Gold nanocages in cancer diagnosis,therapy, and theranostics: A brief review

Regarding the increasing number of cancer patients, the global burden of this disease is continuing to grow. Despite a considerable improvement in the diagnosis and treatment of various types of cancer, new diagnosis and treatment strategies are required. Nanotechnology, as an interesting and advanced field in medicine, is aimed to further advance both cancer diagnosis and treatment. Gold nanocages (AuNCs), with hollow interiors and porous walls, have received a great deal of interest in various biomedical applications such as diagnosis, imaging, drug delivery, and hyperthermia therapy due to their special physicochemical characteristics including the porous structure and surface functionalization as well as optical and photothermal properties. This review is focused on recent developments in therapeutic and diagnostic and applications of AuNCs with an emphasis on their theranostic applications in cancer diseases.     

Light‐Responsive Biodegradable Nanorattles for Cancer Theranostics

Cancer nanotheranostics, integrating both diagnostic and therapeutic functions into nanoscale agents, are advanced solutions for cancer management. Herein, a light‐responsive biodegradable nanorattle‐based perfluoropentane‐(PFP)‐filled mesoporous‐silica‐film‐coated gold nanorod (GNR@SiO₂‐PFP) is strategically designed and prepared for enhanced ultrasound (US)/photoacoustic (PA) dual‐modality imaging guided photothermal therapy of melanoma. The as‐prepared nanorattles are composed of a thin mesoporous silica film as the shell, which endows the nanoplatform with flexible morphology and excellent biodegradability, as well as large cavity for PFP filling. Upon 808 nm laser irradiation, the loaded PFP will undergo a liquid–gas phase transition due to the heat generation from GNRs, thus generating nanobubbles followed by the coalescence into microbubbles. The conversion of nanobubbles to microbubbles can improve the intratumoral permeation and retention in nonmicrovascular tissue, as well as enhance the tumor‐targeted US imaging signals. This nanotheranostic platform exhibits excellent biocompatibility and biodegradability, distinct gas bubbling phenomenon, good US/PA imaging contrast, and remarkable photothermal efficiency. The results demonstrate that the GNR@SiO₂‐PFP nanorattles hold great potential for cancer nanotheranostics.     

Rational Design of Conjugated Small Molecules for Superior Photothermal Theranostics in the NIR-II Biowindow

Extensive recent progress has been made on the design and applications of organic photothermal agents for biomedical applications because of their excellent biocompatibility comparing with inorganic materials. One major hurdle for the further development and applications of organic photothermal agents is the rarity of high-performance materials in the second near-infrared (NIR-II) window, which allows deep tissue penetration and causes minimized side effects. Up till now, there have been few reported NIR-II-active photothermal agents and their photothermal conversion efficiencies are relatively low. Herein, optical absorption of π-conjugated small molecules from the first NIR window to the NIR-II window is precisely regulated by molecular surgery of substituting an individual atom. With this technique, the first demonstration of a conjugated oligomer (IR-SS) with an absorption peak beyond 1000 nm is presented, and its nanoparticle achieves a record-high photothermal conversion efficiency of 77% under 1064 nm excitation. The nanoparticles show a good photoacoustic response, photothermal therapeutic efficacy, and biocompatibility in vitro and in vivo. This work develops a strategy to boost the light-harvesting efficiency in the NIR-II window for cancer theranostics, offering an important step forward in advancing the design and application of NIR-II photothermal agents.     

Activatable Semiconducting Theranostics: Simultaneous Generation and Ratiometric Photoacoustic Imaging of Reactive Oxygen Species In Vivo

Enhancing the generation of reactive oxygen species (ROS) is an effective anticancer strategy. However, it is a great challenge to control the production and to image ROS in vivo, both of which are vital for improving the efficacy and accuracy of cancer therapy. Herein, an activatable semiconducting theranostic nanoparticle (NP) platform is developed that can simultaneously enhance ROS generation while self‐monitoring its levels through ratiometric photoacoustic (PA) imaging. The NP platform can further guide in vivo therapeutic effect in tumors. The theranostic NP platform is composed of: (i) cisplatin prodrug and ferric ion catalyst for ROS generation, a part of combination cancer therapy; and (ii) a ratiometric PA imaging nanoprobe consisting of inert semiconducting perylene‐diimide (PDI) and ROS activatable near‐infrared dye (IR790s), used in ratiometric PA imaging of ROS during cancer treatment. Ratiometric PA signals are measured at two near‐infrared excitation wavelengths: 680 and 790 nm for PDI and IR790s, respectively. The measurements show highly accurate visualization of ^?OH generation in vivo. This novel ROS responsive organic theranostic NP allows not only synergistic cancer chemotherapy but also real‐time monitoring of the therapeutic effect through ratiometric PA imaging.     

