Multimodal Magnetic Nanoclusters for Gene Delivery,Directed Migration,and Tracking of Stem Cells

This study develops multimodal magnetic nanoclusters (M‐MNCs) for gene transfer, directed migration, and tracking of human mesenchymal stem cells (hMSCs). The M‐MNCs are designed with 5 nm iron oxide nanoparticles and a fluorescent dye (i.e., Rhodamine B) in the matrix of the Food and Drug Administration approved polymer poly(lactide‐co‐glycolide) using a nanoemulsion method. The synthesized M‐MNCs have a hydrodynamic diameter of ≈150 nm, are internalized by stem cells via endocytosis, and deliver genes with high efficiency. The cellular internalization and gene expression efficiency of the clustered nanoparticles are significantly higher than that of single nanoparticles. The M‐MNC‐labeled hMSCs migrate upon application of a magnetic force and can be visualized by both optical and magnetic resonance (MR) imaging. In animal models, the M‐MNC‐labeled hMSCs are also successfully tracked using optical and MR imaging. Thus, the M‐MNCs not only allow the efficient delivery of genes to stem cells but also the tracking of cells in animal models. Taken together, the results show that this new type of nanocomposite can be of great help in future stem cell research and in the development of cell‐based therapeutic agents.     

Ultra‐Small Iron Oxide Doped Polypyrrole Nanoparticles for In Vivo Multimodal Imaging Guided Photothermal Therapy

Recently, near‐infrared (NIR) absorbing conjugated polymeric nanoparticles have received significant attention in photothermal therapy of cancer. Herein, polypyrrole (PPy), a NIR‐absorbing conjugate polymer, is used to coat ultra‐small iron oxide nanoparticles (IONPs), obtaining multifunctional IONP@PPy nanocomposite which is further modified by the biocompatible polyethylene glycol (PEG) through a layer‐by‐layer method to acquire high stability in physiological solutions. Utilizing the optical and magnetic properties of the yielded IONP@PPy‐PEG nanoparticles, in vivo magnetic resonance (MR) and photoacoustic imaging of tumor‐bearing mice are conducted, revealing strong tumor uptake of those nanoparticles after intravenous injection. In vivo photothermal therapy is then designed and carried out, achieving excellent tumor ablation therapeutic effect in mice experiments. These results promise the use of multifunctional NIR‐absorbing organic‐inorganic hybrid nanomaterials, such as IONP@PPy‐PEG presented here, for potential applications in cancer theranostics.     

Multifunctional Upconversion Nanoparticles for Dual‐Modal Imaging‐Guided Stem Cell Therapy under Remote Magnetic Control

Stem cells have generated a great deal of excitement in cell‐based therapies. Here, a unique class of multifunctional nanoparticles (MFNPs) with both upconversion luminescence (UCL) and superparamagnetic properties is used for stem cell research. It is discovered that after being labeled with MFNPs, mouse mesenchymal stem cells (mMSCs) are able to maintain their viability and differentiation ability. In vivo UCL imaging of MFNP‐labeled mMSCs transplanted into animals is carried out, achieving ultrahigh tracking sensitivity with a detection limit as low as ≈10 cells in a mouse. Using both UCL optical and magnetic resonance (MR) imaging approaches, MFNP‐labeled mMSCs are tracked after being intraperitoneally injected into wound‐bearing mice under a magnetic field. The translocation of mMSCs from the injection site to the wound nearby the magnet is observed and, intriguingly, a remarkably improved tissue repair effect is observed as the result of magnetically induced accumulation of stem cells in the wound site. The results demonstrate the use MFNPs as novel multifunctional probes for labeling, in vivo tracking, and manipulation of stem cells, which is promising for imaging guided cell therapies and tissue engineering.     

