纳米光热材料在抗菌领域的研究进展

耐药菌的出现极大提高了临床发病率及死亡率,并对人们的生活及医疗系统造成了很大的冲击。耐药菌的快速变异和新抗生素研发的滞后,迫切需要新的抗菌手段以应对上述问题。光热疗法（PTT）是一种将太阳能转换成热能（光热转换）,提高局部温度,进而杀死细菌的新型抗菌技术。PTT具有独特的抗菌机制,产生耐药菌的可能性较低,在抗菌领域具有独特的优势。各种具有光热转换效果的纳米粒子以及基于此设计的纳米复合材料是PTT的关键。该文综述了近年来光热剂（PTAs）在抗菌领域的研究进展,总结了PTAs的种类及应用领域,对PTT抗菌发展存在的问题进行了分析,对未来研究的重点和方向进行了展望,以期对PTAs抗菌材料的研究提供新的思路。     

Organic Semiconductors for Photothermal Therapy and Photoacoustic Imaging

In recent years, semiconducting polymer nanoparticles (SPNs) have been attracting considerable attention because of their outstanding characteristics such as higher light and thermal stability. They are widely used in fields of biomedicine such as photoacoustic (PA) imaging (PAI), photodynamic therapy (PDT), and photothermal therapy (PTT). PAI, a new imaging modality based on PA effects, shows great promise in biomedical applications. SPNs that display strong optical absorbance in the visible and near-infrared (NIR) regions can be promising candidates for in vivo PTT and PAI. Here we introduce the preparation of organic conjugated polymer fluorescent nanoparticles in the aqueous phase. We then discuss the application of water-dispersible conjugated polymer nanoparticles in PA and PTT. Finally, we discuss the opportunities and challenges for the development of organic conjugated polymer nanoparticles.     

Photodynamic Therapy of Up-Conversion Nanomaterial Doped with Gold Nanoparticles

Two key concerns exist in contemporary cancer chemotherapy: limited therapeutic efficiency and substantial side effects in patients. In recent years, researchers have been investigating the revolutionary cancer treatment techniques of photodynamic therapy (PDT) and photothermal therapy (PTT) proposed by many scholars. A photothermal treatment of cancer was synthesized using the hydrothermal method which has high photothermal conversion efficiency and can generate reactive oxygen species (ROS) in cells. Photothermal treatment of tumors has a good short-term effect and photodynamic therapy lasts longer. However, both PTT and PDT have their inevitable shortcomings and it is difficult to completely eradicate a tumor using a single mode of treatment. PTT and PDT synergistic treatment not only inherits the advantages of low toxicity and side effects of phototherapy but also enables the two treatment methods to complement each other. It is an effective strategy to improve curative effects and reduce toxic and side effects. Furthermore, gold doped UCNPs have an exceptionally high target recognition for tumor cells. The gold doped UCNPs, in particular, are non-toxic to normal tissues, endowing the as-prepared medications with outstanding therapeutic efficacy and exceptionally low side effects. These findings may encourage the creation of fresh, effective imaging-guided approaches to meet the goal of photothermal cancer therapy.     

Progress of Nanomaterials-Based Photothermal Therapy for Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is one of the top 15 most prevalent cancers worldwide. However, the current treatment models for OSCC (e.g., surgery, chemotherapy, radiotherapy, and combination therapy) present several limitations: damage to adjacent healthy tissue, possible recurrence, low efficiency, and severe side effects. In this context, nanomaterial-based photothermal therapy (PTT) has attracted extensive research attention. This paper reviews the latest progress in the application of biological nanomaterials for PTT in OSCC. We divide photothermal nanomaterials into four categories (noble metal nanomaterials, carbon-based nanomaterials, metal compounds, and organic nanomaterials) and introduce each category in detail. We also mention in detail the drug delivery systems for PTT of OSCC and briefly summarize the applications of hydrogels, liposomes, and micelles. Finally, we note the challenges faced by the clinical application of PTT nanomaterials and the possibility of further improvement, providing direction for the future research of PTT in OSCC treatment.     