A PIID-DTBT based semi-conducting polymer dots with broad and strong optical absorption in the visible-light region: Highly effective contrast agents for multiscale and multi-spectral photoacoustic imaging

As a hybrid imaging technique, photoacoustic imaging (PAI) can provide multiscale morphological information of tissues, and the use of multi-spectral PAI (MSPAI) can recover the spatial distribution of chromophores of interest, such as hemoglobin within tissues. Herein, we developed a contrast agent that can very effectively combine multiscale PAI with MSPAI for a more comprehensive characterization of complex biological tissues. Specifically, we developed novel PIID-DTBT based semi-conducting polymer dots (Pdots) that show broad and strong optical absorption in the visible-light region (500–700 nm). The performances of gold nanoparticles (GNPs) and gold nanorods (GNRs), which have been verified as excellent photoacoustic contrast agents, were compared with that of the Pdots based on the multiscale PAI system. Both ex vivo and in vivo experiments demonstrated that the Pdots have better photoacoustic conversion efficiency at 532 nm than GNPs and showed similar photoacoustic performance with GNRs at 700 nm at the same mass concentration. Photostability and toxicity tests demonstrated that the Pdots are photostable and biocompatible. More importantly, an in vivo MSPAI experiment indicated that the Pdots have better photoacoustic performance than the blood and therefore the signals can be accurately extracted from the background of vascular-rich tissues. Our work demonstrates the great potential of Pdots as highly effective contrast agents for the precise localization of lesions relative to the blood vessels based on multiscale PAI and MSPAI.

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The Nanoassembly of an Intrinsically Cytotoxic Near‐Infrared Dye for Multifunctionally Synergistic Theranostics

The combination of diagnostic and therapeutic functions in a single theranostic nanoagent generally requires the integration of multi‐ingredients. Herein, a cytotoxic near‐infrared (NIR) dye (IR‐797) and its nanoassembly are reported for multifunctional cancer theranostics. The hydrophobic IR‐797 molecules are self‐assembled into nanoparticles, which are further modified with an amphiphilic polymer (C18PMH‐PEG5000) on the surface. The prepared PEG‐IR‐797 nanoparticles (PEG‐IR‐797 NPs) possess inherent cytotoxicity from the IR‐797 dye and work as a chemotherapeutic drug which induces apoptosis of cancer cells. The IR‐797 NPs are found to have an ultrahigh mass extinction coefficient (444.3 L g^?1 cm^?1 at 797 nm and 385.9 L g^?1 cm^?1 at 808 nm) beyond all reported organic nanomaterials (<40 L g^?1 cm^?1) for superior photothermal therapy (PTT). In addition, IR‐797 shows some aggregation‐induced‐emission (AIE) properties. Combining the merits of good NIR absorption, high photothermal energy conversion efficiency, and AIE, makes the PEG‐IR‐797 NPs useful for multimodal NIR AIE fluorescence, photoacoustic, and thermal imaging‐guided therapy. The research exhibits the possibility of using a single ingredient and entity to perform multimodal NIR fluorescence, photoacoustic, and thermal imaging‐guided chemo‐/photothermal combination therapy, which may trigger wide interest from the fields of nanomedicine and medicinal chemistry to explore multifunctional theranostic organic molecules.     

