pH响应型纳米药物用于化疗-光热协同治疗肿瘤

化疗协同光热治疗(PTT)是提高肿瘤疗效的一种新型治疗方式.本研究拟合成一种亚细胞器靶向的近红外响应纳米药物Fe3 O4@PDA-TPP/S2-PEG-hyd-DOX(Fe3 O4-ATSPD)作为新的光热制剂,它可通过磁靶向增强肿瘤细胞的摄取,具有良好的光热稳定性和光热转化效率.在近红外光(NlR)照射下,光热剂多巴胺(PDA)产生光热效应,促使线粒体膜电位显著下降.同时,在内涵体/溶酶体低pH值环境下,Fe3O4-ATSPD释放偶联药物DOX进入细胞核损伤DNA,最终促使肿瘤细胞凋亡.本研究制备的纳米药物能有效整合诊断和治疗,为肿瘤治疗提供新的协同治疗策略.     

可控合成空心多孔氧化硅纳米管/CuS体系应用于化疗-光热靶向治疗

多功能药物载体的设计合成并应用于肿瘤的联合治疗得到了研究人员的广泛关注.本文介绍了一种连接靶向基团的化疗-光热联合治疗纳米平台.首先制备了尺寸可控的平均长度为40、55和150 nm的空心多孔氧化硅纳米管,在表面修饰具有光热功能的硫化铜纳米颗粒,然后连接乳糖酸基团实现肝癌细胞靶向功能.平均长度为40 nm、修饰靶向基团的空心多孔材料显示出良好的生物相容性,且具有最大的HepG2细胞吞噬量.负载盐酸阿霉素的纳米复合材料表现出pH和808 nm近红外激光刺激响应的释放效果.将CuS光热治疗和盐酸阿霉素化疗相结合的方法在体外和体内的抑制肿瘤效果都优于单独治疗.研究结果表明,该纳米复合材料在化疗-光热联合治疗方面具有潜在的应用价值.     

FePS3纳米片制备及其体外光热-光动力学联合治疗性能研究

光学治疗作为一种肿瘤治疗策略具有微创、毒副作用小、治疗效率高等优势而得到广泛研究, 但单一光学治疗并不能完全消除肿瘤。新兴的二维纳米材料在光学治疗领域的优势引起了广泛关注。本研究探索了金属磷三硫族元素化合物FePS₃纳米片的制备及其多功能光学治疗性能。采用高温固相法合成FePS₃块体并通过超声协助的液相剥离法得到FePS₃纳米片, 该纳米片的平均水合粒径小于200 nm (平均153 nm), 对1064 nm激光的光热转换效率为19.7%, 且能在660 nm激光辐照下产生活性氧。细胞实验结果表明, FePS₃纳米片具有良好的光热治疗和光动力学治疗效果。因此, FePS₃纳米片可同时作为光热剂和光敏剂获得光热-光动力学联合治疗肿瘤功能, 肿瘤治疗应用潜力较大。     

纺锤状羟基氧化铁@聚吡咯复合纳米粒子的制备及其光热治疗肿瘤应用

肿瘤是世界上死亡率最高的疾病,研制新型肿瘤药物也是一项极具开发性的研究。首先制备纺锤状羟基氧化铁纳米粒子(FeOOH NPs)并作为模板,与吡咯(Py)聚合得到纺锤状羟基氧化铁@聚吡咯(FeOOH@PPy)复合纳米粒子。采用FTIR、DLS、TEM和UV-vis等测试方法对FeOOH@PPy进行了结构、性质表征,通过光热转换实验证明了该复合纳米粒子具有优异的光热转换性能,探究了复合纳米粒子的生物相容性以及肿瘤治疗中的应用潜力。结果表明,所得到的复合纳米粒子平均粒径100 nm左右,且分布均一,粒子呈纺锤状结构,在水溶液中具有良好的稳定性。FeOOH@PPy复合纳米粒子可以吸收808 nm的近红外光,并将其转化为足够的热量,使肿瘤细胞凋亡;在为期14天的4T1细胞的小鼠模型体内治疗实验中,FeOOH@PPy复合纳米粒子治疗组表现出优异的治疗肿瘤效果,组织分析表明FeOOH@PPy复合纳米粒子对小鼠正常组织无明显影响,具有作为光热治疗剂的潜力。     