Melanin-Like Nanomedicine in Photothermal Therapy Applications

Photothermal therapy (PTT) mediated by nanomaterial has become an attractive tumor treatment method due to its obvious advantages. Among various nanomaterials, melanin-like nanoparticles with nature biocompatibility and photothermal conversion properties have attracted more and more attention. Melanin is a natural biological macromolecule widely distributed in the body and displays many fascinating physicochemical properties such as excellent biocompatibility and prominent photothermal conversion ability. Due to the similar properties, Melanin-like nanoparticles have been extensively studied and become promising candidates for clinical application. In this review, we give a comprehensive introduction to the recent advancements of melanin-like nanoparticles in the field of photothermal therapy in the past decade. In this review, the synthesis pathway, internal mechanism and basic physical and chemical properties of melanin-like nanomaterials are systematically classified and evaluated. It also summarizes the application of melanin-like nanoparticles in bioimaging and tumor photothermal therapy (PTT)in detail and discussed the challenges they faced in clinical translation rationally. Overall, melanin-like nanoparticles still have significant room for development in the field of biomedicine and are expected to applied in clinical PTT in the future.     

Tumor Targeting with Methotrexate-Conjugated Zwitterionic Near-Infrared Fluorophore for Precise Photothermal Therapy

Targeted tumor imaging can effectively enable image-guided surgery and precise cancer therapy. Finding the right combination of anticancer drugs and near-infrared (NIR) fluorophores is the key to targeted photothermal cancer treatment. In this study, a tumor-targetable NIR fluorophore conjugate with rapid body clearance was developed for accurate tumor imaging and effective photothermal therapy (PTT). The methotrexate (MTX) and zwitterionic NIR fluorophore conjugate (MTX-ZW) were prepared by conjugating a folate antagonist MTX with an aminated ZW800-1 analog to increase the tumor targetability for NIR laser-based PTT of cancer. The MTX, known as a poor tumor-selective drug, showed high tumor accumulation and rapid background clearance after conjugation with the highly water-soluble zwitterionic NIR fluorophore up to 4 h post-injection. The photothermal energy was generated from the MTX-ZW conjugate to induce necrotic cell death in the targeted tumor site under 808 nm laser irradiation. Compared with the previously reported MTX conjugates, the MTX-ZW conjugate can be a great candidate for targeted tumor imaging and fluorescence-guided photothermal cancer therapy. Therefore, these results provide a strategy for the design of drug-fluorophore conjugates and elaborate therapeutic platforms for cancer phototherapy.     

Assessing the Efficiency of Triangular Gold Nanoparticles as NIR Photothermal Agents In Vitro and Melanoma Tumor Model

Photothermal therapy (PTT) is gaining a lot of interest as a cancer treatment option with minimal side effects due to the efficient photothermal agents employed. They are based on nanomaterials that, upon laser irradiation, absorb photon energy and convert it into heat to induce hyperthermia, which destroys the cancer cells. Here, the unique light-to-heat conversion features of three different gold nanotriangular nanoparticles (AuNTs) are evaluated with respect to their absorption properties to select the most efficient nanoheater with the highest potential to operate as an efficient photothermal agent. AuNTs with LSPR response in- and out- of resonance with the 785 nm near-infrared (NIR) excitation wavelength are investigated. Upon 15 min laser exposure, the AuNTs that exhibit a plasmonic response in resonance with the 785 nm laser line show the highest photothermal conversion efficacy of 80%, which correlates with a temperature increase of 22 °C. These photothermal properties are well-preserved in agarose-based skin biological phantoms that mimic the melanoma tumoral tissue and surrounding healthy tissue. Finally, in vitro studies on B16.F10 melanoma cells prove by fluorescence staining and MTT assay that the highest phototoxic effect after NIR laser exposure is induced by AuNTs with LSPR response in resonance with the employed laser line, thus demonstrating their potential implementation as efficient photothermal agents in PTT.     

