尾静脉注射方法考察Stearic-PEI/SPIO 纳米基因载体的基因转染性能及磁共振可视化效果研究

实验应用硬脂酸-聚乙烯亚胺包裹超顺磁氧化铁(Superparamagnetic Iron Oxide,SPIO)装载目的基因构建可视化 纳米复合物,进行 BABL/c 雌性小鼠体内磁共振成像实验、组织学检测,探讨其是否能够有效地介导体内基因表达以及 产生磁共振成像(Magnetic Resonance Imaging,MRI)效果。MRI 实验结果显示,对小鼠尾静脉注射复合物 0.5 小时后进 行磁共振扫描,与注射生理盐水的对照组相比实验组 T2 加权信号明显降低,信号强度仅为对照组的 35%;48 小时后, 实验组 T2 加权信号强度略有回升,但与对照组信号强度相比仍存在显著差异。组织学结果显示可视化基因纳米复合物 能够穿过血管内皮细胞进入肝脏组织,并释放 DNA 在细胞内成功表达,但基因表达效果较差。综合 MRI 成像及组织检 查实验结果可知,该纳米颗粒具有优良的 MRI 成像性能,但通过尾静脉注射方法基因转染效率较低。     

Nanoheterojunction Engineering Enables NIR-II-Triggered Photonic Hyperthermia and Pyroelectric Catalysis for Tumor-Synergistic Therapy

Photodynamic therapy (PDT) as a non-invasive strategy shows high promise in cancer treatment. However, owing to the hypoxic tumor microenvironment and light irradiation-mediated rapid electron–hole pair recombination, the therapeutic efficacy of PDT is dramatically discounted by limited reactive oxygen species (ROS) generation. Herein, a multifunctional theranostic nanoheterojunction is rationally developed, in which 2D niobium carbide (Nb₂C) MXene is in situ grown with barium titanate (BTO) to generate a robust photo-pyroelectric catalyst, termed as BTO@Nb₂C nanosheets, for enhanced ROS production, originating from the effective electron–hole pair separation induced by the pyroelectric effect. Under the second near-infrared (NIR-II) laser irradiation, Nb₂C MXene core-mediated photonic hyperthermia regulates temperature variation around BTO shells facilitating the electron–hole spatial separation, which reacts with the surrounding O₂ and H₂O molecules to yield toxic ROS, achieving a synergetic effect by means of combinaterial photothermal therapy with pyrocatalytic therapy. Correspondingly, the engineered BTO@Nb₂C composite nanosheets feature benign biocompatibility and high antitumor efficiency with the tumor-inhibition rate of 94.9% in vivo, which can be applied as an imaging-guided real-time non-invasive synergetic dual-mode therapeutic nanomedicine for efficient tumor nanotherapy.     

A Phase Engineering Strategy of Perovskite-Type ZnSnO3:Nd for Boosting the Sonodynamic Therapy Performance

The sensitization performance of sonosensitizers plays a key role in the sonodynamic therapy (SDT) effect. Herein, ZnSnO₃:Nd nanoparticles with R3c phase/amorphous heterogeneous structure are developed by phase engineering strategy and applied as an ideal sonosensitizer. In the crystalline perovskite-type ZnSnO₃:Nd, the substitution of the Zn²⁺ with Nd³⁺ causes the O 2p non-bonded state to move toward the Fermi level, which optimizes the band structure for ultrasound sensitization by reducing bandgap. Meanwhile, the unequal charge substitution can also form electron traps and oxygen vacancies to shorten the electron migration distance, which accelerates the electron–hole separation and inhibits carrier recombination, thus improving the acoustic sensitivity. Moreover, the dangling bonds exposed on the surface of amorphous ZnSnO₃:Nd provide more active sites, and the localized states of the amorphous phase may also promote carrier separation, resulting in synergistic SDT effect. In particular, the Zn²⁺ released from ZnSnO₃:Nd in the acidic tumor microenvironment (TME) reduces the adenosine triphosphate production by inhibiting the electron transport chain , which promotes the tumor cell apoptosis through destroying the redox balance of TME. Combining the inherent second near infrared and computed tomography imaging capabilities, this ZnSnO₃:Nd nanoplatform shows a promising perspective in clinic SDT field.     

A NIR-II AIEgen-Based Supramolecular Nanodot for Peroxynitrite-Potentiated Mild-Temperature Photothermal Therapy of Hepatocellular Carcinoma

Compared to conventional photothermal therapy (PTT) which requires hyperthermia higher than 50 °C, mild-temperature PTT is a more promising antitumor strategy with much lower phototoxicity to neighboring normal tissues. However, the therapeutic efficacy of mild-temperature PTT is always restricted by the thermoresistance of cancer cells. To address this issue, a supramolecular drug nanocarrier is fabricated to co-deliver nitric oxide (NO) and photothermal agent DCTBT with NIR-II aggregation-induced emission (AIE) characteristic for mild-temperature PTT. NO can be effectively released from the nanocarriers in intracellular reductive environment and DCTBT is capable of simultaneously producing reactive oxygen species (ROS) and hyperthermia upon 808 nm laser irradiation. The generated ROS can further react with NO to produce peroxynitrite (ONOOˉ) bearing strong oxidization and nitration capability. ONOOˉ can inhibit the expression of heat shock proteins (HSP) to reduce the thermoresistance of cancer cells, which is necessary to achieve excellent therapeutic efficacy of DCTBT-based PTT at mild temperature (<50 °C). The antitumor performance of ONOOˉ-potentiated mild-temperature PTT is validated on subcutaneous and orthotopic hepatocellular carcinoma (HCC) models. This research puts forward an innovative strategy to overcome thermoresistance for mild-temperature PTT, which provides new inspirations to explore ONOOˉ-sensitized tumor therapy strategies.     