Magnetic Targeting Enhanced Theranostic Strategy Based on Multimodal Imaging for Selective Ablation of Cancer

The booming development of nanomedicine offers great opportunities for cancer diagnostics and therapeutics. Herein, a magnetic targeting‐enhanced cancer theranostic strategy using a multifunctional magnetic‐plasmonic nano‐agent is developed, and a highly effective in vivo tumor photothermal therapy, which is carefully planed based on magnetic resonance (MR)/photoacoustic (PA) multimodal imaging, is realized. By applying an external magnetic field (MF) focused on the targeted tumor, a magnetic targeting mediated enhanced permeability and retention (MT‐EPR) effect is observed. While MR scanning provides tumor localization and reveals time‐dependent tumor homing of nanoparticles for therapeutic planning, photoacoustic imaging with higher spatial resolution allows noninvasive fine tumor margin delineation and vivid visualization of three dimensional distributions of theranostic nanoparticles inside the tumor. Utilizing the near‐infrared (NIR) plasmonic absorbance of those nanoparticles, selective photothermal tumor ablation, whose efficacy is predicted by real‐time infrared thermal imaging intra‐therapeutically, is carried out and then monitored by MR imaging for post‐treatment prognosis. Overall, this study illustrates the concept of imaging‐guided MF‐targeted photothermal therapy based on a multifunctional nano‐agent, aiming at optimizing therapeutic planning to achieve the most efficient cancer therapy.     

Multifunctional Magnetic Gold Nanocomposites: Human Epithelial Cancer Detection via Magnetic Resonance Imaging and Localized Synchronous Therapy

Novel multifunctional magnetic gold nanocomposites (MGNCs) were synthesized for synchronous cancer therapy and diagnosis via magnetic resonance imaging (MRI). The MGNCs consist of magnetic kernels (aggregates of ultra‐sensitive MnFe₂O₄ magnetic nanocrystals wrapped in polymer) as effective MR contrast agents and silica–gold nanocomposites as hyperthermal therapeutic agents. A therapeutic antibody, Erbitux (ERB), was conjugated for specific tumor cell targeting both to localize the near‐IR laser beam and to image their events through MRI. ERB‐conjugated MGNCs selectively recognize the target cancer cell lines. Fluorescence images and MRI analysis show that the MGNCs are effectively taken up by the cells. ERB‐conjugated MGNCs have an excellent synchronous therapeutic efficacy as a result of the therapeutic antibody and near‐IR laser‐induced surface plasmon resonance. Consequently, MGNCs clearly demonstrate selective imaging and treatment of human epithelial cancer simultaneously.     

Protamine Functionalized Single‐Walled Carbon Nanotubes for Stem Cell Labeling and In Vivo Raman/Magnetic Resonance/Photoacoustic Triple‐Modal Imaging

Stem cells have shown great potential in regenerative medicine and attracted tremendous interests in recent years. Sensitive and reliable methods for stem cell labeling and in vivo tracking are thus urgently needed. Here, a novel approach to label human mesenchymal stem cells (hMSCs) with single‐walled carbon nanotubes (SWNTs) for in vivo tracking by triple‐modal imaging is presented. It is shown that polyethylene glycol (PEG) functionalized SWNTs conjugated with protamine (SWNT‐PEG‐PRO) exhibit extremely efficient cell entry into hMSCs, without affecting their proliferation and differentiation. The strong inherent resonance Raman scattering of SWNTs is used for in vitro and in vivo Raman imaging of SWNT‐PEG‐PRO‐labeled hMSCs, enabling ultrasensitive in vivo detection of as few as 500 stem cells administrated into mice. On the other hand, the metallic catalyst nanoparticles attached on nanotubes can be utilized as the T2‐contrast agent in magnetic resonance (MR) imaging of SWNT‐labeled hMSCs. Moreover, in vivo photoacoustic imaging of hMSCs in mice is also demonstrated. The work reveals that SWNTs with appropriate surface functionalization have the potential to serve as multifunctional nanoprobes for stem cell labeling and multi‐modal in vivo tracking.     

