RGD‐Conjugated Nanoscale Coordination Polymers for Targeted T1‐ and T2‐weighted Magnetic Resonance Imaging of Tumors in Vivo

Development of multifunctional nanoscale coordination polymers (NCPs) allowing for T₁‐ and T₂‐weighted targeted magnetic resonance (MR) imaging of tumors could significantly improve the diagnosis accuracy. In this study, nanoscale coordination polymers (NCPs) with a diameter of ≈80 nm are obtained with 1,1′‐dicarboxyl ferrocene (Fc) as building blocks and magnetic gadolinium(III) ions as metallic nodes using a nanoprecipitation method, then further aminated through silanization. The amine‐functionalized Fc‐Gd@SiO₂ NCPs enable the covalent conjugation of a fluorescent rhodamine dye (RBITC) and an arginine‐glycine‐aspartic acid (RGD) peptide as a targeting ligand onto their surface. The formed water‐dispersible Fc‐Gd@SiO₂(RBITC)–RGD NCPs exhibit a low cytotoxicity, as confirmed by MTT assay. They have a longitudinal relaxivity (r₁) of 5.1 mM^?1 s^?1 and transversal relaxivity (r₂) of 21.7 mM^?1 s^?1, suggesting their possible use as both T₁‐positive and T₂‐negative contrast agents. In vivo MR imaging experiments show that the signal of tumor over‐expressing high affinity α_vβ₃ integrin from T₁‐weighted MR imaging is positively enhanced 47±5%, and negatively decreased 33±5% from T₂‐weighted MR imaging after intravenous injection of Fc‐Gd@SiO₂(RBITC)–RGD NCPs.     

Activated Surface Charge‐Reversal Manganese Oxide Nanocubes with High Surface‐to‐Volume Ratio for Accurate Magnetic Resonance Tumor Imaging

Investigating the surface structure, including crystal surface and surface‐coating ligands, of nanoparticulate T₁ contrast agent may help to understand the T₁ relaxation enhancement in vitro and in vivo. This study presents a novel strategy to develop high‐performance T₁ magnetic resonance imaging (MRI) contrast agents through optimizing the nanocrystal surface and the nanobio interface. Based on the optimized crystal surface, the novel manganese oxide nanocubes (MOCs) show significantly higher surface‐to‐volume ratio and an approximately threefold higher r₁ value compared to traditional manganese oxide nanospheres. Concurrently, transferring MOCs into aqueous media by dopamine derivatization can avoid the oxidation of Mn(II) ions and provide abundant magnetic core. This optimized surface endows MOCs with a high chemical exchange efficiency during T₁ relaxation. Of particular significance, a rationally designed pH‐induced charge‐switchable surfaces can be negatively charged and corona‐free in blood and positively charged surface in tumor sites. This unique feature improves the circulation behavior of this intelligent T₁ contrast agent in blood and increases cancer cell uptake to achieve accurate detection of solid tumor, holding great potential in aiding early and precise tumor diagnosis. This study provides a novel tool for sophisticated design of high‐performance T₁ MRI contrast agents in bioimaging applications.     

Nitroxide Radicals@US‐Tubes: New Spin Labels for Biomedical Applications

The encapsulation of nitroxide radicals within ultrashort (ca. 50 nm) single‐walled carbon nanotubes (US‐tubes) is achieved. Tempo‐ and Iodo‐Tempo@US‐tubes are characterized by thermogravimetric analysis (TGA), X‐ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Electron paramagnetic resonance (EPR) spectra display characteristic signals due to the detection of the spin probes within the US‐tubes. Longitudinal proton relaxivities (r₁) of both nitroxide@US‐tubes samples are 7 to 13 times greater than the free nitroxide radicals in solution, giving relaxivities comparable to the clinical contrast agent (CA) Magnevist. In addition, transverse proton relaxivities (r₂) show unprecedented proton relaxation enhancement in comparison to any other reported nitroxide radical‐based system or the clinically approved T₂ CA, Resovist, under the same conditions. T₂‐weighted magnetic resonance imaging (MRI) phantom images show that the encapsulation of nitroxide radicals within the US‐tubes produces good contrast enhancement due to their high r₂ relaxivities. The nitroxide radicals@US‐tube agents are a new promising class of spin probes for MRI and electronic paramagnetic resonance imaging (EPRI) labeling, tracking, and diagnosis.     

