基于金纳米棒的生物检测、细胞成像和癌症的光热治疗

由于金纳米棒颗粒独特的可调的表面等离子共振特性,使得金纳米棒颗粒在纳米复合材料和功能化纳米器件的构建、纳米生物技术、生物医学等领域具有广泛而重要的应用前景。本文综述了金纳米棒颗粒的生物检测、细胞成像和癌症的光热治疗方面的最新研究进展,并介绍了金纳米棒颗粒的光学性质和金纳米棒颗粒和几种主要的表面修饰方法,对金纳米棒颗粒在生物应用过程中存在的主要问题进行了讨论。     

Gold Nanorod–Photosensitizer Complex Obtained by Layer‐by‐Layer Method for Photodynamic/Photothermal Therapy In Vitro

Gold nanorod (GNR)–photosensitizer (PS) complex was prepared using anionic PS (sodium salt of purpurin‐18) and cationic poly(allylamine hydrochloride) by layer‐by‐layer method, and was characterized by transmission electron microscopy, UV‐vis spectroscopy, and zeta potential. The GNR–PS complex is a promising agent for synergistic (photothermal and photodynamic) therapy (PTT/PDT), in which PTT generates heat as well as operates the PS release which maximize the following PDT activity. The combined dual therapy, PTT followed by PDT, exhibits a significantly higher photocytotoxicity result based on synergistic effect of hyperthermia from PTT as well as singlet oxygen photogeneration from PDT.     

Thiol-Responsive Gold Nanodot Swarm with Glycol Chitosan for Photothermal Cancer Therapy

Photothermal therapy (PTT) is one of the most promising cancer treatment methods because hyperthermal effects and immunogenic cell death via PTT are destructive to cancer. However, PTT requires photoabsorbers that absorb near-infrared (NIR) light with deeper penetration depth in the body and effectively convert light into heat. Gold nanoparticles have various unique properties which are suitable for photoabsorbers, e.g., controllable optical properties and easy surface modification. We developed gold nanodot swarms (AuNSw) by creating small gold nanoparticles (sGNPs) in the presence of hydrophobically-modified glycol chitosan. The sGNPs assembled with each other through their interaction with amine groups of glycol chitosan. AuNSw absorbed 808-nm laser and increased temperature to 55 °C. In contrast, AuNSw lost its particle structure upon exposure to thiolated molecules and did not convert NIR light into heat. In vitro studies demonstrated the photothermal effect and immunogenic cell death after PTT with AuNSW. After intratumoral injection of AuNSw with laser irradiation, tumor growth of xenograft mouse models was depressed. We found hyperthermal damage and immunogenic cell death in tumor tissues through histological and biochemical analyses. Thiol-responsive AuNSw showed feasibility for PTT, with advanced functionality in the tumor microenvironment.     

“Two‐Step” Raman Imaging Technique To Guide Chemo‐Photothermal Cancer Therapy

Graphene oxide‐wrapped gold nanorods (GO@AuNRs) offer efficient drug delivery as well as NIR laser photothermal therapy (PTT) in vitro and in vivo. However, no real‐time observation of drug release has been reported to better understand the synergy of chemotherapy and PTT. Herein, surface‐enhance Raman spectroscopy (SERS) is employed to guide chemo‐photothermal cancer therapy by a two‐step mechanism. In the presence of GO as an internal standard, SERS signals of DOX (doxorubicin) loaded onto GO@AuNRs are found to be pH‐responsive. Both DOX and GO show strong SERS signals before the DOX@GO@AuNRs are endocytic. However, when the DOX@GO@AuNRs enter acidic microenvironments such as endosomes and/or lysosomes, the DOX signals start decreasing while the GO signals remain the same. This plasmonic antenna could be used to identify the appropriate time to apply the PTT laser during chemo‐photothermal therapy.     