Gold Nanoshell Nanomicelles for Potential Magnetic Resonance Imaging,Light‐Triggered Drug Release,and Photothermal Therapy

A novel multifunctional drug‐delivery platform is developed based on cholesteryl succinyl silane (CSS) nanomicelles loaded with doxorubicin, Fe₃O₄ magnetic nanoparticles, and gold nanoshells (CDF‐Au‐shell nanomicelles) to combine magnetic resonance (MR) imaging, magnetic‐targeted drug delivery, light‐triggered drug release, and photothermal therapy. The nanomicelles show improved drug‐encapsulation efficiency and loading level, and a good response to magnetic fields, even after the formation of the gold nanoshell. An enhancement for T₂‐weighted MR imaging is observed for the CDF‐Au‐shell nanomicelles. These nanomicelles display surface plasmon absorbance in the near‐infrared (NIR) region, thus exhibiting an NIR (808 nm)‐induced temperature elevation and an NIR light‐triggered and stepwise release behavior of doxorubicin due to the unique characteristics of the CSS nanomicelles. Photothermal cytotoxicity in vitro confirms that the CDF‐Au‐shell nanomicelles cause cell death through photothermal effects only under NIR laser irradiation. Cancer cells incubated with CDF‐Au‐shell nanomicelles show a significant decrease in cell viability only in the presence of both NIR irradiation and a magnetic field, which is attributed to the synergetic effects of the magnetic‐field‐guided drug delivery and the photothermal therapy. Therefore, such multicomponent nanomicelles can be developed as a smart and promising nanosystem that integrates multiple capabilities for effective cancer diagnosis and therapy.     

An Integrated Multifunctional Nanoplatform for Deep‐Tissue Dual‐Mode Imaging

The combination of biocompatible superparamagnetic and photoluminescent nanoparticles (NPs) is intensively studied as highly promising multifunctional (magnetic confinement and targeting, imaging, etc.) tools in biomedical applications. However, most of these hybrid NPs exhibit low signal contrast and shallow tissue penetration for optical imaging due to tissue‐induced optical extinction and autofluorescence, since in many cases, their photoluminescent components emit in the visible spectral range. Yet, the search for multifunctional NPs suitable for high photoluminescence signal‐to‐noise ratio, deep‐tissue imaging is still ongoing. Herein, a biocompatible core/shell/shell sandwich structured Fe₃O₄@SiO₂@NaYF₄:Nd³⁺ nanoplatform possessing excellent superparamagnetic and near‐infrared (excitation) to near‐infrared (emission), i.e., NIR‐to‐NIR photoluminescence properties is developed. They can be rapidly magnetically confined, allowing the NIR photoluminescence signal to be detected through a tissue as thick as 13 mm, accompanied by high T₂ relaxivity in magnetic resonance imaging. The fact that both the excitation and emission wavelengths of these NPs are in the optically transparent biological windows, along with excellent photostability, fast magnetic response, significant T₂‐contrast enhancement, and negligible cytotoxicity, makes them extremely promising for use in high‐resolution, deep‐tissue dual‐mode (optical and magnetic resonance) in vivo imaging and magnetic‐driven applications.     

Gadolinium‐Doped Persistent Nanophosphors as Versatile Tool for Multimodal In Vivo Imaging

Recent breakthroughs in the rational development of multifunctional nanocarriers have highlightened the advantage of combining the complementary forces of several imaging modalities into one single nanotool fully dedicated to the biomedical field and diagnosis applications. A novel multimodal optical‐magnetic resonance imaging nanoprobe is introduced. Designed on the basis of a spinel zinc gallate structure doped with trivalent chromium and gadolinium, this nanocrystal bears the ability to serve as both a highly sensitive persistent luminescence nanoprobe for optical imaging, and a negative contrast agent for highly resolved magnetic resonance imaging (MRI). Additional proof is given that surface coverage can be modified in order to obtain stealth nanoparticles highly suitable for real‐time in vivo application in mice, showing delayed reticulo‐endothelial uptake and longer circulation time after systemic injection.     