Targeted blue nanoparticles as photoacoustic contrast agent for brain tumor delineation

Distinguishing a tumor from non-neoplastic tissue is a challenging task during cancer surgery. Several attempts have been made to use visible or fluorescent agents to aid in the visualization of a tumor during surgery. We describe a novel method to delineate brain tumors, using a highly sensitive photoacoustic imaging technique that is enhanced by tumor-targeting blue nanoparticles serving as a contrast agent. Experiments on phantoms and on rat brains, ex vivo, demonstrate the high sensitivity of photoacoustic imaging in delineating tumors containing contrast agent at a concentration much lower than needed for visualization by the naked eye. The limit of detection of the system for the nanoparticles is about 0.77 μg/mL in water (equivalent to 0.84 μmol/L Coomassie Blue dye). The present exploratory study suggests that photoacoustic imaging, when used with strongly optical absorbing contrast agents, could facilitate cancer surgery intraoperatively by revealing the distribution and extent of the tumor.      

正弦脉冲激光激发声波的热膨胀机制理论

阐述了激光与液体媒质作用通过热膨胀机制激发平面光声源的理论;针对激光脉冲为正弦波形的情况,求解出δ脉冲和长脉冲分别在约束界面和自由界面下产生声脉冲的解析解,通过仿真得到了声脉冲剖面,并对每种情况下产生的声波进行了对比分析;然后对液体中激光致声的光声转换效率进行了理论研究,对正弦波形δ脉冲和长脉冲激光分别在约束界面和自由界面下产生声脉冲的光声转换效率分别进行了理论分析和仿真,并讨论了液体媒质特性参数和激光参数对转换效率的影响,提出了提高转换效率的方案。     

Single‐Photomolecular Nanotheranostics for Synergetic Near‐Infrared Fluorescence and Photoacoustic Imaging‐Guided Highly Effective Photothermal Ablation

Multi‐modality imaging‐guided cancer therapy is considered as a powerful theranostic platform enabling simultaneous precise diagnosis and treatment of cancer. However, recently reported multifunctional systems with multiple components and sophisticate structures remain major obstacles for further clinical translation. In this work, a single‐photomolecular theranostic nanoplatform is fabricated via a facile nanoprecipitation strategy. By encapsulating a semiconductor oligomer (IT‐S) into an amphiphilic lipid, water‐dispersible IT‐S nanoparticles (IT‐S NPs) are prepared. The obtained IT‐S NPs have a very simple construction and possess ultra‐stable near‐infrared (NIR) fluorescence (FL)/photoacoustic (PA) dual‐modal imaging and high photothermal conversion efficiency of 72.3%. Accurate spatiotemporal distribution profiles of IT‐S NPs are successfully visualized by NIR FL/PA dual‐modal imaging. With the comprehensive in vivo imaging information provided by IT‐S NPs, tumor photothermal ablation is readily realized under precise manipulation of laser irradiation, which greatly improves the therapeutic efficacy without any obvious side effects. Therefore, the IT‐S NPs allow high tumor therapeutic efficacy under the precise guidance of FL/PA imaging techniques and thus hold great potential as an effective theranostic platform for future clinical applications.     

PEGylated Tantalum Nanoparticles: A Metallic Photoacoustic Contrast Agent for Multiwavelength Imaging of Tumors

Elemental tantalum is a well‐known biomedical metal in clinics due to its extremely high biocompatibility, which is superior to that of other biomedical metallic materials. Hence, it is of significance to expand the scope of biomedical applications of tantalum. Herein, it is reported that tantalum nanoparticles (Ta NPs), upon surface modification with polyethylene glycol (PEG) molecules via a silane‐coupling approach, are employed as a metallic photoacoustic (PA) contrast agent for multiwavelength imaging of tumors. By virtue of the broad optical absorbance from the visible to near‐infrared region and high photothermal conversion efficiency (27.9%), PEGylated Ta NPs depict high multiwavelength contrast capability for enhancing PA imaging to satisfy the various demands (penetration depth, background noise, etc.) of clinical diagnosis as needed. Particularly, the PA intensity of the tumor region postinjection is greatly increased by 4.87, 7.47, and 6.87‐fold than that of preinjection under 680, 808, and 970 nm laser irradiation, respectively. In addition, Ta NPs with negligible cytotoxicity are capable of eliminating undesirable reactive oxygen species, ensuring the safety for biomedical applications. This work introduces a silane‐coupling strategy for the surface engineering of Ta NPs, and highlights the potential of Ta NPs as a biocompatible metallic contrast agent for multiwavelength photoacoustic image.     

