铁掺杂的聚2-硝基-1,4-苯二胺纳米球的制备及在光热/光动力/化学动力学肿瘤治疗中的应用

肿瘤微环境(TME)的复杂性,使得单一治疗方式很难实现完全治愈。 为此,构建了一种负载吲哚菁绿(ICG)的铁掺杂的聚2-硝基-1,4-苯二胺多功能纳米球Fe-PNPD-ICG(FPIs),用于光热(PTT)/光动力(PDT)/化学动力学(CDT)的联合治疗。 在808 nm激光器照射下,ICG作为光敏剂可以产生单线态氧,铁掺杂的聚2-硝基-1,4-苯二胺纳米球作为光热剂具有36.65%的光热转换效率。 FPIs一旦内化到肿瘤内,由Fe³⁺/Fe²⁺转化引发Fenton反应产生·OH实现化学动力学治疗,反应过程中可以清除TME中过表达的谷胱甘肽(GSH),从而降低肿瘤中的抗氧化能力。 同时,产生的氧气可以改善TME中乏氧情况,增强PDT的治疗效果。 因此,FPIs是PTT/PDT/CDT联合治疗的一种理想材料,在肿瘤治疗中具有潜在的应用前景。     

Folate-targeted co-delivery polymersomes for efficient photo-chemo-antiangiogenic therapy against breast cancer and in vivo evaluation via OCTA/NIRF dual-modal imaging

Intelligent nanoplatform that combines multimodal imaging and therapeutic effects holds great promise for precise and efficient cancer therapy. Herein, folate-targeted polymersomes with stimuli-responsiveness were fabricated and evaluated by near-infrared fluorescence (NIRF) and optical coherence tomography angiography (OCTA) dual-imaging for photo-chemo-antiangiogenic therapy against cancer. The folate-targeted polymersomes (FA-MIT-SIPS) not only integrated ammonium bicarbonate (ABC) and mitoxantrone (MIT) into their hydrophilic cavity but also encapsulated indocyanine green (ICG) and sorafenib (SOR) within their hydrophobic layer. NIRF imaging demonstrated that FA-MIT-SIPS effectively accumulated and retained in the tumors. Upon 808 nm laser irradiation, the ICG produced hyperthermia and reactive oxygen species (ROS) for efficient photothermal and photodynamic therapy. In addition, the decomposition of ABC in responsive to acidic tumor environment and ICG-induced hyperthermia accelerated drug release. The released MIT accumulated in nucleus to inhibit DNA synthesis, while the released SOR destructed tumor vascularization. Notably, OCTA imaging was applied to observe the tumor blood flow upon the combination therapy, demonstrating that FA-MIT-SIPS obviously decreased the vessels area density. Moreover, the synergistic photo-chemo-antiangiogenic therapy of FA-MIT-SIPS achieved excellent antitumor effect with 40% of the 4T1 tumor-bearing mice being completely cured without recurrence. The multifunctional polymersomes provide a promising dual-modal imaging-evaluated synergistic strategy for tumor therapy.     

Tumor Microenvironment Stimuli-Responsive Fluorescence Imaging and Synergistic Cancer Therapy by Carbon-Dot–Cu2+ Nanoassemblies

A method is developed to fabricate tumor microenvironment (TME) stimuli-responsive nanoplatform for fluorescence (FL) imaging and synergistic cancer therapy via assembling photosensitizer (chlorine e6, Ce6) modified carbon dots (CDs-Ce6) and Cu²⁺. The as-obtained nanoassemblies (named Cu/CC nanoparticles, NPs) exhibit quenched FL and photosensitization due to the aggregation of CDs-Ce6. Their FL imaging and photodynamic therapy (PDT) functions are recovered efficiently once they entering tumor sites by the stimulation of TME. Introducing of Cu²⁺ not only provides extra chemodynamic therapy (CDT) function through reaction with hydrogen peroxide (H₂O₂), but also depletes GSH in tumors by a redox reaction, thus amplifying the intracellular oxidative stress and enhancing the efficacy of reactive oxygen species (ROS) based therapy. Cu/CC NPs can act as a FL imaging guided trimodal synergistic cancer treatment agent by photothermal therapy (PTT), PDT, and thermally amplified CDT.     