Luminescent Gold Nanorods To Enhance the Near-Infrared Emission of a Photosensitizer for Targeted Cancer Imaging and Dual Therapy: Experimental and Theoretical Approach

Strong plasmon absorption in the near-infrared (NIR) region renders gold nanorods (GNRs) amenable for biomedical applications, particularly for photothermal therapy. However, these nanostructures have not been explored for their imaging potential because of their weak emission profile. In this study, the weak fluorescence emission of GNRs is tuned to match that of the absorption of a photosensitizer (PS) molecule, and energy transfer from the GNR to PS enhances the emission profile of the GNR–PS combination. GNR complexes generally quench the fluorescence emission of nearby chromophores. However, herein, the complex retains or rather enhances the fluorescence through competition in energy transfer. Excitation-dependent energy transfer has been explained experimentally and theoretically by using DFT calculations, the CIE chromaticity diagram, and power spectrum. The final GNR–PS complex modified for tumor specificity serves as an excellent organ-specific theranostic probe for bioimaging and dual therapy both in vitro and in vivo. Principal component analysis designates photodynamic therapy a better candidate than that of photothermal therapy for long-term efficacy in vivo.     

Biodegradable Gold Nanovesicles with an Ultrastrong Plasmonic Coupling Effect for Photoacoustic Imaging and Photothermal Therapy

The hierarchical assembly of gold nanoparticles (GNPs) allows the localized surface plasmon resonance peaks to be engineered to the near‐infrared (NIR) region for enhanced photothermal therapy (PTT). Herein we report a novel theranostic platform based on biodegradable plasmonic gold nanovesicles for photoacoustic (PA) imaging and PTT. The disulfide bond at the terminus of a PEG‐b‐PCL block‐copolymer graft enables dense packing of GNPs during the assembly process and induces ultrastrong plasmonic coupling between adjacent GNPs. The strong NIR absorption induced by plasmon coupling and very high photothermal conversion efficiency (η=37 %) enable simultaneous thermal/PA imaging and enhanced PTT efficacy with improved clearance of the dissociated particles after the completion of PTT. The assembly of various nanocrystals with tailored optical, magnetic, and electronic properties into vesicle architectures opens new possibilities for the construction of multifunctional biodegradable platforms for biomedical applications.     

A Photoinduced Nonadiabatic Decay‐Guided Molecular Motor Triggers Effective Photothermal Conversion for Cancer Therapy

It remains highly challenging to identify small molecule‐based photothermal agents with a high photothermal conversion efficiency (PTCE). Herein, we adopt a double bond‐based molecular motor concept to develop a new class of small photothermal agents to break the current design bottleneck. As the double‐bond is twisted by strong twisted intramolecular charge transfer (TICT) upon irradiation, the excited agents can deactivate non‐radiatively through the conical intersection (CI) of internal conversion, which is called photoinduced nonadiabatic decay. Such agents possess a high PTCE of 90.0 %, facilitating low‐temperature photothermal therapy in the presence of a heat shock protein 70 inhibitor. In addition, the behavior and mechanism of NIR laser‐triggered molecular motions for generating heat through the CI pathway have been further understood through theoretical and experimental evidence, providing a design principle for highly efficient photothermal and photoacoustic agents.     

Temperature‐Correlated Afterglow of a Semiconducting Polymer Nanococktail for Imaging‐Guided Photothermal Therapy

Nanoparticles for photothermal therapy: Real‐time temperature monitoring is critical to reduce the nonspecific damage during photothermal therapy (PTT); however, PTT agents that can emit temperature‐related signals are rare and limited to few inorganic nanoparticles. We herein synthesize a semiconducting polymer nanococktail (SPN_CT) that can not only convert photo‐energy to heat but also emit temperature‐correlated luminescence after cessation of light excitation. Such an afterglow luminescence of the SPN_CT detects tumors more sensitively than fluorescence as a result of the elimination of tissue autofluorescence, while its temperature‐dependent nature allows tumor temperature to be optically monitored under near‐infrared (NIR) laser irradiation. Thus, SPN_CT represents the first organic optical nanosystem that enables optical‐imaging guided PTT without real‐time light excitation.     

