A Molecular Brush Approach to Enhance Quantum Yield and Suppress Nonspecific Interactions of Conjugated Polyelectrolyte for Targeted Far‐Red/Near‐Infrared Fluorescence Cell Imaging

A red‐fluorescent conjugated polyelectrolyte (CPE, P2 ) is grafted with dense poly(ethylene glycol) (PEG) chains via click chemistry and subsequently modified with folic acid to form a molecular brush based cellular probe ( P4 ). P4 self‐assembles into a core–shell nanostructure in aqueous medium with an average size of 130 nm measured by laser light scattering. As compared to P2 , P4 possesses not only a substantially higher quantum yield (11%), but also reduced nonspecific interactions with biomolecules in aqueous medium due to the shielding effect of PEG. In conjunction with its high photostability and low cytotoxicity, utilization of P4 as a far‐red/near‐infrared cellular probe allows for effective visualization and discrimination of MCF‐7 cancer cells from NIH‐3T3 normal cells in a high contrast, selective, and nonviral manner. This study thus demonstrates a flexible molecular brush approach to overcome the intrinsic drawbacks of CPEs for advanced bioimaging applications.     

Cypate‐Conjugated Porous Upconversion Nanocomposites for Programmed Delivery of Heat Shock Protein 70 Small Interfering RNA for Gene Silencing and Photothermal Ablation

Synergistic therapy is an accepted method of enhancing the efficacy of cancer therapies. In this study, cypate‐conjugated porous NaLuF₄ doped with Yb³⁺, Er³⁺, and Gd³⁺ is synthesized and its potential for upconversion luminescence/magnetic resonance dual‐modality molecular imaging for guiding oncotherapy is tested. Loading cypate‐conjugated upconversion nanoparticles (UCNP‐cy) with small interfering RNA gene against heat shock protein 70 (UCNP‐cy‐siRNA) enhances the cell damage. UCNP‐cy‐siRNA exhibits remarkable antitumor efficacy in vivo as a result of the synergistic effects of gene silencing and photothermal therapy, with low drug dose and minimal side effects. This result thus provides an explicit strategy for developing next‐generation multifunctional nanoplatforms for multimodal imaging‐guided synergistic oncotherapy.     

Silica‐Coated Manganese Oxide Nanoparticles as a Platform for Targeted Magnetic Resonance and Fluorescence Imaging of Cancer Cells

Monodisperse silica‐coated manganese oxide nanoparticles (NPs) with a diameter of ～35 nm are synthesized and are aminated through silanization. The amine‐functionalized core–shell NPs enable the covalent conjugation of a fluorescent dye, Rhodamine B isothiocyanate (RBITC), and folate (FA) onto their surface. The formed Mn₃O₄@SiO₂(RBITC)–FA core–shell nanocomposites are water‐dispersible, stable, and biocompatible when the Mn concentration is below 50 µg mL^?1 as confirmed by a cytotoxicity assay. Relaxivity measurements show that the core–shell NPs have a T₁ relaxivity (r₁) of 0.50 mM ^?1 s^?1 on the 0.5 T scanner and 0.47 mM ^?1 s^?1 on the 3.0 T scanner, suggesting the possibility of using the particles as a T₁ contrast agent. Combined flow cytometry, confocal microscopy, and magnetic resonance imaging studies show that the Mn₃O₄@SiO₂(RBITC)–FA nanocomposites can specifically target cancer cells overexpressing FA receptors (FARs). Findings from this study suggest that the silica‐coated Mn₃O₄ core–shell NPs could be used as a platform for bimodal imaging (both magnetic resonance and fluorescence) in various biological systems.     

Poly(cyclodextrin)‐Polydrug Nanocomplexes as Synthetic Oncolytic Virus for Locoregional Melanoma Chemoimmunotherapy

Despite the approval of oncolytic virus (OV) therapy for advanced melanoma, its intrinsic limitations that include the risk of persistent viral infection and cost‐intensive manufacturing motivate the development of analogous approaches that are free from the disadvantages of virus‐based therapies. Herein, reported is a nanoassembly comprised of multivalent host–guest interactions between polymerized paclitaxel (pPTX) and nitric oxide‐incorporated polymerized β‐cyclodextrin (pCD‐pSNO) that through its bioactive components and when used locoregionally recapitulates the therapeutic effects of OV. The resultant pPTX/pCD‐pSNO exhibits significantly enhanced cytotoxicity, immunogenic cell death, dendritic cell (DC) activation, and T cell expansion in vitro compared to free agents alone or in combination. In vivo, intratumoral administration of pPTX/pCD‐pSNO results in activation and expansion of DCs systemically, but with a corresponding expansion of myeloid‐derived suppressor cells and suppression of CD8⁺ T cell expansion. When combined with antibody targeting cytotoxic T lymphocyte antigen‐4 that blunts this molecule's signaling effects on T cells, intratumoral pPTX/pCD‐pSNO treatment elicits potent anticancer effects that significantly prolong animal survival. This formulation thus leverages the chemo‐ and immunotherapeutic synergies of PTX and nitric oxide and suggests the potential for virus‐free nanoformulations to mimic the therapeutic action and benefits of OVs.     

