有机纳米材料在肿瘤光热治疗中的应用

光热治疗是利用在近红外具有较强光吸收的材料将光能转化为热能从而杀死癌细胞,与传统的化疗、放疗相比具有副作用小、治疗特异性好的优点。近年来各种不同的纳米材料被用于肿瘤光热治疗,并在动物肿瘤模型实验中取得了令人鼓舞的治疗效果。本文重点介绍几种典型的有机纳米材料在光热治疗中的应用,并讨论这一新兴领域的发展趋势。     

一种用于肿瘤治疗的高光热转换效率和高稳定性的光热剂

基于香豆素荧光团设计合成了一种光热剂(ECEI),其光热转换效率可达 85.78%。此外,冷热循环的实验结果表明,ECEI 具有良好的光稳定性。即使在线粒体膜电位受损的情况下,ECEI 也能有效靶向线粒体,在激光照射下诱导癌细胞死亡。这使 ECEI能够最大程度地破坏线粒体,从而抑制肿瘤细胞的繁殖。对小鼠肿瘤照射 1次后,小鼠肿瘤在 10 d内逐渐消失,这表明ECEI具有良好的肿瘤抑制效果。     

一种用于肿瘤治疗的高光热转换效率和高稳定性的光热剂

基于香豆素荧光团设计合成了一种光热剂(ECEI),其光热转换效率可达 85.78%。此外,冷热循环的实验结果表明,ECEI 具有良好的光稳定性。即使在线粒体膜电位受损的情况下,ECEI 也能有效靶向线粒体,在激光照射下诱导癌细胞死亡。这使 ECEI能够最大程度地破坏线粒体,从而抑制肿瘤细胞的繁殖。对小鼠肿瘤照射 1次后,小鼠肿瘤在 10 d内逐渐消失,这表明ECEI具有良好的肿瘤抑制效果。     

Polymer materials for constructing therapeutical nanoparticles in photothermal therapy

Photothermal therapy (PTT) ablates tumors by thermal effects of photothermal agents (PTAs), and attracts wide attention due to the non-invasive characteristic. The ideal PTAs are expected to have high photothermal conversion effect under NIR irradiation, as well as targeting abilities and good biocompatibility satisfying the need of application in vivo. Nanoparticles (NPs) are commonly used as anti-tumor materials, and plenty of researches on therapeutical NPs for PTT treatment have been developed. Among various building blocks for photothermal NPs, polymer materials for biomedical applications have great advantages due to their negligible toxicity, flexibility for functional modification, and ability to integrate multiple therapeutic strategies. This review focuses on the polymer materials utilized in photothermal NP designing, including their application as excellent carriers and powerful PTAs with great PTT effects. Furthermore, the synergy therapy based on polymeric nanoplatform for enhancing PTT therapeutic efficiency will be introduced.     

D-A-D structured selenadiazolesbenzothiadiazole-based near-infrared dye for enhanced photoacoustic imaging and photothermal cancer therapy

Near-infrared (NIR) small molecular organic dyes as photothermal agents for cancer photothermal therapy (PTT) have attracted considerable research attention. Herein, two donor-acceptor-donor (D-A-D) structured NIR dyes, BBTT and SeBTT, are rationally designed, where the only difference is one heteroatom within the acceptor unit varying from sulfur to selenium (Se). More importantly, SeBTT NPs exhibit stronger NIR absorbance and higher photothermal conversion efficiency (PTCE ≈ 65.3%). In vivo experiments illustrate that SeBTT NPs can be utilized as a high contrast photoacoustic imaging (PAI) agent, and succeed in tumor suppression without noticeable damage to main organs under NIR photoirradiation. This study presents an effective molecular heteroatom surgery strategy to regulate the photothermal properties of NIR small molecules for enhanced PAI and PTT.     

PAA-derived gold nanorods for cellular targeting and photothermal therapy

A single-step LbL procedure to functionalize CTAB-capped GNRs via electrostatic self-assembly is reported. This approach allows for consistent biomolecule/GNR coupling using standard carboxyl-amine conjugation chemistry. The focus is on cancer-targeting biomolecule/GNR conjugates and selective photothermal destruction of cancer cells by GNR-mediated hyperthermia and NIR light. GNRs were conjugated to a single-chain antibody selective for colorectal carcinoma cells and used as probes to demonstrate photothermal therapy. Selective targeting and GNR uptake in antigen-expressing SW 1222 cells were observed using fluorescence microscopy. Selective photothermal therapy is demonstrated using SW 1222 cells, where >62% cell death was observed after cells are treated with targeted A33scFv-GNRs.     

