simultaneous stimulation of the PCPDTBSe NP with 450 and 800 nm light effectively doubles the effective power delivered, resulting in temperatures 18-63°C above ambient and 100% photothermal ablation of the colorectal cancer cells. The results of this study demonstrate that PCPDTBSe polymer NP can be utilized as effective PTT agents by capitalizing on their dual absorption of both blue and NIR light. Lasers Surg. Med. 48:893-902, 2016. © 2016 Wiley Periodicals, Inc.

Hydrophilic MoSe2 Nanosheets as Effective Photothermal Therapy Agents and Their Application in Smart Devices.

A facile poly(vinylpyrrolidone) (PVP)-assisted exfoliation method is utilized to simultaneously exfoliate and noncovalently modify MoSe2 nanosheets. The resultant hydrophilic nanosheets are shown to be promising candidates for biocompatible photothermal therapy (PTT) agents, and they could also be encapsulated into a hydrogel matrix for some intelligent devices. This work not only provides novel insights into exfoliation and modification of transition metal dichalcogenide (TMD) nanosheets but also might spark more research into engineering multifunctional TMD-related nanocomposites, which is in favor of further exploiting the attractive properties of these emerging layered two-dimensional (2D) nanomaterials.

Coating Carbon Nanosphere with Patchy Gold for Production of Highly Efficient Photothermal Agent.

Gold- or carbon-based photothermal therapy (PTT) agents have shown encouraging therapeutic effects of PTT in the near-infrared region (NIR) in many preclinical animal experiments. It is expected that gold/carbon hybrid nanomaterial will possess combinational NIR light absorption and can achieve further improvement in photothermal conversion efficiency. In this work, we design and construct a novel PTT agent by coating a carbon nanosphere with patchy gold. To synthesize this composite particle with Janus structure, a new versatile approach based on a facile adsorption-reduction method was presented. Different from the conventional fabrication procedures, the formation of patchy gold in this approach is mainly a thermodynamics-driven spontaneous process. The results show that when compared with the conventional PTT agent gold nanorod the obtained nanocomposites not only have higher photothermal conversion efficiency but also perform more thermally stable. On the basis of these outstanding photothermal effects, the in vitro and in vivo photothermal performances in a MCF-7 cells (human breast adenocarcinoma cell line) and mice were investigated separately. Additionally, to further illustrate the advantage of this asymmetric structure, their potential was explored by selective surface functionalization, taking advantage of the affinity of both patchy gold and carbon domain to different functional molecules. These results suggest that this new hybrid nanomaterial can be used as an effective PTT agent for cancer treatment in the future.

Activatable hyaluronic acid nanoparticle as a theranostic agent for optical/photoacoustic image-guided photothermal therapy.

Photothermal therapy (PTT) is an emerging treatment modality that is under intensive preclinical investigations for the treatment of various medical conditions, including cancer. However, the lack of targeting function of PTT agents hampers its clinical application. An effective and nontoxic delivery vehicle that can carry PTT agents into tumor areas is still needed urgently. In this study, we developed a multifunctional nanocomposite by loading copper sulfide (CuS) into Cy5.5-conjugated hyaluronic acid nanoparticles (HANP), obtaining an activatable Cy5.5-HANP/CuS (HANPC) nanocomposite. In this system, Cy5.5 fluorescent signal is quenched by CuS inside the particle until the whole nanocomposite is degraded by hyaluronidase present in tumor, giving strong fluorescence signals delineating the tumor. Importantly, CuS with strong NIR absorbance appears to be an excellent contrast agent for photoacoustic (PA) imaging and an effective PTT agent. After intravenous administration of HANPC into SCC7 tumor-bearing mice, high fluorescence and PA signals were observed in the tumor area over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.25±0.25 for optical imaging and 3.8±0.42 for PA imaging). The tumors were then irradiated with a laser, and a good tumor inhibition rate (89.74% on day 5) was observed. Our studies further encourage application of this HA-based multifunctional nanocomposite for image-guided PTT in biomedical applications, especially in cancer theranostics.