介孔有机硅为载体的纳米递送系统制备及其体外化疗-光热联合治疗性能研究

有机/无机杂化的介孔有机硅纳米颗粒因其高的比表面积、丰富的介孔孔道、功能性的骨架以及高的药物装载量等特点而在生物医学领域受到广泛关注。本研究提出以二硫键桥接的有机/无机杂化介孔有机硅纳米颗粒为载体共装载化疗药物和光热剂,设计制备以DNA分子作为控释"开关"修饰介孔有机硅纳米颗粒的纳米递送系统(ICG/DOX-MONs@DNA₂₀)。该纳米递送系统结合了光热剂的光热效应以及DNA分子随温度升高而从颗粒表面脱附的特性,可实现近红外光照射激发药物在肿瘤细胞中的控制释放,同时获得药物化疗–光热联合治疗肿瘤的效果。实验结果表明,纳米递送系统在近红外光照下能迅速升温至43℃以上的热疗温度,而且在37℃条件下6h内仅缓慢释放药物12.3%,而当温度升至43℃时则快速释放药物52.4%;细胞实验显示该纳米递送系统能够被HeLa肿瘤细胞吞噬,在近红外光照下有明显的药物化疗-光热联合治疗效果。因此,ICG/DOX-MONs@DNA₂₀纳米递送系统在药物化疗-光热联合治疗肿瘤方面具有应用前景。     

光触发增强葡萄糖氧化酶催化活性的等离子体囊泡用于程序化光热-饥饿疗法

在肿瘤的饥饿治疗及协同治疗中,基于葡萄糖氧化酶(GOx)的纳米诊疗剂展现出具大的应用前景.自组装等离子体金囊泡(GV),由于具有独特的光学性能、巨大空腔和强局域表面等离子体共振等特性,可作为协同治疗的多功能纳米载体.本文中,我们开发了一种装载GOx的GV(GV-GOx)用于光触发释放GOx,同时增强GOx的催化活性,从而实现程序化光热-饥饿治疗.在近红外激光照射下,由于GV具有等离子体耦合效应, GV-GOx可以产生很强的局部高热,引起封装的GOx释放,同时高热可提高GOx催化活性,从而增强肿瘤的饥饿效应.此外,高光热效应可促进细胞对GV-GOx的摄取,并可通过活体光声/光热双模态成像对协同治疗进行有效监测.令人印象深刻的是,协同光热/饥饿疗法能完全消融4T1荷瘤小鼠的肿瘤,抗肿瘤效果明显优于单一疗法,且没有明显的系统毒性.本工作展示了一种光触发的纳米平台,可用于癌症协同治疗.     

超顺磁金纳米壳复合颗粒的粒径调控及其诊疗应用

利用原位还原-种子生长法制备了超顺磁金纳米壳复合颗粒(SGNs), 研究了其粒径调控的方法并对其体外/体内磁共振成像(MRI)和光热治疗(PT)性能进行了测试。结果表明, 通过改变Fe₃O₄的加入量可方便地调控SGNs的粒径, 并成功制备了粒径分别为100、150和200 nm的SGNs复合颗粒。这些不同粒径的纳米复合颗粒均具有规则的球形形貌、较窄的粒径分布和单分散性。经巯基-聚乙二醇(SH-PEG)修饰后, 不同粒径的复合颗粒(SGNs-PEG)均表现出较强的MRI成像和光热转换能力。其中, 粒径为150 nm的复合颗粒对808 nm激光具有最强的吸收能力和光热转换效率, 体外和体内可升高温度分别达37 ℃和25 ℃, 同时具有较优异的MRI成像造影能力。因此, 在MDA-MB-435荷瘤小鼠肿瘤部位注射该复合颗粒后, 可先对肿瘤部位进行很好的成像诊断, 再利用激光照射通过光热转换有效地杀灭肿瘤细胞, 这为实现肿瘤诊疗的一体化提供了可能。     