Longitudinal analysis of novel Alzheimer's disease proteomic cerebrospinal fluid biomarkers during intravenous immunoglobulin therapy

Intravenous immunoglobulin (IVIg) therapy has shown promising results in treating Alzheimer's disease (AD). In this study, a Random Forest (RF) classification model was used to identify possible effects of IVIg on a group of eight subjects who underwent immunotherapy. Cerebrospinal fluid (CSF) samples from eight AD subjects who underwent IVIg therapy were collected before therapy, after 6 months of therapy, and after a 3-month drug washout period. Samples were analyzed using 2DE and further studied using a RF classification model to identify effects of IVIg on a panel of 23 putative diagnostic AD biomarkers previously identified. Six of the eight subjects showed improvements with respect to the 23 AD diagnostic biomarkers after 6 months of therapy compared to the samples taken at the outset of the trial. All subjects reverted back to baseline during drug washout. These results are also consistent with clinical observations. The observed improvements in subjects during 6 months of IVIg therapy and the reversion back to baseline during drug washout provides preliminary evidence regarding the potential use of IVIg as an AD immunotherapy.     

DNAzyme‐Loaded Metal–Organic Frameworks (MOFs) for Self‐Sufficient Gene Therapy

DNAzymes have been recognized as potent therapeutic agents for gene therapy, while their inefficient intracellular delivery and insufficient cofactor supply precludes their practical biological applications. Metal–organic frameworks (MOFs) have emerged as promising drug carriers without in‐depth consideration of their disassembled ingredients. Herein, we report a self‐sufficient MOF‐based chlorin e6‐modified DNAzyme (Ce6‐DNAzyme) therapeutic nanosystem for combined gene therapy and photodynamic therapy (PDT). The ZIF‐8 nanoparticles (NPs) could efficiently deliver the therapeutic DNAzyme without degradation into cancer cells. The pH‐responsive ZIF‐8 NPs disassemble with the concomitant release of the guest DNAzyme payloads and the host Zn²⁺ ions that serve, respectively, as messenger RNA‐targeting agent and required DNAzyme cofactors for activating gene therapy. The auxiliary photosensitizer Ce6 could produce reactive oxygen species (ROS) and provide a fluorescence signal for the imaging‐guided gene therapy/PDT.     

Biomimetic Cascade Polymer Nanoreactors for Starvation and Photodynamic Cancer Therapy

The selective disruption of nutritional supplements and the metabolic routes of cancer cells offer a promising opportunity for more efficient cancer therapeutics. Herein, a biomimetic cascade polymer nanoreactor (GOx/CAT-NC) was fabricated by encapsulating glucose oxidase (GOx) and catalase (CAT) in a porphyrin polymer nanocapsule for combined starvation and photodynamic anticancer therapy. Internalized by cancer cells, the GOx/CAT-NCs facilitate microenvironmental oxidation by catalyzing endogenous H₂O₂ to form O₂, thereby accelerating intracellular glucose catabolism and enhancing cytotoxic singlet oxygen (¹O₂) production with infrared irradiation. The GOx/CAT-NCs have demonstrated synergistic advantages in long-term starvation therapy and powerful photodynamic therapy (PDT) in cancer treatment, which inhibits tumor cells at more than twice the rate of starvation therapy alone. The biomimetic polymer nanoreactor will further contribute to the advancement of complementary modes of spatiotemporal control of cancer therapy.     

Cell Membrane-camouflaged Multi-functional Dendritic Large Pore Mesoporous Silica Nanoparticles for Combined Photothermal Therapy and Radiotherapy of Cancer

Combining photothermal therapy and radiotherapy(PTT-RT) with reducing tumor hypoxia acts as an important antitumor modality. However, it is a great challenge to realize photothermal therapy, radiotherapy and exogenous oxygen supply in one nanosystem. To realize a combination of the three functions, we fabricated a red blood cell membrane(RBCm)-camouflaged, red blood cell content(RBCc) and the copper sulfide(CuS) co-loaded dendritic large pore mesoporous silica nanoparticle(DLMSN/CuS/RBCc/ RBCm). The cell membrane coating endowed the nanoparticles with good stability in the physiological environment, and CuS allowed the nanoparticle exhibiting good photothermal and radiosensitization properties. RBCc loaded nanoparticle DLMSN/CuS/RBCc enhanced superior anti-tumor effect than DLMSN/CuS during combined PTT-RT therapy because the introduction of RBCc increased the exogenous oxygen supply. The in vitro study further demonstrated that the combination of photothermal therapy and radiotherapy induced superior antitumor efficacy than single therapy. Our work thus presents a unique multifunctional nanoscale platform favorable for combined PTT and RT.     

