Magnetically Engineered Semiconductor Quantum Dots as Multimodal Imaging Probes

Light‐emitting semiconductor quantum dots (QDs) combined with magnetic resonance imaging contrast agents within a single nanoparticle platform are considered to perform as multimodal imaging probes in biomedical research and related clinical applications. The principles of their rational design are outlined and contemporary synthetic strategies are reviewed (heterocrystalline growth; co‐encapsulation or assembly of preformed QDs and magnetic nanoparticles; conjugation of magnetic chelates onto QDs; and doping of QDs with transition metal ions), identifying the strengths and weaknesses of different approaches. Some of the opportunities and benefits that arise through in vivo imaging using these dual‐mode probes are highlighted where tumor location and delineation is demonstrated in both MRI and fluorescence modality. Work on the toxicological assessments of QD/magnetic nanoparticles is also reviewed, along with progress in reducing their toxicological side effects for eventual clinical use. The review concludes with an outlook for future biomedical imaging and the identification of key challenges in reaching clinical applications.     

Generation of white light from co-doped (Cu and Mn) ZnSe QDs

White light generation is achieved by single-step co-doping of copper and manganese into the robust ZnSe quantum dots (QDs) which were synthesised using a wet chemical route. Photoluminescence (PL) emission spectra revealed three peaks related to blue (ZnSe), green (copper related) and orange (manganese related). The PL spectra indicated no surface and/or trap state related emission. Photoluminescence excitation (PLE) measurements confirmed co-doping of copper and manganese in the same QD. PLE spectra recorded with emission wavelength fixed at copper and manganese showed a band edge at the same position, indicating the incorporation of both copper and manganese in the same QD. Time-resolved PL measurements suggest an atomic like nature of Mn and Cu in ZnSe QDs.     

Color-tunable Gd-Zn-Cu-ln-S/ZnS quantum dots for dual modality magnetic resonance and fluorescence imaging

Inorganic nanoparticles have been introduced into biological systems as useful probes for in vitro diagnosis and in vivo imaging, due to their relatively small size and exceptional physical and chemical properties. A new kind of color- tunable Gd-Zn-Cu-In-S/ZnS （GZCIS/ZnS） quantum dots （QDs） with stable crystal structure has been successfully synthesized and utilized for magnetic resonance （MR） and fluorescence dual modality imaging. This strategy allows successful fabrication of GZCIS/ZnS QDs by incorporating Gd into ZCIS/ZnS QDs to achieve great MR enhancement without compromising the fluorescence properties of the initial ZCIS/ZnS QDs. The as-prepared GZCIS/ZnS QDs show high T1 MR contrast as well as ＂color-tunable＂ photoluminescence （PL） in the range of 550-725 nm by adjusting the Zn/Cu feeding ratio with high PL quantum yield （QY）. The GZCIS/ZnS QDs were transferred into water via a bovine serum albumin （BSA） coating strategy. The resulting Cd-free GZCIS/ZnS QDs reveal negligible cytotoxicity on both HeLa and A549 cells. Both fluorescence and MR imaging studies were successfully performed in vitro and in vivo. The results demonstrated that GZCIS/ZnS QDs could be a dual-modal contrast agent to simultaneously produce strong MR contrast enhancement as well as fluorescence emission for in vivo imaging.     

CdSe/ZnSe量子点的制备及电化学发光性能

利用ZnSe半导体纳米材料晶体结构与CdSe相似、带隙更宽的特点,采用水热法合成了核-壳型CdSe/ZnSe量子点。结果表明：温度在70~160℃时,ZnSe壳逐渐包裹在CdSe核上,反应时间在0~4 h时,内壳在核上是均匀包裹的,当核壳摩尔比为1∶3时,CdSe/ZnSe QDs的电化学发光性能最强,其电化学发光强度是CdSe量子点的6倍,且发光信号稳定。     

Biofunctionalized,Phosphonate‐Grafted,Ultrasmall Iron Oxide Nanoparticles for Combined Targeted Cancer Therapy and Multimodal Imaging

A novel, inexpensive biofunctionalization approach is adopted to develop a multimodal and theranostic nanoagent, which combines cancer‐targeted magnetic resonance/optical imaging and pH‐sensitive drug release into one system. This multifunctional nanosystem, based on an ultrasmall superparamagnetic iron oxide (USPIO) nanocore, is modified with a hydrophilic, biocompatible, and biodegradable coating of N‐phosphonomethyl iminodiacetic acid (PMIDA). Using appropriate spacers, functional molecules, such as rhodamine B isothiocyanate, folic acid, and methotrexate, are coupled to the amine‐derivatized USPIO–PMIDA support with the aim of endowing simultaneous targeting, imaging, and intracellular drug‐delivering capability. For the first time, phosphonic acid chemistry is successfully exploited to develop a stealth, multifunctional nanoprobe that can selectively target, detect, and kill cancer cells overexpressing the folate receptor, while allowing real‐time monitoring of tumor response to drug treatment through dual‐modal fluorescence and magnetic resonance imaging.     