受体-供体-受体结构光疗试剂用于近红外二区荧光成像和光声成像引导的光动力和光热联合治疗（英文）

多模态成像引导的光动力和光热治疗在癌症治疗上具有明显的优势.同时具有近红外光(NIR)吸收、高活性氧(ROS)产率和高光热转换效率的物质是非常理想的光疗试剂.本文设计合成了一种具有“受体-供体-受体”(A-D-A)结构的分子IDCIC.随后通过在IDCIC表面包裹DSPE-PEG2000-NH₂得到了水溶性纳米颗粒IDCIC NPs. IDCIC NPs具有近红外吸收,峰值位于760 nm;同时还具有近红外二区荧光发射,峰值在1000 nm左右,荧光量子产率为1.2%,使得IDCIC NPs具有良好的光声成像和NIR-Ⅱ荧光成像能力.此外, IDCIC NPs在808 nm激光器照射下可以同时产生单线态氧(量子产率为9.1%)、羟基自由基(·OH)和热量(光热转换效率为78.9%).基于以上这些特性, IDCIC NPs可以用于多模态成像引导的光动力/光热联合癌症治疗.     

高光热效应碳球的快速制备及肿瘤细胞光热治疗

光热治疗是一种非侵入式的新型肿瘤治疗手段,可弥补传统治疗方式的不足。碳纳米材料作为一种高效的光热剂,在肿瘤光热治疗中表现出巨大的应用潜力。本研究采用超声辅助法使邻苯三酚与甲醛5 min快速聚合,经煅烧处理制备了单分散、粒径均一的碳球。该碳球兼具优良的细胞生物相容性和高光热转换效率。在808 nm近红外光照射下,碳球呈现良好的光热效应和光热稳定性,光热转换效率达到41.4%。细胞实验表明,碳球无明显细胞毒性,对肿瘤细胞具有显著的光热杀伤效果。制备的高光热效应碳球光热剂有望用于肿瘤光热治疗。     

程序化饥饿与光动力协同癌症治疗研究（英文）

协同治疗是指将多种治疗方法联合在一起使用,从而显著增强治疗效果.然而,如何设计出理想的组合以最大限度地发挥协同效应仍是肿瘤治疗的一大挑战.在此,我们构建了一种由葡萄糖氧化酶修饰的上转换纳米制剂,用于程序化的肿瘤饥饿-光动力协同治疗研究.葡萄糖氧化酶催化氧化肿瘤内的葡萄糖并产生过氧化氢,该过程消耗葡萄糖和氧气,使得肿瘤细胞缺乏营养物质处于"饥饿"状态,导致细胞死亡.并且在980 nm的近红外光激发下,上转换纳米颗粒激发产生紫外可见光,将双氧水裂解成毒性更强的羟基自由基,进一步杀死肿瘤细胞.体外和体内实验均证实这种饥饿-光动力协同治疗明显优于任何单一治疗.本研究为设计程序可控的饥饿-光动力协同治疗提供了理论支撑.     

Fabrication of multifunctional polydopamine-coated gold nanobones for PA/CT imaging and enhanced synergistic chemo-photothermal therapy