Multifunctional Cyanine-Based Theranostic Probe for Cancer Imaging and Therapy

Cancer is one of the leading causes of death in the world. A cancer-targeted multifunctional probe labeled with the radionuclide has been developed to provide multi-modalities for NIR fluorescence and nuclear imaging (PET, SPECT), for photothermal therapy (PTT), and targeted radionuclide therapy of cancer. In this study, synthesis, characterization, in vitro, and in vivo biological evaluation of the cyanine-based probe (DOTA-NIR790) were demonstrated. The use of cyanine dyes for the selective accumulation of cancer cells were used to achieve the characteristics of tumor markers. Therefore, all kinds of organ tumors can be targeted for diagnosis and treatment. The DOTA-NIR790 labeled with lutetium-111 could detect original or metastatic tumors by using SPECT imaging and quantify tumor accumulation. The β-emission of ¹⁷⁷Lu-DOTA-NIR790 can be used for targeted radionuclide therapy of tumors. The DOTA-NIR790 enabled imaging by NIR fluorescence and by nuclear imaging (SPECT) to monitor in real-time the tumor accumulation and the situation of cancer therapy, and to guide the surgery or the photothermal therapy of the tumor. The radionuclide-labeled heptamethine cyanine based probe (DOTA-NIR790) offers multifunctional modalities for imaging and therapies of cancer.     

Transdermal Photothermal Sterilization and Abscess Elimination Research of BSA-CuS Nanoparticles in vivo

The treatment of subcutaneous abscess caused by drug-resistant bacteria is facing great difficulties and receiving more attention. In this work, we employed BSA-CuS nanoparticles as a photothermal reagent to apply photothermal therapy (PTT) to combat drug-resistant bacteria in vitro and subcutaneous abscess in vivo. The BSA-CuS nanoparticles were found to be stable and biocompatible without cytotoxicity toward NIH3T3 and 4T1 cells. In vitro experiments showed that three species of drug-resistant pathogens, including Escherichia coli, Staphylococcus aureus, and Candida albicans, could be effectively sterilized under co-incubation with BSA-CuS nanoparticles and then irradiation with 1064 nm NIR laser via tissue penetration. BSA-CuS nanoparticles together with 1064 nm NIR laser irradiation could also effectively diminish subcutaneous abscesses caused by drug-resistant bacteria on mice under PTT and depth PTT without causing any serious side effects and organic damage in vivo.That is OK, thank you!     

Dual‐Responsive Carbon Dot for pH/Redox‐Triggered Fluorescence Imaging with Controllable Photothermal Ablation Therapy of Cancer

Herein we describe fluorescence resonance energy transfer (FRET) for a pH/redox‐activatable fluorescent carbon dot (FNP) to realize “off–on” switched imaging‐guided controllable photothermal therapy (PTT). The FNP is a carbonized self‐crosslinked polymer that allows IR825 loading (FNP[IR825]) via hydrophobic interactions for cancer therapy. Fluorescence bioimaging was achieved by the internalization of FNP(IR825) into tumor cells, wherein glutathione (GSH) disulfide bonds are reduced, and benzoic imine groups are cleaved under acidic conditions. The release of IR825 from the FNP core in this system may be used to efficiently control PTT‐mediated cancer therapy via its photothermal conversion after near‐infrared (NIR) irradiation. In vitro and in vivo cellular uptake studies revealed efficient uptake of FNP(IR825) by tumor cells to treat the disease site. In this way we demonstrated in mice that our smart nanocarrier can effectively kill tumor cells under exposure to a NIR laser, and that the particles are biocompatible with various organs. This platform responds sensitively to the exogenous environment inside the cancer cells and may selectively induce the release of PTT‐mediated cytotoxicity. Furthermore, this platform may be useful for monitoring the elimination of cancer cells through the fluorescence on/off switch, which can be used for various applications in the field of cancer cell therapy and diagnosis.     