Fe掺杂CuS纳米颗粒的合成及其在光热/化学动力学联合治疗中的应用

以乙酰丙酮铜和硫粉为铜源和硫源,在油酸(OA)-油胺(OM)-十八烯(ODE)体系中合成了近红外吸收的硫化铜(CuS)纳米颗粒,并通过改变硫元素活化状态的方式调节其吸收峰到适合光热治疗的1 064 nm附近。通过阳离子交换法进一步制备了Fe、Mn等元素掺杂的CuS纳米颗粒,并保持其吸收峰位置几乎不变。使用微乳法进行聚乙二醇(PEG)化修饰后,这些纳米颗粒在水溶液中表现出良好的分散性和稳定性。分别测试了CuS纳米颗粒在Fe³⁺掺杂前后的光热性能及羟基自由基(·OH)生成能力。结果表明,PEG修饰后Fe³⁺掺杂的CuS纳米颗粒(CuS∶Fe-PEG)在1 064 nm处的质量消光系数为37.5 L·g^-1·cm^-1,光热转换效率可达43.7%。虽然光热性能略低于未掺杂的CuS-PEG,但其·OH生成能力有大幅提升。细胞实验也表明,在弱酸性条件下,CuS∶Fe-PEG具有更好的肿瘤细胞抑制能力,在1 064 nm激光照射下能够有效杀死肿瘤细胞,可用于光热/化学动力学联合治疗。     

Fe掺杂CuS纳米颗粒的合成及其在光热/化学动力学联合治疗中的应用

以乙酰丙酮铜和硫粉为铜源和硫源,在油酸(OA)-油胺(OM)-十八烯(ODE)体系中合成了近红外吸收的硫化铜(CuS)纳米颗粒,并通过改变硫元素活化状态的方式调节其吸收峰到适合光热治疗的1064 nm附近。通过阳离子交换法进一步制备了Fe、Mn等元素掺杂的CuS纳米颗粒,并保持其吸收峰位置几乎不变。使用微乳法进行聚乙二醇(PEG)化修饰后,这些纳米颗粒在水溶液中表现出良好的分散性和稳定性。分别测试了CuS纳米颗粒在Fe³⁺掺杂前后的光热性能及羟基自由基(·OH)生成能力。结果表明,PEG修饰后Fe³⁺掺杂的CuS纳米颗粒(CuS∶Fe-PEG)在1064 nm处的质量消光系数为37.5 L·g^-1·cm-1,光热转换效率可达43.7%。虽然光热性能略低于未掺杂的CuS-PEG,但其·OH生成能力有大幅提升。细胞实验也表明,在弱酸性条件下,CuS∶Fe-PEG具有更好的肿瘤细胞抑制能力,在1064 nm激光照射下能够有效杀死肿瘤细胞,可用于光热/化学动力学联合治疗。     

Near infrared molybdenum oxide quantum dots with high photoluminescence and photothermal performance

The synthesized near infrared molybdenum oxide quantum dots perform excellent red fluorescence imaging performance and photothermal performance,which have 600,650 and 700 nm three unique peaks excited at 540 nm,with a high quantum yield around 20%.Meanwhile,with 808 nm NIR laser excitation,10 mg/mL modified Molybdenum oxide quantum dots can increase temperature up to 72.2℃within 150 s and 77.7℃ within 270 s,respectively.     

Highly biocompatible BSA-MnO2 nanoparticles as an efficient near-infrared photothermal agent for cancer therapy

In this work, we reported a facile, one-pot method to synthesis of bovine serum albumin (BSA)-reduced and stabilized MnO₂ nanoparticles (BSA-MnO₂ NPs) with good aqueous dispersibility and high biocompatibility. And we also showed for the first time that BSA-MnO₂ NPs displayed superior near infrared (NIR) photothermal efficiency and photostability which demonstrated as a novel class of photothermal antitumor agent.     

Controlled deposition of functionalized silica coated zinc oxide nano-assemblies at the air/water interface for blood cancer detection

We report results of the studies relating to controlled deposition of the amino-functionalized silica-coated zinc oxide (Am-Si@ZnO) nano-assemblies onto an indium tin oxide (ITO) coated glass substrate using Langmuir-Blodgett (LB) technique. The monolayers have been deposited by transferring the spread solution of Am-Si@ZnO stearic acid prepared in chloroform at the air-water interface, at optimized pressure (16 mN/m), concentration (10 mg/ml) and temperature (23 °C). The high-resolution transmission electron microscopic studies of the Am-Si@ZnO nanocomposite reveal that the nanoparticles have a microscopic structure comprising of hexagonal assemblies of ZnO with typical dimensions of 30 nm. The surface morphology of the LB multilayer observed by scanning electron microscopy shows uniform surface of the Am-Si@ZnO film in the nanometer range (<80 nm). These electrodes have been utilized for chronic myelogenous leukemia (CML) detection by covalently immobilizing the amino-terminated oligonucleotide probe sequence via glutaraldehyde as a crosslinker. The response studies of these fabricated electrodes carried out using electrochemical impedance spectroscopy show that this Am-Si@ZnO LB film based nucleic acid sensor exhibits a linear response to complementary DNA (10⁻⁶–10⁻¹⁶ M) with a detection limit of 1 × 10⁻¹⁶ M. This fabricated platform is validated with clinical samples of CML positive patients and the results demonstrate its immense potential for clinical diagnosis.     