Multimodal imaging-guided chemo-photothermal therapy is an excellent cancer treatment,which can not only efficiently against tumor,but also can offer precise treatment window and real-time monitoring of the treatment efficiency.In our work,polydopamine(PDA)-coated gold nanobones(AuNBs@PDA nanocomplexes)were designed for this approach.The AuNBs@PDA nanocomplexes have strong absorbance in the near infrared(NIR)region and higher photothermal conversion efficiency(75.48%)than gold nanobones alone,which was facilitated for photoacoustic imaging and photothermal therapy.Besides,the loading efficiency of doxorubicin(DOX)by AuNBs@PDA nanocomplexes could be up to about 70%and DOX release from AuNBs@PDA/DOX nanocomplexes sensitively response to the lower pH environment and NIR laser irradiation,which makes them become the excellent nano-carrier for the delivery of chemotherapy drug.In vitro and in vivo studies showed significant cytotoxicity and antitumor efficacy by the AuNBs@PDA/DOX nanoplatform with negligible side effects.Meanwhile,the nanoplatform was also successfully employed for computed tomography(CT)imaging,attributing to the high atomic number and high X-ray attenuation coefficient of gold.Therefore,we believed that the proposed PDA-coated gold nanobones would be a novel multifunctional theranostic nanoagent to realize the PA/CT imaging-guided chemo-photothermal therapy of cancer.     

A Multilayered Mesoporous Gold Nanoarchitecture for Ultraeffective Near-Infrared Light-Controlled Chemo/Photothermal Therapy for Cancer Guided by SERS Imaging

Surface-enhanced Raman scattering (SERS) imaging has emerged as a promising tool for guided cancer diagnosis and synergistic therapies, such as combined chemotherapy and photothermal therapy (chemo-PTT). Yet, existing therapeutic agents often suffer from low SERS sensitivity, insufficient photothermal conversion, or/and limited drug loading capacity. Herein, a multifunctional theragnostic nanoplatform consisting of mesoporous silica-coated gold nanostar with a cyclic Arg-Gly-Asp (RGD)-coated gold nanocluster shell (named RGD–pAS@AuNC) is reported that exhibits multiple “hot spots” for pronouncedly enhanced SERS signals and improved near-infrared (NIR)-induced photothermal conversion efficiency (85.5%), with a large capacity for high doxorubicin (DOX) loading efficiency (34.1%, named RGD/DOX–pAS@AuNC) and effective NIR-triggered DOX release. This nanoplatform shows excellent performance in xenograft tumor model of HeLa cell targeting, negligible cytotoxicity, and good stability both in vitro and in vivo. By SERS imaging, the optimal temporal distribution of injected RGD/DOX–pAS@AuNCs at the tumor site is identified for NIR-triggered local chemo-PTT toward the tumor, achieving ultraeffective therapy in tumor cells and tumor-bearing mouse model with 5 min of NIR irradiation (0.5 W cm⁻²). This work offers a promising approach to employing SERS imaging for effective noninvasive tumor treatment by on-site triggered chemo-PTT.     

A Novel Top‐Down Synthesis of Ultrathin 2D Boron Nanosheets for Multimodal Imaging‐Guided Cancer Therapy

Single atom nonmetal 2D nanomaterials have shown considerable potential in cancer nanomedicines, owing to their intriguing properties and biocompatibility. Herein, ultrathin boron nanosheets (B NSs) are prepared through a novel top‐down approach by coupling thermal oxidation etching and liquid exfoliation technologies, with controlled nanoscale thickness. Based on the PEGylated B NSs, a new photonic drug delivery platform is developed, which exhibits multiple promising features for cancer therapy and imaging, including: i) efficient NIR‐light‐to‐heat conversion with a high photothermal conversion efficiency of 42.5%, ii) high drug‐loading capacity and triggered drug release by NIR light and moderate acidic pH, iii) strong accumulation at tumor sites, iv) multimodal imaging properties (photoacoustic, photothermal, and fluorescence imaging), and v) complete tumor ablation and excellent biocompatibility. As far as it is known, this is the first report on the top‐down fabrication of ultrathin 2D B NSs by the combined thermal oxidation etching and liquid exfoliation, as well as their application as a multimodal imaging‐guided drug delivery platform. The newly prepared B NSs are also expected to provide a robust and useful 2D nanoplatform for various biomedical applications.     