Hydroxyl‐Rich Polycation Brushed Multifunctional Rare‐Earth‐Gold Core–Shell Nanorods for Versatile Therapy Platforms

It is of great significance to develop a multifunctional imaging‐guided therapeutic platform with ideal resolution and sensitivity. Notably, rare‐earth (RE) nanoparticles are attractive candidates for multimodal imaging due to their unique optical and magnetic properties. In this work, a rational design of hierarchical nanohybrids employing RE‐Au hetero‐nanostructures is proposed. 1D RE nanorods are adopted as the core to facilitate cellular internalization with the coating of gold nanoshells for photothermal performances. Hydroxyl‐rich polycations with low cytotoxicity are grafted onto the surface of RE‐Au to produce RE‐Au‐PGEA (ethanolamine‐functionalized poly(glycidyl methacrylate)) nanohybrids with impressive gene transfection capability. Given the virtues of all the components, the feasibility of RE‐Au‐PGEA for multifunctional photoacoustic, computed tomography, magnetic resonance, upconversion luminescence imaging, and complementary photothermal therapy/gene therapy therapy is investigated in detail in vitro and in vivo. The visualization of the therapeutic processes with comprehensive information renders RE‐Au‐PGEA nanohybrid an intriguing platform to realize enhanced antitumor efficiency.     

Unprecedented “All‐in‐One” Lanthanide‐Doped Mesoporous Silica Frameworks for Fluorescence/MR Imaging and Combination of NIR Light Triggered Chemo‐Photodynamic Therapy of Tumors

Designing a single multifunctional nanoparticle that can simultaneously impart both diagnostic and therapeutic functions is considered to be a long‐lasting hurdle for biomedical researchers. Conventionally, a multifunctional nanoparticle can be constructed by integrating organic dyes/magnetic nanoparticles to impart diagnostic functions and anticancer drugs/photosensitizers to achieve therapeutic outcomes. These multicomponents systems usually suffer from severe photobleaching problems and cannot be activated by near‐infrared (NIR) light. Here, it is demonstrated that all‐in‐one lanthanide‐doped mesoporous silica frameworks (EuGdOx@MSF) loaded with an anticancer drug, doxorubicin (DOX) can facilitate simultaneous bimodal magnetic resonance (MR) imaging with approximately twofold higher T₁‐MR contrast as compared to the commercial Gd(III)‐DTPA complex and fluorescence imaging with excellent photostability. Upon a very low dose (130 mW cm^?2) of NIR light (980 nm) irradiation, the EuGdOx@MSF not only can sensitize formation of singlet oxygen (¹O₂) by itself but also can phototrigger the release of the DOX payload effectively to exert combined chemo‐photodynamic therapeutic (PDT) effects and destroy solid tumors in mice completely. It is also discovered for the first time that the EuGdOx@MSF‐mediated PDT effect can suppress the level of the key drug resistant protein, i.e., p‐glycoprotein (p‐gp) and help alleviate the drug resistant problem commonly associated with many cancers.     

Multifunctional Core/Shell Nanoparticles Self‐Assembled from pH‐Induced Thermosensitive Polymers for Targeted Intracellular Anticancer Drug Delivery