肿瘤靶向Pt-Cu基纳米平台用于近红外二区光声成像引导的光热治疗

基于层层（LBL）自组装技术,在Pt-Cu纳米合金表面依次包覆带正电的聚赖氨酸（PLL）和带负电的透明质酸（HA）,成功构筑Pt-Cu@PLL@HA纳米平台。HA不仅延长了纳米平台血液循环时间,还可实现肿瘤主动靶向作用,提升肿瘤部位富集效果。在肿瘤区域透明质酸酶（HAase）作用下HA快速降解,释放Pt-Cu@PLL （+）颗粒,有利于肿瘤细胞特异性摄取。基于Pt-Cu合金良好的近红外二区（NIR-Ⅱ）吸收性能,实现了NIR-Ⅱ光声成像引导的NIR-Ⅱ光热高效抗肿瘤效果。     

Linker‐free Gold Nanoparticle Superstructure Coated with Poly(dopamine) by Site‐Specific Polymerization for Amplifying Photothermal Cancer Therapy

Although linker‐free Au nanoparticle superstructures (AuNPSTs) have demonstrated to have satisfactory photothermal conversion efficiency owing to their enhanced visible‐near‐infrared absorption caused by the interparticle coupling, they cannot be used directly for in vivo photothermal therapy (PTT) of cancer because of poor stability. To address this issue, we herein propose a polymer‐coating strategy, dressing AuNPST on a poly(dopamine) (PDA) coat, and successfully investigate the in vivo PTT effect of AuNPSTs. By employing Triton X‐100 as an emulsifier for the formation of AuNPSTs, dopamine was site‐specifically polymerized around each AuNPST by the interaction between ?OH of Triton X‐100 and ?NH₂ of dopamine. As‐fabricated AuNPST/PDA has a sphere‐like shape with an average diameter of ～106 nm and the PDA shell is about 10 nm PDA thick. The AuNPST/PDA shows enhanced durability to heat, acid, and alkali compared with bare AuNPST. Also, under 808 nm laser irradiation, AuNPST/PDA shows photothermal conversion efficiency of ～33%, higher than bare AuNPST (～23%). Significantly, AuNPST/PDA can be used as in‐vitro and in‐vivo PTT agent and shows excellent therapeutic efficacy for tumor ablation thanks to its enhanced stability and biocompatibility, indicative of its potential practicability in clinical PTT.     

Simultaneous Application of Photothermal Therapy and an Anti‐inflammatory Prodrug using Pyrene–Aspirin‐Loaded Gold Nanorod Graphitic Nanocapsules

Photothermal therapy (PTT) has been extensively developed as an effective approach against cancer. However, PTT can trigger inflammatory responses, in turn simulating tumor regeneration and hindering subsequent therapy. A therapeutic strategy was developed to deliver enhanced PTT and simultaneously inhibit PTT‐induced inflammatory response. 1‐Pyrene methanol was utilize to synthesize the anti‐inflammatory prodrug pyrene–aspirin (P‐aspirin) with a cleavable ester bond and also facilitate loading the prodrug on gold nanorod (AuNR)‐encapsulated graphitic nanocapsule (AuNR@G), a photothermal agent, through π–π interactions. Such AuNR@G‐P‐aspirin complexes were used for near‐infrared laser‐triggered photothermal ablation of solid tumor and simultaneous inhibition of PTT‐induced inflammation through the release of aspirin in tumor milieu. This strategy showed excellent effects in vitro and in vivo.     

Gold Nanoparticles Grown on Ionic Liquid‐Functionalized Single‐Walled Carbon Nanotubes: New Materials for Photothermal Therapy

Gold nanoparticles were grown on single‐walled carbon nanotubes (SWNTs) coated with a thiol‐functionalized ionic liquid resulting in the formation of core‐shell structures referred to as SWNT‐IL‐Au nanohybrid materials. The nanohybrid materials were characterized by high‐resolution transmission electron microscopy (HR‐TEM), Raman‐, and UV/Vis absorption spectroscopy. The nanohybrid materials were found to enter lysosomes in HeLa cells and show negligible cytotoxicity. Interestingly, they have an enhanced NIR absorption that is effectively transferred into heat to cause localized hyperthermia, resulting in rapid cell death; overall, the material appears to have excellent properties for photothermal therapeutic applications.     