Light-stimulus Dual-drug Responsive Nanoparticles for Photoactivated Therapy Using Mesoporous Silica Nanospheres

Photoactivated therapy is an exciting new method of cancer treatment. A new light-stimulus dual-drug responsive nanoparticles based on mesoporous silica nanoparticles(MSN) were developed to control cellular anticancer drug release. The prepared Curcumin(Cur)-loaded nanoparticles MSN-Pt-PEG@Cur[PEG=poly(ethylene glycol)] could be activated by photostimulation to generate reactive oxygen species(ROS) from Cur and Pt(Ⅱ) from Pt(IV), respectively. Compared with free anti-cancer drugs' chemotherapy and single photoactivated therapy, the prepared MSN-Pt-PEG@Cur displayed increased cytotoxicity. Therefore, the strategy of light-stimulus dual-drug responsive nanoparticles is a promising approach to photoactivated therapy.     

Iridium photosensitizer constructed liposomes with hypoxia-activated prodrug to destrust hepatocellular carcinoma

Hypoxic tumor microenvironment is a major challenge for photodynamic therapy(PDT). To overcome this problem, PDT combined hypoxia-activated chemotherapy is a promising strategy for hypoxic cancer therapy. Herein, a multifunctional liposome(AQ4N-Ir1-sorafenib-liposome) is prepared by encapsulating a hypoxia-activated prodrug AQ4N, a photosensitizer iridium(III) complex and hepatocellular carcinoma(HCC) targeting drug sorafenib, for synergistic therapy of HCC. Ir1-mediated PDT upon irradiation ind...     

Multifunctional Nanoplatform Based on pH-responsive Micelle Coated with Discontinuous Gold Shell for Cancer Photothermo-chemotherapy and Photoacoustic Tomography

Photothermo-chemotherapy, as a new strategy for cancer treatment, incorporates the complementary advantages of photothermal therapy and chemotherapy. In this study, a pH-sensitive diblock copolymer poly(aspartic acid-butanediamine)-poly(2-(diisopropylamino)ethyl methacrylate) (PAsp(DAB)-PDPA) was synthesized and self-assembled into doxorubicin-loaded micelle, which was further used as a template to form a gold nanoshell. After further modification with poly(ethylene glycol), the resulting nanoplatform provided good biocompatibility and desirable photo-thermal conversion efficiency to facilitate photothermal therapy. Meanwhile the nanoparticle also exhibited pH sensitivity, which prevented drug loss while circulating in the blood but enabled rapid drug release after endocytosis. An improved effect was achieved with the combination of photothermal therapy and chemotherapy. In addition, systemic delivery of the nanoplatform could be monitored by photoacoustic tomography. Thereby, this multifunctional nanoplatform would be highly potential for the diagnosis and therapy of cancer.     

A supramolecular nanovehicle toward systematic,targeted cancer and tumor therapy

A supramolecular nanovehicle (denoted as SNV) was fabricated by encapsulating zinc phthalocyanine (ZnPc) and doxorubicin (DOX) into a copolymer (PVP-b-PAA-g-FA), so as to achieve systematic and synergistic chemotherapy-photodynamic therapy (PDT), targeted tumor imaging and therapy. The sophisticated copolymer designed in this work can load the PDT photosensitizer (ZnPc) and chemotherapy drug (DOX) simultaneously, which exhibits an excellent performance in chemotherapy-PDT targeted cancer and tumor therapy for both in vitro studies performed with HepG2 cells and in vivo tests with mice. This work provides a new drug formulation with a chemotherapy-PDT synergistic effect by virtue of the supramolecular material design, which possesses the advantages of an ultra-low drug dosage and highly-efficient in vivo targeted tumor imaging/therapy.     