Core/shell nanoparticles that display a pH‐sensitive thermal response, self‐assembled from the amphiphilic tercopolymer, poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide‐co‐10‐undecenoic acid) (P(NIPAAm‐co‐DMAAm‐co‐UA)), have recently been reported. In this study, folic acid is conjugated to the hydrophilic segment of the polymer through the free amine group (for targeting cancer cells that overexpress folate receptors) and cholesterol is grafted to the hydrophobic segment of the polymer. This polymer also self‐assembles into core/shell nanoparticles that exhibit pH‐induced temperature sensitivity, but they possess a more stable hydrophobic core than the original polymer P(NIPAAm‐co‐DMAAm‐co‐UA) and a shell containing folate molecules. An anticancer drug, doxorubicin (DOX), is encapsulated into the nanoparticles. DOX release is also pH‐dependent. DOX molecules delivered by P(NIPAAm‐co‐DMAAm‐co‐UA) and folate‐conjugated P(NIPAAm‐co‐DMAAm‐co‐UA)‐g‐cholesterol nanoparticles enter the nucleus more rapidly than those transported by P(NIPAAm‐co‐DMAAm)‐b‐poly(lactide‐co‐glycolide) nanoparticles, which are not pH sensitive. More importantly, these nanoparticles can recognize folate‐receptor‐expressing cancer cells. Compared to the nanoparticles without folate, the DOX‐loaded nanoparticles with folate yield a greater cellular uptake because of the folate‐receptor‐mediated endocytosis process, and, thus, higher cytotoxicity results. These multifunctional polymer core/shell nanoparticles may make a promising carrier to target drugs to cancer cells and release the drug molecules to the cytoplasm inside the cells.     

“All‐in‐One” Nanoparticles for Trimodality Imaging‐Guided Intracellular Photo‐magnetic Hyperthermia Therapy under Intravenous Administration

Great efforts have been devoted so far to combine nano‐magnetic hyperthermia and nano‐photothermal therapy to achieve encouraging additive therapeutic performance in vitro and in vivo with limitation to direct intratumoral injection and no guidance of multimodality molecular imaging. In this study, a novel multifunctional theranostic nanoplatform (MNP@PES‐Cy7/2‐DG) consisting of magnetic nanoparticles (MNPs), poly(3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate) (PES), Cyanine7 (Cy7), and 2‐deoxyglucose (2‐DG)‐polyethylene glycol is developed. They are then applied to combined photo‐magnetic hyperthermia therapy under intravenous administration that is simultaneously guided by trimodality molecular imaging. Remarkably, nanoparticles are found aggregated mainly in the cytoplasm of tumor cells in vitro and in vivo, and exhibit stealth‐like behavior with a long second‐phase blood circulation half‐life of 20.38 ± 4.18 h. Under the guidance of photoacoustic/near‐infrared fluorescence/magnetic resonance trimodality imaging, tumors can be completely eliminated under intracellular photo‐magnetic hyperthermia therapy with additive therapeutic effect due to precise hyperthermia. This study may promote a further exploration of such a platform for clinical applications.     

Effect of Charge Density on Energy‐Transfer Properties of Cationic Conjugated Polymers

Cationic conjugated polymers (CCPs) with different charge densities are synthesized via Suzuki polymerization. The CCPs show similar optical properties in aqueous solutions but obvious difference in fluorescence resonance energy transfer (FRET) to Texas Red‐labeled single‐stranded DNA (ssDNA‐TR). Both CCP and TR fluorescence quenching are revealed to influence the energy‐transfer process. The difference in quantum yields of CCP/ssDNA complexes highlights the importance of polymer side‐chain structures and charge density. A CCP with a high charge density and ethylene oxide as the side chain provides the highest quantum yield for CCP/ssDNA complexes, which favors FRET. TR quenching within the CCP/ssDNA complexes is predominantly determined by the CCP charge density. In contrast to the other two polymers, the CCP with low charge density provides the most‐intense polymer‐sensitized TR emission, which is due to the collective response of more optically active polymer units around TR and the minimized TR self‐quenching within the CCP/ssDNA‐TR complexes. These studies provide a new guideline for improving the signal amplification of conjugated‐polymer‐based optical sensors.     