Biocompatibility and hyperthermia cancer therapy of casein‐coated iron oxide nanoparticles in mice

Magnetic nanoparticles (MNPs) can be used as heat generation source in cancer hyperthermia therapy. While iron oxide nanoparticles (NPs) are the most popular choice for magnetic hyperthermia, adding a surface enhancement can improve its performance. Furthermore, for MNPs to be used in biomedical application their cytotoxicity needs to be evaluated. In this study biocompatibility and also in vivo performance of casein‐coated MNPs were assessed. Cell viability of normal cell lines in all of tests remained above 95% for 0.5 and 1 mg/mL concentration and even the minimum recorded cell viability for normal cell lines was 84.78% at 20 mg/mL concentration. In contrast cell viability of cancer cell lines in contact with casein coated MNPs core‐shell structure except for one sample remained below 85%. By introduction of and alternating magnetic field, cell viability of samples with lower MNP concentration dropped by 20% to 30% while this drop for samples with higher concentration was 10% to 20%. Furthermore, results of in vivo trials show that just 1 week of hyperthermia treatment with casein coated MNPs core‐shell structure can reduce the tumor size of the mice by 33%. Real‐time polymerase chain reaction results further confirmed the effectiveness of this method. Moreover, findings of this study suggest that lower injection speed can improve NPs distribution and treatment effect. Results of this study suggest that core‐shell structure can positively affect the tumor growth and the combination of good biocompatibility, innate hostility toward cancer cells and good heating power makes them a good candidate for hyperthermia cancer therapy applications.     

Small molecule nanodrugs for cancer therapy

Nanoscale drug delivery systems (DDSs) have emerged as promising candidates for cancer therapy. However, traditional nanoscale DDSs suffer from several inherent drawbacks, including sophisticated synthesis, uncontrolled structure, low drug loading capacity, high reticuloendothelial system (RES) accumulation, unpredicted metabolic mechanism, and so on. In order to solve these problems, nanodrugs self-assembled from small molecules containing anticancer drugs have received great attention in recent years. Different from traditional nanoscale DDSs, small molecule nanodrugs (SMNs) exhibit unique advantages, such as simple synthesis, defined structure, high drug loading capacity, excellent tumor accumulation and low-toxic metabolism pathway. Hence, with rational design, SMNs can achieve excellent cancer therapeutic efficacy as well as low side effects, extremely promising for the clinic translation. Up to now, significant progress has been made for the exploration of SMNs for cancer therapy. In this review, we briefly summarize the design and synthesis, biological properties, as well as their wide range of applications for cancer therapy.     

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.     

空心硫化铜负载原卟啉用于光热-声动力治疗癌细胞

制备了空心硫化铜(H-Cu_2-xS)纳米颗粒,并利用其空腔结构负载声敏剂原卟啉(PpIX)得到多功能复合纳米试剂(PpIX@H-Cu_2-xS)。H-Cu_2-xS 在近红外光(NIR)照射条件下具有良好的光热转换效果,同时具有大的比表面积(68 m²·g^-1),可实现声敏剂PpIX的高效负载。在超声(US)激发条件下(10 min),发现有46.1%的1,3-二苯基异苯并呋喃(DPBF)被PpIX@H-Cu_2-xS产生的活性氧(ROS)氧化。在体外细胞实验中,PpIX@H-Cu_2-xS 显示出良好的生物安全性,在 NIR/US 激发条件下可以高效地杀死肿瘤细胞。     

Hydrogel microfluidic co‐culture device for photothermal therapy and cancer migration

We developed the photo‐crosslinkable hydrogel microfluidic co‐culture device to study photothermal therapy and cancer cell migration. To culture MCF7 human breast carcinoma cells and metastatic U87MG human glioblastoma in the microfluidic device, we used 10 w/v% gelatin methacrylate (GelMA) hydrogels as a semi‐permeable physical barrier. We demonstrated the effect of gold nanorod on photothermal therapy of cancer cells in the microfluidic co‐culture device. Interestingly, we observed that metastatic U87MG human glioblastoma largely migrated toward vascular endothelial growth factor (VEGF)‐treated GelMA hydrogel‐embedding microchannels. The main advantage of this hydrogel microfluidic co‐culture device is to simultaneously analyze the physiological migration behaviors of two cancer cells with different physiochemical motilities and study gold nanorod‐mediated photothermal therapy effect. Therefore, this hydrogel microfluidic co‐culture device could be a potentially powerful tool for photothermal therapy and cancer cell migration applications.