Amplification of Cerenkov Luminescence Using Semiconducting Polymers for Cancer Theranostics

The therapeutic efficacy of photodynamic therapy is limited by the ability of light to penetrate tissues. Due to this limitation, Cerenkov luminescence (CL) from radionuclides has recently been proposed as an alternative light source in a strategy referred to as Cerenkov radiation-induced therapy (CRIT). Semiconducting polymer nanoparticles (SPNs) have ideal optical properties, such as large absorption cross-sections and broad absorbance, which can be utilized to harness the relatively weak CL produced by radionuclides. SPNs can be doped with photosensitizers and have ≈100% energy transfer efficiency by multiple energy transfer mechanisms. Herein, an optimized photosensitizer-doped SPN is investigated as a nanosystem to harness and amplify CL for cancer theranostics. It is found that semiconducting polymers significantly amplify CL energy transfer efficiency. Bimodal positron emission tomography (PET) and optical imaging studies show high tumor uptake and retention of the optimized SPNs when administered intravenously or intratumorally. Lastly, it is found that photosensitizer-doped SPNs have excellent potential as a cancer theranostics nanosystem in an in vivo tumor therapy study. This study shows that SPNs are ideally suited to harness and amplify CL for cancer theranostics, which may provide a significant advancement for CRIT that are unabated by tissue penetration limits.     

人体组织拉曼光谱研究进展

介绍了拉曼光谱测量技术在人体皮肤、血液、乳腺、胃、肺等组织疾病诊断中的研究概况,同时介绍了拉曼测量新技术的发展概况,展望了它的发展前景.     

TiO2/MXene-Assisted LDI-MS for Urine Metabolic Profiling in Urinary Disease

Cancer remains an intractable medical problem. Rapid diagnosis and identification of cancer are critical to differentiate it from nonmalignant diseases. High-throughput biofluid metabolic analysis has potential for cancer diagnosis. Nevertheless, the present metabolite analysis method does not meet the demand for high-throughput screening of diseases. Herein, a high-throughput, cost-effective, and noninvasive urine metabolic profiling method based on TiO₂/MXene-assisted laser desorption/ionization mass spectrometry (LDI-MS) is presented for the efficient screening of bladder cancer (BC) and nonmalignant urinary disease. Combined with machine learning, TiO₂/MXene-assisted LDI-MS enables high diagnostic accuracy (96.8%) for the classification of patient groups (including 47 BC and 46 ureteral calculus (UC) patients) from healthy controls (113 cases). In addition, BC patients can also be identified from noncancerous UC individuals with an accuracy of 88.3% in the independent test cohort. Furthermore, metabolite variations between BC and UC individuals are investigated based on relative quantification, and related pathways are also discussed. These results suggest that this method, based on urine metabolic patterns, provides a potential tool for rapidly distinguishing urinary diseases and it may pave the way for precision medicine.     

小鼠在体皮下乳腺癌的太赫兹波成像检测研究

乳腺癌是女性常见癌症之一,乳腺癌区域的精准检测对乳腺癌的治疗有至关重要的作用。本文采用频率为2.52THz的连续太赫兹波反射式成像系统,对小鼠在体皮下乳腺癌模型进行了太赫兹波成像检测。研究结果表明,太赫兹波成像可以清晰识别出乳腺癌区域,且与肉眼可见肿瘤区域一致。在体乳腺癌区域的太赫兹波相对反射率高于正常组织,两者相对反射率差值高达15%。进一步,对距离皮肤表面不同深度的离体乳腺癌组织进行切片和苏木精-伊红(H&E)染色,作为金标准对照。结果发现乳腺癌区域的面积随着距离皮肤表面深度的增加而增大。通过将太赫兹波成像与H&E染色结果对比可知,在距离皮肤表面约460μm处,太赫兹波图像和H&E染色图中的肿瘤区域面积相等。由此可知,太赫兹波对在体皮下乳腺癌的探测深度大约在460μm左右,太赫兹波有望实现深部肿瘤的检测。     

Smart Injectable Hydrogels for Cancer Immunotherapy

Hydrogels, a class of materials with a 3D network structure, are widely used in various fields especially in biomedicine. Injectable hydrogels could facilitate the encapsulation and controlled release of small molecular drugs, macromolecular therapeutics, and even cells. With the rapid development of cancer immunotherapy, such injectable hydrogels have attracted wide attention for local immunomodulation to boost systemic anticancer immune responses, realizing more effective immunotherapy at lower doses. The latest progresses in the development of various smart injectable hydrogels for cancer immunotherapy are summarized here. Although applied locally, such injectable hydrogels can activate systemic antitumor immune responses, safely and effectively inhibiting the tumor metastasis and recurrence. Moreover, it is discussed how injectable hydrogel‐based cancer immunotherapy would contribute to the development of next generation of cancer treatment together with their potential for clinical translation.