Magnetic Mesoporous Silica Nanoparticles Cloaked by Red Blood Cell Membranes: Applications in Cancer Therapy

Targeted drug delivery is an emerging technological strategy that enables nanoparticle systems to be responsive for tumor therapy. Magnetic mesoporous silica nanoparticles (MMSNs) were cloaked with red blood cell membrane (RBC). This integrates long circulation, photosensitizer delivery, and magnetic targeting for cancer therapy. In vivo experiments demonstrate that RBC@MMSNs can avoid immune clearance and achieve magnetic field (MF)‐induced high accumulation in a tumor. When light irradiation is applied, singlet oxygen rapidly generates from hypocrellin B (HB)‐loaded RBC@MMSN and leads to the necrosis of tumor tissue. Such a RBC‐cloaked magnetic nanocarrier effectively integrates immunological adjuvant, photosensitizer delivery, MF‐assisted targeting photodynamic therapy, which provides an innovative strategy for cancer therapy.     

Selective photothermal therapy for breast cancer with targeting peptide modified gold nanorods

In this work, we prepared polyacrylic acid (PAA) coated gold nanorods (GNRs) and then the targeting peptide modified GNRs. The biocompatibility and stability of functionalized GNRs were investigated by monitoring the surface plasmon resonance (SPR) absorption intensity. The efficacy of targeted thermal therapy can be significantly enhanced via decoration with surface-bound peptide which was obtained through phage display technology. In addition, the photothermal therapy was monitored in real time with the multi-channel function of a confocal laser scanning microscope (CLSM) coupled with an 808 nm laser. This selective photothermal therapy of GNRs is a promising candidate for phototherapeutic applications.     

用于光动力治疗的四苯基卟啉衍生物研究进展

四苯基卟啉(TPP)衍生物的重要用途之一是用于光动力治疗(PDT)来破坏肿瘤组织.本文综述了近年来可用于光动力治疗的四苯基卟啉(TPP)衍生物的合成.通过对TPP衍生物进行官能团修饰,可以改善其物理、化学及生物性质,从而合成出可能用于PDT的卟啉衍生物.     

探讨妊娠糖尿病运用个体化营养膳食的影响

目的了解妊娠期糖尿病专业治疗中行个体化营养膳食疗法对其妊娠结局以及血糖控制水平产生的影响。方法选择130例因妊娠期糖尿病进入江西省萍乡市人民医院的患者,以膳食疗法的差异分组:62例Ⅰ组施以常规膳食疗法,68例Ⅱ组则施以个体化营养膳食疗法,再对两组病例血糖值及其妊娠结局专业统计、观察。结果施以两种膳食疗法后,62例Ⅰ组FPG值(5.60±0.90)mmol/L,68例Ⅱ组(4.47±0.49)mmol/L,(P<0.05);同时Ⅱ组2h PG值及其妊娠结局等都优于Ⅰ组,(P<0.05)。结论对于患有糖尿病的妊娠期患者,通过施以个体化营养膳食疗法,可实现对妊娠结局的充分改善,值得推荐应用。     

Conjugated Polymer Nanomaterials for Phototherapy of Cancer

Due to the excellent properties including high specificity,low side-effect and good biocompatibility,conjugated polymer nanomaterials have been served as efficient anticancer reagents in die past decades.According to the developed anticancer systems based on conjugated polymer nanomaterials,it could be summarized into three main cancer therapy strategies:photodynamic therapy(PDT),photothermal therapy(PTT)and combination therapy.In this mini review,we provide a brief introduction to three different cancer therapy modes,their mechanisms and potential biological applications.Furthermore,some perspectives on the further development of conjugated polymer nanomaterials are proposed in the territory of anticancer precision medicine.     