Ultrasmall Water‐Soluble and Biocompatible Magnetic Iron Oxide Nanoparticles as Positive and Negative Dual Contrast Agents

Monodispersed water‐soluble and biocompatible ultrasmall magnetic iron oxide nanoparticles (UMIONs, D = 3.3 ± 0.5 nm) generated from a high‐temperature coprecipitation route are successfully used as efficient positive and negative dual contrast agents of magnetic resonance imaging (MRI). Their longitudinal relaxivity at 4.7 T (r₁ = 8.3 mM^?1 s^?1) is larger than that of clinically used T₁‐positive agent Gd‐DTPA (r₁ = 4.8 mM^?1 s^?1), and three times that of commercial contrast agent SHU‐555C (r₁ = 2.9 mM^?1 s^?1). The transversal relaxivity (r₂ = 35.1 mM^?1 s^?1) is six times that of Gd‐DTPA (r₂ = 5.3 mM^?1 s^?1), half of SHU‐555C (r₂ = 69 mM^?1 s^?1). The in vivo results show that the liver signal from T₁‐weighted MRI is positively enhanced 26%, and then negatively decreased 20% after injection of the iron oxide nanoparticles, which is stronger than those obtained from Gd‐DTPA (<10%) using the same dosage. The kidney signal is positively enhanced up to 35%, similar to that obtained from Gd‐DTPA. Under T₂‐weighted conditions, the liver signal is negatively enhanced ?70%, which is significantly higher than that from Gd‐DTPA (?6%). These results demonstrate the great potential of the UMIONs in dual contrast agents, especially as an alternative to Gd‐based positive contrast agents, which have risks of inducing side effects in patients.     

Enhanced Relaxometric Properties of MRI “Positive” Contrast Agents Confined in Three‐Dimensional Cubic Mesoporous Silica Nanoparticles

Mesoporous silica nanoparticles (MSNs) are of growing interest for the development of novel probes enabling efficient tracking of cells in vivo using magnetic resonance imaging (MRI). The incorporation of Gd³⁺ paramagnetic ions into highly porous MSNs is a powerful strategy to synthesize “positive” MRI contrast agents for more quantitative T₁‐weighted MR imaging. Within this context, different strategies have been reported to integrate Gd chelates to 2D pore network MSNs. As an alternative, we report on the modulation of the pore network topology through the preparation of a 3D pore network hybrid GdSi_xO_y MSN system. In this study, 2D GdSi_xO_y‐MSNs with similar porosity and particle size were also prepared and the relaxometric performances of both materials, directly compared. Both syntheses lead to water‐dispersible MSNs suspensions (particle size < 200 nm), which were stable for at least 48h. 3D GdSi_xO_y‐MSNs provided a significant increase in ¹H longitudinal relaxivity (18.5 s^?1mM^?1; 4.6 times higher than Gd‐DTPA) and low r₂/r₁ ratios (1.56) compatible with the requirements of “positive” contrast agents for MRI. These results demonstrate the superiority of a 3D pore network to host paramagnetic atoms for MRI signal enhancement using T₁‐weighted imaging. Such an approach minimizes the total amount of paramagnetic element per particle.     

Single Ho3+‐Doped Upconversion Nanoparticles for High‐Performance T2‐Weighted Brain Tumor Diagnosis and MR/UCL/CT Multimodal Imaging

Multimodal bio‐imaging has attracted great attention for early and accurate diagnosis of tumors, which, however, suffers from the intractable issues such as complicated multi‐step syntheses for composite nanostructures and interferences among different modalities like fluorescence quenching by MRI contrast agents (e.g., magnetic iron oxide NPs). Herein, the first example of T₂‐weighted MR imaging of Ho³⁺‐doped upconversion nanoparticles (UCNPs) is presented, which, very attractively, could also be simultaneously used for upconversion luminesence (UCL) and CT imaging, thus enabling high performance multi‐modal MRI/UCL/CT imagings in single UCNPs. The new finding of T₂‐MRI contrast enhancement by integrated sensitizer (Yb³⁺) and activator (Ho³⁺) in UCNPs favors accurate MR diagnosis of brain tumor and provides a new strategy for acquiring T₂‐MRI/optical imaging without fluorescence quenching. Unlike other multi‐phased composite nanostructures for multimodality imaging, this Ho³⁺‐doped UCNPs are featured with simplicity of synthesis and highly efficient multimodal MRI/UCL/CT imaging without fluorescence quenching, thus simplify nanostructure and probe preparation and enable win–win multimodality imaging.     