氮掺杂碳量子点的合成、表征及其在细胞成像中的应用

以葡萄糖和甘氨酸为混合碳源,在较低温度下经水热法一步合成了氮掺杂的荧光碳量子点(N-CQDs),然后对氮掺杂碳量子点的形貌、结构、组成、光学性质和细胞毒性进行了表征,最后将其应用于细胞成像。实验结果表明,对碳量子点进行氮掺杂能有效提高其荧光量子产率,其荧光增强是由于表面形成了大量强供电子基团,当葡萄糖和甘氨酸的质量比为2∶1时能获得最高为6.57%荧光量子产率。氮掺杂碳量子点还具有水溶性好、粒度均匀、优异的光致发光性质、低的细胞毒性、多波长成像等诸多优点,有望作为荧光探针应用于细胞成像等领域。     

A Versatile Theranostic Nanoemulsion for Architecture‐Dependent Multimodal Imaging and Dually Augmented Photodynamic Therapy

To design a clinically translatable nanomedicine for photodynamic theranostics, the ingredients should be carefully considered. A high content of nanocarriers may cause extra toxicity in metabolism, and multiple theranostic agents would complicate the preparation process. These issues would be of less concern if the nanocarrier itself has most of the theranostic functions. In this work, a poly(ethylene glycol)‐boron dipyrromethene amphiphile (PEG‐F₅₄‐BODIPY) with 54 fluorine‐19 (¹⁹F) is synthesized and employed to emulsify perfluorohexane (PFH) into a theranostic nanoemulsion (PFH@PEG‐F₅₄‐BODIPY). The as‐prepared PFH@PEG‐F₅₄‐BODIPY can perform architecture‐dependent fluorescence/photoacoustic/¹⁹F magnetic resonance multimodal imaging, providing more information about the in vivo structure evolution of nanomedicine. Importantly, this nanoemulsion significantly enhances the therapeutic effect of BODIPY through both the high oxygen dissolving capability and less self‐quenching of BODIPY molecules. More interestingly, PFH@PEG‐F₅₄‐BODIPY shows high level of tumor accumulation and long tumor retention time, allowing a repeated light irradiation after a single‐dose intravenous injection. The “all‐in‐one” photodynamic theranostic nanoemulsion has simple composition, remarkable theranostic efficacy, and novel treatment pattern, and thus presents an intriguing avenue to developing clinically translatable theranostic agents.     

Nebulized Gadolinium‐Based Nanoparticles: A Theranostic Approach for Lung Tumor Imaging and Radiosensitization

Lung cancer is the most common and most fatal cancer worldwide. Thus, improving early diagnosis and therapy is necessary. Previously, gadolinium‐based ultra‐small rigid platforms (USRPs) were developed to serve as multimodal imaging probes and as radiosensitizing agents. In addition, it was demonstrated that USRPs can be detected in the lungs using ultrashort echo‐time magnetic resonance imaging (UTE‐MRI) and fluorescence imaging after intrapulmonary administration in healthy animals. The goal of the present study is to evaluate their theranostic properties in mice with bioluminescent orthotopic lung cancer, after intrapulmonary nebulization or conventional intravenous administration. It is found that lung tumors can be detected non‐invasively using fluorescence tomography or UTE‐MRI after nebulization of USRPs, and this is confirmed by histological analysis of the lung sections. The deposition of USRPs around the tumor nodules is sufficient to generate a radiosensitizing effect when the mice are subjected to a single dose of 10 Gy conventional radiation one day after inhalation (mean survival time of 112 days versus 77 days for irradiated mice without USRPs treatment). No apparent systemic toxicity or induction of inflammation is observed. These results demonstrate the theranostic properties of USRPs for the multimodal detection of lung tumors and improved radiotherapy after nebulization.     

A Quantum Dot Photoswitch for DNA Detection,Gene Transfection,and Live‐Cell Imaging

Quantum dots (QDs) coated with an albumin‐derived copolymer shell exhibit significant photoresponsiveness to DNA loading and have great potential for investigating gene delivery processes. The QDs reported herein are positively charged, have attractive optical properties, and are noncytotoxic and notably stable in live cells. Their complex formation with plasmid DNA leads to proportionally decreased photoluminescence and efficient gene transfection is observed. Therefore, they are suitable for live‐cell bioimaging and mechanistic studies of nonviral gene delivery. Fluorescence correlation spectroscopy is applied for the first time to investigate individual QDs diffusing in large endosomes inside living cells, and serves as a valuable tool to study the physical properties of QDs inside live cells. The data obtained in this study strongly support the notable stability of these QDs, even in cell endosomes.     

Functional Carbon Quantum Dots for Ocular Imaging and Therapeutic Applications

Carbon quantum dots (CDs) are a class of emerging carbonaceous nanomaterials that have received considerable attention due to their excellent fluorescent properties, extremely small size, ability to penetrate cells and tissues, ease of synthesis, surface modification, low cytotoxicity, and superior water dispersion. In light of these properties, CDs are extensively investigated as candidates for bioimaging probes, efficient drug carriers, and disease diagnostics. Functionalized CDs represent a promising therapeutic candidate for ocular diseases. Here, this work reviews the potential use of functionalized CDs in the diagnosis and treatment of eye-related diseases, including the treatment of macular and anterior segment diseases, as well as targeting Aβ amyloids in the retina.