A Supramolecular Photosensitizer System Based on Nano-Cu/ZIF-8 Capped with Water-Soluble Pillar[6]arene and Methylene Blue Host–Guest Complexations

Photodynamic therapy (PDT) as a safe, non-invasive modality for cancer therapy, in which the low oxygen and high glutathione in the tumor microenvironment reduces therapeutic efficiency. In order to overcome these problems, we prepared a supramolecular photosensitive system of O₂-Cu/ZIF-8@ZIF-8@WP6–MB (OCZWM), which was loaded with oxygen to increase the oxygen concentration in the tumor microenvironment, and the Cu²⁺ in the system reacted with glutathione (GSH) to reduce the GSH concentration to generate Cu⁺. It is worth noting that the generated Cu⁺ can produce the Fenton reaction, thus realizing the combination therapy of PDT and chemodynamic therapy (CDT) to achieve the purpose of significantly improving the anti-cancer efficiency.     

Emerging Implications of Nonmammalian Cytosine Deaminases on Cancer Therapeutics

Nonmammalian cytosine deaminases (CDs) have been investigated for last 30?years in the context of cancer therapy. The therapeutic effect of CD is based on its ability to catalyze the conversion of nontoxic prodrug 5-fluorocytosine (5FC) into the anticancer drug 5-fluorouracil (5FU) by deamination of the number 4 carbon of 5FC. This deamination property of CD has been explored to develop innovative therapeutic approach for treatment of cancer. A general overview is needed for the identification of efficient cytosine deaminases for potential use in cancer therapy. In this review, we have discussed about nonmammalian CDs for a variety of prodrug gene/enzyme therapy applications with several recent examples. Finally, we have provided a prospective on the future aspects of CDs and their applications in cancer therapy.     

轻中度铅中毒儿童的干预治疗

为探讨轻中度铅中毒儿童的干预治疗的方法 ,将 96例血铅水平 10 0～ 4 0 0 μg/L的铅中毒儿童随机分成三组 :对照组为健康教育组 ;治疗A组为服钙组 ;治疗B组为混合组 :服食钙剂的同时 ,配合进行有关的健康教育。分别干预三个月后复查血铅水平。结果表明 ,三组儿童干预前后的血铅水平分别为 :对照组 (n =30 ) 2 0 6 0± 6 6 0 μg/L ,134 2± 4 2 9μg/L ,下降了 35% ;治疗A组(n =34) 2 0 8 5± 6 0 3μg/L ,12 4 0± 4 0 7μg/L ,下降了 4 1% ;治疗B组 (n =32 ) 2 2 5 9± 70 4 μg/L ,10 8 4± 33 8μg/L ,下降了 52 %。干预前各组间血铅水平没有差异 (P >0 0 5) ,而干预后对照组与治疗A组、对照组与治疗B组间比较 ,t分别为 0 970 (P >0 0 5)、2 6 36 (P <0 0 1) ,对照组与治疗B组之间有显著差异。提示健康教育及口服钙剂皆能明显降低轻中度铅中毒儿童的血铅水平 ,而两者同时配合进行 ,效果更加显著。     

Biocompatible Polymer-Modified Nanoplatform for Ferroptosis-Enhanced Combination Cancer Therapy

Ferroptosis is a novel type of iron-dependent non-apoptotic pathway that regulates cell death and shows unique mechanisms including causing lipid peroxide accumulation, sensitizing drug-resistant cancers, priming immunity by immunogenic cell death, and cooperatively acting with other anticancer modalities for eradicating aggressive malignancies and tumor relapse. Recently, there has been a great deal of effort to design and develop anticancer biocompatible polymeric nanoplatforms including polypeptide and PEGylated ones to achieve effective ferroptosis therapy (FT) and synergistic combination therapies including chemotherapy (CT), photodynamic therapy (PDT), sonodynamic therapy (SDT), photothermal therapy (PTT), gas therapy (GT) including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H₂S), and immunotherapy (IT). To be noted, the combo therapies such as FT-CT, FT-PTT, FT-GT, and FT-IT are attracting much efforts to fight against intractable and metastatic tumors as they can generate synergistic antitumor effects and immunogenic cell death (ICD) effects or modulate immunosuppressive tumor microenvironments to initiate strong antitumor immunity and memory effects. The polymeric Fenton nano-agents with good biosafety and high anticancer efficacy will provide a guarantee for their applications. In this review, various biocompatible polymer-modified nanoplatforms designed for FT and combo treatments are summarized for anticancer therapies and discussed for potential clinical transitions.