Molecularly Engineered Biodegradable Polymer Networks with a Wide Range of Stiffness for Bone and Peripheral Nerve Regeneration

To satisfy different mechanical requirements in hard and soft tissue replacements, a series of biodegradable and crosslinkable copolymers of poly(propylene fumarate)‐co‐polycaprolactone (PPF‐co‐PCL) are synthesized and employed to fabricate 2D disks and 3D scaffolds via photocrosslinking. Thermal properties such as the glass transition temperature (T_g) and melting temperature (T_m) of the PPF‐co‐PCL networks can be controlled efficiently by varying the PCL composition (φ_PCL). As a result, their mechanical properties vary significantly from hard and stiff materials to soft and flexible ones with increasing φ_PCL, making them attractive candidate materials for bone and peripheral nerve regeneration, respectively. Several PPF‐co‐PCL formulations are selected to perform in vitro cell studies using mouse pre‐osteoblastic MC3T3‐E1, rat Schwann cell precursor line (SPL201), and pheochromocytoma (PC12) cells, and in vivo animal testing in the rat femur bone defect model and in the rat sciatic nerve transection model. The formation of new bone in the porous bone scaffolds with a low φ_PCL and guided axon growth through the nerve conduits with a higher φ_PCL suggest that crosslinked PPF‐co‐PCLs have appropriate compatibility and functionality. Furthermore, the role of surface stiffness in modulating cellular behavior and functions is verified on the crosslinked PPF‐co‐PCL surfaces without any pretreatments.     

Positive and Negative Lattice Shielding Effects Co‐existing in Gd (III) Ion Doped Bifunctional Upconversion Nanoprobes

Gadolinium (Gd) doped upconversion nanoparticles (UCNPs) have been well documented as T₁‐MR and fluorescent imaging agents. However, the performance of Gd³⁺ ions located differently in the crystal lattice still remains debatable. Here, a well‐designed model was built based on a seed‐mediated growth technique to systematically probe the longitudinal relaxivity of Gd³⁺ ions within the crystal lattice and at the surface of UCNPs. We found, for the first time, a nearly 100% loss of relaxivity of Gd³⁺ ions buried deeply within crystal lattices (> 4 nm), which we named a “negative lattice shielding effect” (n‐LSE) as compared to the “positive lattice shielding effect” (p‐LSE) for the enhanced upconversion fluorescent intensity. As‐observed n‐LSE was further found to be shell thickness dependent. By suppressing the n‐LSE as far as possible, we optimized the UCNPs' structure design and achieved the highest r₁ value (6.18 mM^?1s^?1 per Gd³⁺ ion) among previously reported counterparts. The potential bimodal imaging application both in vitro and in vivo of as‐designed nano‐probes was also demonstrated. This study clears the debate over the role of bulk and surface Gd³⁺ ions in MRI contrast imaging and paves the way for modulation of other Gd‐doped nanostructures for highly efficient T₁‐MR and upconversion fluorescent bimodal imaging.     

Surface Engineered Polymersomes for Enhanced Modulation of Dendritic Cells During Cardiovascular Immunotherapy

The principle cause of cardiovascular disease (CVD) is atherosclerosis, a chronic inflammatory condition characterized by immunologically complex fatty lesions within the intima of arterial vessel walls. Dendritic cells (DCs) are key regulators of atherosclerotic inflammation, with mature DCs generating pro‐inflammatory signals within vascular lesions and tolerogenic DCs eliciting atheroprotective cytokine profiles and regulatory T‐cell (Treg) activation. Here, the surface chemistry and morphology of synthetic nanocarriers composed of poly(ethylene glycol)‐b‐poly(propylene sulfide) copolymers to enhance the targeted modulation of DCs by transporting the anti‐inflammatory agent 1,25‐dihydroxyvitamin D3‐(aVD) and ApoB‐100‐derived antigenic peptide P210 are engineered. Polymersomes decorated with an optimized surface display and density for a lipid construct of the P‐D2 peptide, which binds CD11c on the DC surface, significantly enhance the cytosolic delivery and resulting immunomodulatory capacity of aVD in vitro. Weekly low‐dose intravenous administration of DC‐targeted, aVD‐loaded polymersomes significantly inhibit atherosclerotic lesion development in high‐fat‐diet‐fed ApoE^?/? mice. The results validate the key role of DC immunomodulation during aVD‐dependent inhibition of atherosclerosis and demonstrate the therapeutic enhancement and dosage lowering capability of cell‐targeted nanotherapy in the treatment of CVD.     