Tumor Targeting by Conjugation of Chlorambucil with Zwitterionic Near-Infrared Fluorophore for Cancer Phototherapy

Improving the tumor targeting of anticancer drugs to minimize systemic exposure remains challenging. The chemical conjugation of anticancer drugs with various near-infrared (NIR) fluorophores may provide an effective approach to improve NIR laser-induced cancer phototherapy. Towards this end, the selection of NIR fluorophores conjugated with hydrophobic anticancer drugs is an important consideration for targeted cancer photothermal therapy (PTT). In this study, a highly water-soluble zwitterionic NIR fluorophore (ZW800) was prepared to conjugate with a water-insoluble anticancer drug, chlorambucil (CLB), to improve tumor targeting, in vivo biodistribution, and PTT performance. The in vivo results using an HT-29 xenograft mouse model demonstrated that the CLB-ZW800 conjugate not only exhibited high tumor accumulation within 4 h after injection, but also showed rapid body clearance behavior for less systemic toxicity. Furthermore, the tumor tissue targeted by the CLB-ZW800 conjugate was exposed to 808 nm NIR laser irradiation to generate photothermal energy and promote apoptotic cell death for the effective PTT of cancer. Therefore, this study provides a feasible strategy for developing bifunctional PTT agents capable of tumor-targeted imaging and phototherapy by the conjugation of small molecule drugs with the versatile zwitterionic NIR fluorophore.     

Photothermal Effect and Multi-Modality Imaging of Up-Conversion Nanomaterial Doped with Gold Nanoparticles

Two key concerns exist in contemporary cancer chemotherapy in clinics: limited therapeutic efficiency and substantial side effects in patients. In recent years, researchers have been investigating revolutionary cancer treatment techniques and photo-thermal therapy (PTT) has been proposed by many scholars. A drug for photothermal cancer treatment was synthesized using the hydrothermal method, which has a high light-to-heat conversion efficiency. It may also be utilized as a clear multi-modality bioimaging platform for photoacoustic imaging (PAI), computed tomography (CT), and magnetic resonance imaging (MRI). When compared to single-modality imaging, multi-modality imaging delivers far more thorough and precise details for cancer diagnosis. Furthermore, gold-doped upconverting nanoparticles (UCNPs) have an exceptionally high target recognition for tumor cells. The gold-doped UCNPs, in particular, are non-toxic to normal tissues, endowing the as-prepared medications with outstanding therapeutic efficacy but exceptionally low side effects. These findings may encourage the creation of fresh effective imaging-guided approaches to meet the goal of photothermal cancer therapy.     

Functionalized Reduced Graphene Oxide as a Versatile Tool for Cancer Therapy

Cancer is one of the deadliest diseases in human history with extremely poor prognosis. Although many traditional therapeutic modalities—such as surgery, chemotherapy, and radiation therapy—have proved to be successful in inhibiting the growth of tumor cells, their side effects may vastly limited the actual benefits and patient acceptance. In this context, a nanomedicine approach for cancer therapy using functionalized nanomaterial has been gaining ground recently. Considering the ability to carry various anticancer drugs and to act as a photothermal agent, the use of carbon-based nanomaterials for cancer therapy has advanced rapidly. Within those nanomaterials, reduced graphene oxide (rGO), a graphene family 2D carbon nanomaterial, emerged as a good candidate for cancer photothermal therapy due to its excellent photothermal conversion in the near infrared range, large specific surface area for drug loading, as well as functional groups for functionalization with molecules such as photosensitizers, siRNA, ligands, etc. By unique design, multifunctional nanosystems could be designed based on rGO, which are endowed with promising temperature/pH-dependent drug/gene delivery abilities for multimodal cancer therapy. This could be further augmented by additional advantages offered by functionalized rGO, such as high biocompatibility, targeted delivery, and enhanced photothermal effects. Herewith, we first provide an overview of the most effective reducing agents for rGO synthesis via chemical reduction. This was followed by in-depth review of application of functionalized rGO in different cancer treatment modalities such as chemotherapy, photothermal therapy and/or photodynamic therapy, gene therapy, chemotherapy/phototherapy, and photothermal/immunotherapy.     