Magnetic Nanohybrids Loaded with Bimetal Core–Shell–Shell Nanorods for Bacteria Capture,Separation, and Near‐Infrared Photothermal Treatment

A novel antimicrobial nanohybrid based on near‐infrared (NIR) photothermal conversion is designed for bacteria capture, separation, and sterilization (killing). Positively charged magnetic reduced graphene oxide with modification by polyethylenimine (rGO–Fe₃O₄–PEI) is prepared and then loaded with core–shell–shell Au–Ag–Au nanorods to construct the nanohybrid rGO–Fe₃O₄–Au–Ag–Au. NIR laser irradiation melts the outer Au shell and exposes the inner Ag shell, which facilitates controlled release of the silver shell. The nanohybrids combine physical photothermal sterilization as a result of the outer Au shell with the antibacterial effect of the inner Ag shell. In addition, the nanohybrid exhibits high heat conductivity because of the rGO and rapid magnetic‐separation capability that is attributable to Fe₃O₄. The nanohybrid provides a significant improvement of bactericidal efficiency with respect to bare Au–Ag–Au nanorods and facilitates the isolation of bacteria from sample matrixes. A concentration of 25 μg mL^?1 of nanohybrid causes 100 % capture and separation of Escherichia coli O157:H7 (1×10⁸ cfu mL^?1) from an aqueous medium in 10 min. In addition, it causes a 22 °C temperature rise for the surrounding solution under NIR irradiation (785 nm, 50 mW cm^?2) for 10 min. With magnetic separation, 30 μg mL^?1 of nanohybrid results in a 100 % killing rate for E. coli O157:H7 cells. The facile bacteria separation and photothermal sterilization is potentially feasible for environmental and/or clinical treatment.     

Phase‐Transition Induced Conversion into a Photothermal Material: Quasi‐Metallic WO2.9 Nanorods for Solar Water Evaporation and Anticancer Photothermal Therapy

Phase transition from WO₃ to sub‐stoichiometric WO_2.9 by a facile method has varied the typical semiconductor to be quasi‐metallic with a narrowed band gap and a shifted Femi energy to the conduction band, while maintaining a high crystallinity. The resultant WO_2.9 nanorods possess a high total absorption capacity (ca. 90.6 %) over the whole solar spectrum as well as significant photothermal conversion capability, affording a conversion efficiency as high as around 86.9 % and a water evaporation efficiency of about 81 % upon solar light irradiation. Meanwhile, the promising potential of the nanorods for anticancer photothermal therapy have been also demonstrated, with a high photothermal conversion efficiency (ca. 44.9 %) upon single wavelength near‐infrared irradiation and a high tumor inhibition rate (ca. 98.5 %). This study may have opened up a feasible route to produce high‐performance photothermal materials from well‐developed oxides.     

Near‐Infrared‐Activated Nanocalorifiers in Microcapsules: Vapor Bubble Generation for In Vivo Enhanced Cancer Therapy

Photothermal therapy based on gold nanostructures has been widely investigated as a state‐of‐the‐art noninvasive therapy approach. Because single nanoparticles cannot harvest sufficient energy, self‐assemblies of small plasmonic particles into large aggregates are required for enhanced photothermal performance. Self‐assembled gold nanorods in lipid bilayer‐modified microcapsules are shown to localize at tumor sites, generate vapor bubbles under near‐infrared light exposure, and subsequently damage tumor tissues. The polyelectrolyte multilayer enables dense packing of gold nanorods during the assembly process, which leads to the formation of vapor bubbles around the excited capsules. The resulting vapor bubbles achieve a high efficiency of suppressing tumor growth compared to single gold nanorods. In vivo experiments demonstrated the ability of soft‐polymer multilayer microcapsules to cross the biological barriers of the body and localize at target tissues.