Self‐Assembly of Semiconducting Polymer Amphiphiles for In Vivo Photoacoustic Imaging

Despite the advantages of semiconducting polymer nanoparticles (SPNs) over other inorganic nanoparticles for photoacoustic (PA) imaging, their synthetic method is generally limited to nanoprecipitation, which is likely to cause the issue of nanoparticle dissociation. The synthesis of near‐infrared (NIR) absorbing semiconducting polymer amphiphiles (SPAs) that can spontaneously self‐assemble into homogeneous nanoparticles for in vivo PA imaging is reported. As compared with their counterpart nanoparticles (SPN1) prepared through nanoprecipitation, SPAs generally have higher fluorescence quantum yields but similar size and PA brightness, making them superior over SPN1. Optical and simulation studies reveal that the poly(ethylene glycol) (PEG) grafting density plays a critical role in determining the packing of SP segments inside the core of nanoparticles, consequently affecting the optical properties. The small size and structurally stable nanostructure, in conjunction with a dense PEG shell, allow SPAs to passively target tumors of living mice after systemic administration, permitting both PA and fluorescence imaging of the tumors at signals that are ≈1.5‐fold higher than that of liver. This study thus not only provides the first generation of amphiphilic optically active polymers for PA imaging, but also highlights the molecular guidelines for the development of organic NIR imaging nanomaterials.     

MRI‐Visible siRNA Nanomedicine Directing Neuronal Differentiation of Neural Stem Cells in Stroke

A major challenge in stroke treatment is the restoration of neural circuit in which neuron function plays a central role. Although transplantation of exogenous neural stem cells (NSCs) is admittedly a promising therapeutical means, the treatment outcome is greatly affected due to the poor NSCs differentiation into neurons caused by myelin associated inhibitory factors binding to Nogo‐66 receptor (NgR). Herein, a nanoscale polymersome is developed to codeliver superparamagnetic iron oxide nanoparticles and siRNA targeting NgR gene (siNgR) into NSCs. This multifunctional nanomedicine directs neuronal differentiation of NSCs through silencing the NgR gene and meanwhile allows a noninvasive monitoring of NSC migration with magnetic resonance imaging. An improved recovery of neural function is achieved in rat ischemic stroke model. The results demonstrate the great potential of the multifunctional siRNA nanomedicine in stroke treatment based on stem cell transplantation.     

Mussel Byssus‐Like Reversible Metal‐Chelated Supramolecular Complex Used for Dynamic Cellular Surface Engineering and Imaging

Inspired by the load‐bearing biostructures in nature, a multifunctional shell for encapsulating cell using the polyphenol–metal complexes is fabricated. The artificial shell is formed by cross‐linking of tannic acid and iron ion on cell surface. It can protect cells from unfriendly environments, including UV light irradiation and reactive oxygen damage. With the hybrid property of polyphenol and metal liands, the shell provides a versatile platform for cell surface engineering. The magnetic nanoparticles, DNA molecules, as well as the magnetic resonance imaging agents are easily incorporated into the shell. More interestingly, unlike the traditional passive coatings, here the shell can be controllably disassembled under external stimuli. The dynamic coating is used as a reversible element to regulate cell division and surface modification. The cell viability and protein expression experiments further confirm that the shell formation and degradation processes are biocompatible. This multifunctional coating strategy is applicable to multiple living cell types, including yeast cells, Escherichia coli bacteria, and mammalian cells. Therefore, this platform would be useful for living cell based fundamental research and biological applications.     

Fast and Accurate Imaging of Lymph Node Metastasis with Multifunctional Near‐Infrared Polymer Dots