Near‐infrared‐active and pH‐responsive fluorescent polymer‐integrated hybrid graphene oxide nanoparticles for the detection and treatment of cancer

Hybrid nanoparticles for theragnosis have great potentiality to bring desire functionalities in one integrated system. The development of bioimaging guided photothermal therapy (PTT) is pivotal in optimizing cytotoxic cancer therapy. We report near‐infrared (NIR)‐active and pH‐responsive fluorescent, catechol‐conjugated, reduced graphene oxide (rGO)‐anchored hybrid nanoparticles that can sharply increase the photothermal heat in response to NIR exposure and exhibit pH‐dependent fluorescence emission for the detection of tumor areas without causing cell toxicity. The optoelectronic absorption property of poly(3,4‐ethylenedioxythiophene) [PEDOT]:dopamine‐conjugated poly(4‐styrenesulfonate‐co‐maleic acid) [D‐PSM] and 3′,4′‐dihydroxyacetophenone/boron‐dipyrromethene [CCDP/BODIPY]‐quaternized polyethylene glycol grafted poly(dimethylaminoethyl methacrylate) (C/B‐PgP) present in this hybrid nanoparticles resulted in efficient photothermal conversion with pH‐tunable fluorescence that exerted sufficient photothermal cytotoxicity to cancer cells. The in vitro cellular uptake was measured by confocal laser scanning microscopy, allowing the therapeutic efficiency and bioimaging effects to be explored. We expect that the broad optical absorption property of PEDOT:D‐PSM with BODIPY‐conjugated polymers on rGO sheets would get tremendous attraction in this enormous rising PTT with cancer detectable biomarker. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43791.     

An Engineered Nanocomplex with Photodynamic and Photothermal Synergistic Properties for Cancer Treatment

Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising therapeutic methods for cancer treatment; however, as single modality therapies, either PDT or PTT is still limited in its success rate. A dual application of both PDT and PTT, in a combined protocol, has gained immense interest. In this study, gold nanoparticles (AuNPs) were conjugated with a PDT agent, meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer, designed as nanotherapeutic agents that can activate a dual photodynamic/photothermal therapy in SH-SY5Y human neuroblastoma cells. The AuNP-mTHPC complex is biocompatible, soluble, and photostable. PDT efficiency is high because of immediate reactive oxygen species (ROS) production upon mTHPC activation by the 650-nm laser, which decreased mitochondrial membrane potential (^∆ψ_m). Likewise, the AuNP-mTHPC complex is used as a photoabsorbing (PTA) agent for PTT, due to efficient plasmon absorption and excellent photothermal conversion characteristics of AuNPs under laser irradiation at 532 nm. Under the laser irradiation of a PDT/PTT combination, a twofold phototoxicity outcome follows, compared to PDT-only or PTT-only treatment. This indicates that PDT and PTT have synergistic effects together as a combined therapeutic method. Our study aimed at applying the AuNP-mTHPC approach as a potential treatment of cancer in the biomedical field.     

Light-Triggered Covalent Coupling of Gold Nanoparticles for Photothermal Cancer Therapy

Manipulating the cross-coupling of gold nanoparticles (AuNPs) to maximize the photothermal effect is a promising strategy for cancer therapy. Here, by taking advantage of the well-known tetrazole/alkene photoclick chemistry, we have demonstrated for the first time that small AuNPs (23 nm) decorated with both 2,5-diphenyltetrazole and methacrylic acid on their surfaces can form covalently crosslinked aggregates upon laser irradiation (λ=405 nm). In vitro studies indicated that the light-triggered assembling shifted the surface plasmon resonance of AuNPs significantly to near-infrared (NIR) regions, which as a consequence effectively enhanced the efficacy of photothermal therapy for 4T1 breast cancer cells. We thus believe that this new light-triggered cross-coupling approach might offer a valuable tool for cancer treatment.     