Nebulized Gadolinium‐Based Nanoparticles: A Theranostic Approach for Lung Tumor Imaging and Radiosensitization

Lung cancer is the most common and most fatal cancer worldwide. Thus, improving early diagnosis and therapy is necessary. Previously, gadolinium‐based ultra‐small rigid platforms (USRPs) were developed to serve as multimodal imaging probes and as radiosensitizing agents. In addition, it was demonstrated that USRPs can be detected in the lungs using ultrashort echo‐time magnetic resonance imaging (UTE‐MRI) and fluorescence imaging after intrapulmonary administration in healthy animals. The goal of the present study is to evaluate their theranostic properties in mice with bioluminescent orthotopic lung cancer, after intrapulmonary nebulization or conventional intravenous administration. It is found that lung tumors can be detected non‐invasively using fluorescence tomography or UTE‐MRI after nebulization of USRPs, and this is confirmed by histological analysis of the lung sections. The deposition of USRPs around the tumor nodules is sufficient to generate a radiosensitizing effect when the mice are subjected to a single dose of 10 Gy conventional radiation one day after inhalation (mean survival time of 112 days versus 77 days for irradiated mice without USRPs treatment). No apparent systemic toxicity or induction of inflammation is observed. These results demonstrate the theranostic properties of USRPs for the multimodal detection of lung tumors and improved radiotherapy after nebulization.     

Co-Al spinel-based nanoparticles synthesized by flame spray pyrolysis for glycerol conversion

The catalytic properties of Co-Al spinel nanoparticles prepared by liquid-feed flame spray pyrolysis (L-F FSP) were investigated in the glycerol conversion in gas phase in an atmosphere of hydrogen. Reduction at 1123?K of the as-synthesized spinel nanoparticles induced the formation a new phase containing metallic cobalt species. Although, the reducibility of cobalt oxides is greatly decreased due to interaction with aluminium species, this strong interaction may prevent the aggregation of Co particles under the harsh reduction conditions. X-ray photoelectron spectroscopy (XPS) of the reduced spinel nanoparticles at 1123?K revealed that the Co/Al atomic ratio has decreased to Co/Al?=?0.11, which may indicate a redistribution of the aluminum and cobalt species at the surface of the sample submitted to the reduction in a flow of hydrogen at 1123?K. X-ray diffraction (XRD) and high resolution electron microscopy (HRTEM) also reinforced the formation of metallic cobalt species after reduction of cobalt from the spinel nanoparticles at 1123?K. The main products obtained from the conversion of glycerol in the gas phase were hydroxyacetone, pyruvaldehyde, lactic acid and lactide. FSP ensured uniform dispersion of the active metal on a support material.     

Hydrophilic bismuth sulfur nanoflower superstructures with an improved photothermal efficiency for ablation of cancer cells

Nanomaterials with intense near-infrared (NIR) absorption exhibit effective photon-to-thermal energy transfer capabilities and can generate heat to ablate cancer cells, thus playing a pivotal role in photothermal cancer therapeutics. Herein, hydrophilic flower-like bismuth sulfur (Bi₂S₃) superstructures with uniform size and improved NIR absorption were controllably synthesized via a facile solvothermal procedure assisted by polyvinylpyrrolidone (PVP), which could adjust the product morphology. Induced by an 808-nm laser, the as-prepared Bi₂S₃ nanoflowers exhibited much higher photothermal conversion efficiency (64.3%) than that of Bi₂S₃ nanobelts (36.5%) prepared in the absence of PVP. This can be attributed not only to the Bi₂S₃ nanoflower superstructures assembled by 3-dimensional crumpled-paper-like nanosheets serving as many laser-cavity mirrors with improved reflectivity and absorption of NIR light but also to the amorphous structures with a lower band gap. Thus, to achieve the same temperature increase, the concentration or laser power density could be greatly reduced when using Bi₂S₃ nanoflowers compared to when using Bi₂S₃ nanobelts, which makes them more favorable for use in therapy due to decreased toxicity. Furthermore, these Bi₂S₃ nanoflowers effectively achieved photothermal ablation of cancer cells in vitro and in vivo. These results not only supported the Bi₂S₃ nanoflowers as a promising photothermal agent for cancer therapy but also paved an approach to exploit new agents with improved photothermal efficiency.

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