Metastasis to regional lymph nodes is a significant prognostic indicator for cancer progression. There is a great demand for rapid and accurate diagnosis of metastasis to the lymph nodes. In this work, folate receptor‐targeted trimodal polymer dots are designed for near‐infrared (NIR)/photoacoustic (PA)/magnetic resonance (MR) imaging of lymph node metastasis. Confocal microscopic analyses and flow cytometry show that pulmonary mucosa epithelial cell carcinoma NCI‐H292 with expression of the folate receptor is positive for folate‐functional polymer dots. In vivo and ex vivo NIR imaging results verify that prepared polymer dots show rapid and high uptake in the metastatic lymph nodes, can effectively distinguish metastatic and normal lymph nodes for 1 h postinjection, and have great potential in real‐time imaging‐guided surgery. Furthermore, ten metastatic lymph nodes from the tumor‐bearing mice are detected by NIR imaging via intratumoral injection of polymer dots. Moreover, in vivo PA and MR imaging confirm the enhanced PA and MR signals of polymer dots in the metastatic lymph nodes as well as enlarged lymph nodes in tumor‐bearing mice. The results of this study provide a unique approach using trimodal polymer dots for the rapid and precise diagnosis of lymph node metastasis in vivo.     

Well‐Defined Protein‐Based Supramolecular Nanoparticles with Excellent MRI Abilities for Multifunctional Delivery Systems

Protein‐based nanoparticles are widely used for effective biomedical applications. The objective of this work is to design series of magnetic resonance imaging (MRI)‐visible cationic supramolecular nanoparticles (PGEA@BSA‐Ad/Gd³⁺) based on bovine serum albumin (BSA) and β‐cyclodextrin‐cored star ethanolamine‐functionalized poly(glycidyl methacrylate) (CD‐PGEA) in the presence of Gd³⁺ ions for multifunctional delivery systems. CD‐PGEA is prepared via atom transfer radical polymerization and ring‐opening reaction. It is found that in the absence of Gd³⁺ ions, CD‐PGEA does not well interact with adamantine‐modified BSA (BSA‐Ad). The well‐defined PGEA@BSA‐Ad/Gd³⁺ supramolecular nanoparticles could be produced through the synergistic actions of the host–guest and electrostatic self‐assemblies by mixing aqueous solutions of CD‐PGEA, BSA‐Ad, and Gd³⁺. In comparison with CD‐PGEA assembly units, such kinds of uniform PGEA@BSA‐Ad/Gd³⁺ supramolecular nanoparticles exhibit better pDNA condensation ability, lower cytotoxicity, higher gene transfection, and easier cellular uptake. In addition, PGEA@BSA‐Ad/Gd³⁺ also produces outstanding MRI abilities, much better than Magnevist (Gd‐diethylenetriaminepentacetate acid). The present design of protein–polymer supramolecular nanoparticles with MRI contrast agents would provide a new way for multifunctional gene/drug delivery systems.     

Biomimetic Natural Killer Membrane Camouflaged Polymeric Nanoparticle for Targeted Bioimaging

In the present study, a biomimetic nanoconstruct (BNc) with a multimodal imaging system is engineered using tumor homing natural killer cell membrane (NKM), near‐infrared (NIR) fluorescent dye, and gadolinium (Gd) conjugate‐based magnetic resonance imaging contrast agent onto the surface of a polymeric nanoparticle. The engineered BNc is 110 ± 20 nm in size and showed successful retention of NKM proteins. The magnetic properties of the BNc are found to be tunable from 2.1 ± 0.17 to 5.3 ± 0.5 mm ^?1 s^?1 under 14.1 T, by adjusting the concentration of Gd‐lipid conjugate onto the surface of the BNc. Confocal imaging and cell sorting analysis reveal a distinguishable cellular interaction of the BNc with MCF‐7 cells in comparison to that of bare polymeric nanoparticles suggesting the tumor homing properties of NKM camouflage system. The in vitro cellular interaction results are further confirmed by in vivo NIR fluorescent tumor imaging and ex vivo MR imaging, respectively. Pharmacokinetics and biodistribution analysis of the BNc show longer circulation half‐life (≈9.5 h) and higher tumor accumulation (10% of injected dose) in MCF‐7 induced tumor‐bearing immunodeficient NU/NU nude mice. Owing to the proven immunosurveillance potential of NK‐cell in the field of immunotherapy, the BNc engineered herein would hold promises in the design consideration of nanomedicine engineering.