Carbon-Based Materials in Photodynamic and Photothermal Therapies Applied to Tumor Destruction

Within phototherapy, a grand challenge in clinical cancer treatments is to develop a simple, cost-effective, and biocompatible approach to treat this disease using ultra-low doses of light. Carbon-based materials (CBM), such as graphene oxide (GO), reduced GO (r-GO), graphene quantum dots (GQDs), and carbon dots (C-DOTs), are rapidly emerging as a new class of therapeutic materials against cancer. This review summarizes the progress made in recent years regarding the applications of CBM in photodynamic (PDT) and photothermal (PTT) therapies for tumor destruction. The current understanding of the performance of modified CBM, hybrids and composites, is also addressed. This approach seeks to achieve an enhanced antitumor action by improving and modulating the properties of CBM to treat various types of cancer. Metal oxides, organic molecules, biopolymers, therapeutic drugs, among others, have been combined with CBM to treat cancer by PDT, PTT, or synergistic therapies.     

血清白蛋白-铜酞菁纳米粒子用于线粒体靶向光疗

铜酞菁是一类具有优异光物理性质和良好光热稳定性的染料,在印染、太阳能电池、传感器等领域中应用广泛。血清白蛋白作为血液中主要的转运蛋白,常用于小分子和药物的负载和运输。通过牛血清白蛋白（BSA）和铜酞菁类染料（LGS-CuPc）的自组装,构建了LGS-CuPc-BSA纳米粒子（LGS-CuPc-BSA NPs）,研究了其作为光动力和光热一体化试剂在光疗中的作用。在671 nm光照下（800 mW·cm^-2）,LGS-CuPc-BSA NPs活性氧产率达到23.3%,光热转换效率为36.8%。与LGS-CuPc比较,LGS-CuPc-BSA NPs光动力和光热治疗效果明显提升,且表现出较低的细胞毒性、良好的生物相容性以及在肿瘤细胞线粒体的定位能力,实现对肿瘤细胞的有效杀伤。     

Supramolecular Nanodrugs Based on Covalent Assembly of Therapeutic Peptides toward In Vitro Synergistic Anticancer Therapy

Therapeutic peptides have attracted significant attention in clinical applications due to their advantages in biological origination and good biocompatibility. However, the therapeutic performance of peptides is usually hindered by their short half-lives in blood and inferior activity. Herein, supramolecular nanodrugs of therapeutic peptides are constructed by covalent assembly of chemotherapeutic peptides through genipin cross-linking. The resulting nanodrugs have intense absorbance in the near-infrared region and high photothermal conversion efficiencies, leading to the possibility of photothermal therapy. The combination of photothermal therapy and chemotherapy using the nanodrugs shows synergistic therapeutic effects on cancer cells. Hence, covalent assembly not only maintains the chemotherapeutic activities of the peptides but also triggers supramolecular photothermal effects, demonstrating that the covalent assembly of therapeutic peptides through genipin cross-linking is an efficient approach in constructing supramolecular nanodrugs toward synergistic anticancer therapy.     

Biodegradable and Multifunctional Polymer Micro-Tubes for Targeting Photothermal Therapy

We describe an innovative form of polymer micro-tubes with diverse functions including biodegradation, magnetic manipulation, and photothermal effect that employs and activates photothermal therapy to target cancer cells. The micro-tube comprised soybean protein isolate, poly-l-glutamic acid, magnetite nanoparticles, plus gold nanoparticles. Through electrostatic force, these components, with opposite charges, formed pairs of layers in the pores of the template, various bilayers of soybean protein isolate and poly-l-glutamic acid served as the biodegradable building wall to each micro-tube. The layers of magnetite nanoparticle functionalized micro-tubes enabled the micro-tube manipulate to target the cancer cells by using an external magnetic field. The photo-thermal effect of the layer of gold nanoparticles on the outer surface of the micro-tubes, when under irradiation and when brought about by the near infrared radiation, elevated each sample’s temperature. In addition, and when under the exposure of the near infrared radiation, the elevated temperature of the suspension of the micro-tubes, likewise with a concentration of 0.2 mg/mL, and similarly with a power of 2 W and as well maintained for 10 min, elevated the temperature of the suspension beyond 42 °C. Such temperatures induced apoptosis of target cancer cells through the effect of photothermal therapy. The findings assert that structured micro-tubes have a promising application as a photothermal agent. From this assertion, the implications are that this multifunctional agent will significantly improve the methodology for cancer diagnosis and therapy.