Development of CaP nanocomposites as photothermal actuators for doxorubicin delivery to enhance breast cancer treatment

Breast cancer is the most common one in women worldwide and doxorubicin(Dox)is one of the most commonly used and effective drugs for breast cancer treatment.Unfortunately,Dox-based chemotherapy faces irreversible cardiotoxicity and unsatisfactory therapy efficiency.It is desirable to devise Dox nanoformulations with less adverse effects and greater therapeutic efficacy for this cancer treatment.In this work,a multifunctional calcium phosphate nanoformulation(ICG-Dox/DNA@CaP)was developed by co-loading Dox/DNA complexes and indocyanine green(ICG)molecules for photothermal therapy(PTT)-enhanced chemotherapy.In this nanocomposite,using DNA as Dox carrier facilitated Dox loading into the CaP matrix,and significantly reduced Dox leakage as well as cytotoxicity in comparison with that of free Dox in physiological medium(pH 7.4).In specific,ICG-Dox/DNA@CaP only released Dox in a weakly acidic nuclease-containing environment,such as tumor microenvironment and endosome/lysosome.Moreover,Dox/DNA complexes exhibited synergistic interactions with ICG-based photothermal effect on tumor cell apoptosis in this ICG-Dox/DNA@CaP nanocomposite.This work has demonstrated a new strategy to combine FDA-approved therapeutics(Dox and ICG)in CaP-based nanomaterials for reduced cytotoxicity and enhanced therapeutic effect,and provided a new way to engineer CaP carriers as multifunctional delivery systems for clinical anti-cancer therapy.     

Intraoperative Raman‐Guided Chemo‐Photothermal Synergistic Therapy of Advanced Disseminated Ovarian Cancers

Abdominal miliary spread and metastasis is one of the most aggressive features in advanced ovarian cancer patients. The current standard treatment of advanced ovarian cancer is cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). However, most patients cannot receive optimal CRS outcomes due to the extreme difficulty of completely excising all microtumors during operation. Though HIPEC can improve prognosis, treatment is untargeted and may damage healthy organs and cause complications. New strategies for precise detection and complete elimination of disseminated microtumors without side effects are therefore highly desirable. Here, cisplatin‐loaded gap‐enhanced Raman tags (C‐GERTs) are designed specifically for the intraoperative detection and elimination of unresectable disseminated advanced ovarian tumors. With unique and strong Raman signals, good biocompatibility, decent plasmonic photothermal conversion, and good drug loading capacity, C‐GERTs enable detection and specific elimination of microtumors with a minimum diameter of 1 mm via chemo‐photothermal synergistic therapy, causing minimal side effects and significantly prolonging survival in mice. The results demonstrate that C‐GERTs‐based chemo‐photothermal synergistic therapy can effectively control the spread of disseminated tumors in mice and has potential as a safe and powerful method for treatment of advanced ovarian cancers, to improve survival and life quality of patients.     

Combined chemo/photothermal therapy based on mesoporous silica-Au core-shell nanoparticles for hepatocellular carcinoma treatment

Chemotherapy has been widely used for treatment to malignant cancer, such as hepatocellular carcinoma (HCC). Chemotherapeutic effect was not often efficient to achieve totally tumor ablation due to the poor cellular uptake and drug resistance. To address these problems, a novel nanoplatform was constructed based on nontoxic mesoporous silica nanoparticles (MSNs) for a combined chemo/photothermal therapy to enhance tumor cell accumulation and promote toxicity of chemotherapeutic drugs. Prepared MSNs were consisted of Au nanoshell for photothermal conversion and a first-line anti-HCC drug-sorafenib (SO) for chemotherapy. The SO-Au-MSNs could help SO accumulate more in hepatic cancer cells. Under near infrared irradiation, SO-Au-MSNs exerted a high cell inhibition rate which could be attributed to the enhanced toxicity of SO under hyperthermia and synergistic chemo/photothermal therapy. SO-Au-MSNs showed a good compatibility as well as efficient cell cytotoxicity. Overall, SO-Au-MSNs would be a promising candidate for further enhancing the antitumor effect on HCC.