Can twice weekly hemodialysis expand patient access under resource constraints?

The convention of prescribing hemodialysis on a thrice weekly schedule began empirically when it seemed that this frequency was convenient and likely to treat symptoms for a majority of patients. Later, when urea was identified as the main target and marker of clearance, studies supported the prevailing notion that thrice weekly dialysis provided appropriate clearance of urea. Today, national guidelines on hemodialysis from most countries recommend patients receive at least thrice weekly therapy. However, resource constraints in low‐ and middle‐income countries (LMIC) have resulted in a substantial proportion of patients using less frequent hemodialysis in these settings. Observational studies of patients on twice weekly dialysis show that twice weekly therapy has noninferior survival rates compared with thrice weekly therapy. In fact, models of urea clearance also show that twice weekly therapy can meet urea clearance “targets” if patients have significant residual function or if they follow a protein‐restricted diet, as may be common in LMIC. Greater reliance on twice weekly therapy, at least at the start of hemodialysis, therefore has potential to reduce health care costs and increase access to renal replacement therapy in low‐resource settings; however, randomized control trials are needed to better understand long‐term outcomes of twice versus thrice weekly therapy.     

Poly(N‐phenylglycine)‐Based Nanoparticles as Highly Effective and Targeted Near‐Infrared Photothermal Therapy/Photodynamic Therapeutic Agents for Malignant Melanoma

Malignant melanoma is a highly aggressive tumor resistant to chemotherapy. Therefore, the development of new highly effective therapeutic agents for the treatment of malignant melanoma is highly desirable. In this study, a new class of polymeric photothermal agents based on poly(N‐phenylglycine) (PNPG) suitable for use in near‐infrared (NIR) phototherapy of malignant melanoma is designed and developed. PNPG is obtained via polymerization of N‐phenylglycine (NPG). Carboxylate functionality of NPG allows building multifunctional systems using covalent bonding. This approach avoids complicated issues typically associated with preparation of polymeric photothermal agents. Moreover, PNPG skeleton exhibits pH‐responsive NIR absorption and an ability to generate reactive oxygen species, which makes its derivatives attractive photothermal therapy (PTT)/photodynamic therapy (PDT) dual‐modal agents with pH‐responsive features. PNPG is modified using hyaluronic acid (HA) and polyethylene glycol diamine (PEG‐diamine) acting as the coupling agent. The resultant HA‐modified PNPG (PNPG‐PEG‐HA) shows negligible cytotoxicity and effectively targets CD44‐overexpressing cancer cells. Furthermore, the results of in vitro and in vivo experiments reveal that PNPG‐PEG‐HA selectively kills B16 cells and suppresses malignant melanoma tumor growth upon exposure to NIR light (808 nm), indicating that PNPG‐PEG‐HA can serve as a very promising nanoplatform for targeted dual‐modality PTT/PDT of melanoma.     

A Metal–Polyphenol Network Coated Nanotheranostic System for Metastatic Tumor Treatments

As a characteristic trait of most tumor types, metastasis is the major cause of the death of patients. In this study, a photothermal agent based on gold nanorod is coated with metal (Gd³⁺)‐organic (polyphenol) network to realize combination therapy for metastatic tumors. This nanotheranostic system significantly enhances antitumor therapeutic effects in vitro and in vivo with the combination of photothermal therapy (PTT) and chemotherapy, also can remarkably prevent the invasion and metastasis due to the presence of polyphenol. After the treatment, an 81% decrease in primary tumor volumes and a 58% decrease in lung metastasis are observed. In addition, the good performance in magnetic resonance imaging, computerized tomography, and photothermal imaging of the nanotheranostic system can realize image‐guided therapy. The multifunctional nanotheranostic system will find a great potential in diagnosis and treatment integration in tumor treatments, and broaden the applications of PTT treatment.     

Catalase-imprinted Fe<Subscript>3</Subscript>O<Subscript>4</Subscript>/Fe@fibrous SiO<Subscript>2</Subscript>/polydopamine nanoparticles: An integrated nanoplatform of magnetic targeting,magnetic resonance imaging,and dual-mode cancer therapy

Recent advances in the research on the molecular mechanism of cell death and methods for preparation of nanomaterials make the integration of various therapeutic approaches,targeting,and imaging modes into a single nanoscale complex a new trend for the development of future nanotherapeutics.Hence,a novel ellipsoidal composite nanoplatform composed of a magnetic Fe3O4/Fe nanorod core (～120 nm) enwrapped by a catalase (CAT)-imprinted fibrous SiO2/ polydopamine (F-SiO2/PDA) shell with thickness 70 nm was prepared in this work.In vitro experiments showed that the Fe3O4/Fe@F-SiO2/PDA nanoparticles can selectively inhibit the bioactivity of CAT in tumor cells by the molecular imprinting technique.As a result,the H2O2 level in tumor cells was elevated dramatically.At the same time,the Fe3O4/Fe core released Fe ions to catalyze the conversion of H2O2 to ·OH in tumor cells.Eventually,the concentration of ·OH in tumor cells rapidly rose to a lethal level thus triggering apoptosis.Combined with the remarkable near-infrared light (NIR) photothermal effect of the CATimprinted PDA layer,the Fe3O4/Fe@F-SiO2/PDA nanoparticles can effectively kill MCF-7,HeLa,and 293T tumor cells but are not toxic to nontumor cells.Furthermore,these nanoparticles show good capacity for magnetic targeting and suitability for magnetic resonance imaging (MRI).Therefore,the integrated multifunctional nanoplatform opens up new possibilities for high-efficiency visual targeted nonchemo therapy for cancer.