Inhibition of Ion Migration for Reliable Operation of Organolead Halide Perovskite‐Based Metal/Semiconductor/Metal Broadband Photodetectors

Organolead halide perovskites (OHPs) have attracted extensive attention as light harvesting materials for solar cells recently, because of their high charge carrier mobility, high photoconversion efficiencies, low cost, and simple methodology. Despite these advantages, the OHPs exhibit sweep‐dependent hysteresis behavior in current–voltage characteristics films, deteriorating the reliability of devices based on the OHPs. This study demonstrates reliable high on/off ratio (I_on/I_off = 10⁴) CH₃NH₃PbI₃ broadband photodetectors with buffer layer‐free simple metal/semiconductor/metal lateral structure. At high external bias, poor on/off ratios and spikes in dark current and photocurrent are observed due to the migration of charged defect ions. The ion migration can be effectively inhibited at low external bias, and thus the devices show high I_on/I_off ratios and spike‐free dark current and photocurrent. In addition, prevention of the prepoling in the CH₃NH₃PbI₃ films by operating at the low external bias results in pronouncedly enhanced signal‐to‐noise ratios even under low intensity incident light. These results strongly propose that inhibiting the migration of charged defect ions in CH₃NH₃PbI₃ films is a key in developing reliable high performance CH₃NH₃PbI₃‐based devices.     

Design and Synthesis of Multifunctional Drug Carriers Based on Luminescent Rattle‐Type Mesoporous Silica Microspheres with a Thermosensitive Hydrogel as a Controlled Switch

A novel approach for the fabrication of multifunctional microspheres integrating several advantages of mesoporous, luminescence, and temperature responses into one single entity is reported. First, the hollow mesoporous silica capsules are fabricated via a sacrificial template route. Then, Gd₂O₃:Eu³⁺ luminescent nanoparticles are incorporated into the internal cavities to form rattle‐type mesoporous silica nanocapsules by an incipient‐wetness impregnation method. Finally, the rattle‐type capsules serve as a nanoreactor for successfully filling temperature‐responsive hydrogel via photoinduced polymerization to form the multifunctional composite microspheres. The organic–inorganic hybrid microspheres show a red emission under UV irradiation due to the luminescent Gd₂O₃:Eu³⁺ core. The in vitro cytotoxicity tests show that the samples have good biocompatibility, which indicates that the nanocomposite could be a promising candidate for drug delivery. In addition, flow cytometry and confocal laser scanning microscopy (CLSM) confirm that the sample can be effectively taken up by SKOV3 cells. For in vitro magnetic resonance imaging (MRI), the sample shows the promising spin‐lattice relaxation time (T₁) weighted effect and could potentially apply as a T₁‐positive contrast agent. This composite drug delivery system (DDS) provides a positive temperature controlled “on‐off”drug release pattern and the drug, indomethacin (IMC), is released fast at 45 °C (on phase) and completely shut off at 20 °C (off phase). Meanwhile Gd₂O₃:Eu³⁺ plays an important role as the luminescent tag for tracking the drug loading and release process by the reversible luminescence quenching and recovery phenomenon. These results indicate that the obtained multifunctional composite has the potential to be used as a smart DDS for biomedical applications.     

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.     

Nanoshells with Targeted Simultaneous Enhancement of Magnetic and Optical Imaging and Photothermal Therapeutic Response

Integrating multiple functionalities into individual nanoscale complexes is of tremendous importance in biomedicine, expanding the capabilities of nanoscale structures to perform multiple parallel tasks. Here, the ability to enhance two different imaging technologies simultaneously—fluorescence optical imaging and magnetic resonance imaging—with antibody targeting and photothermal therapeutic actuation is combined all within the same nanoshell‐based complex. The nanocomplexes are constructed by coating a gold nanoshell with a silica epilayer doped with Fe₃O₄ and the fluorophore ICG, which results in a high T₂ relaxivity (390 mM ^?1 s^?1) and 45× fluorescence enhancement of ICG. Bioconjugate nanocomplexes target HER2+ cells and induce photothermal cell death upon near‐IR illumination.     

Multifunctional Mesoporous Nanoellipsoids for Biological Bimodal Imaging and Magnetically Targeted Delivery of Anticancer Drugs

A general polyelectrolyte‐mediated self‐assembly technique is adopted to prepare multifunctional mesoporous nanostructures as an effective biological bimodal imaging probe and magnetically targeted anticancer drug (doxorubicin) delivery systems (DDSs). A positively charged polyelectrolyte (PAH) and negatively charged fluorescent quantum dots (QDs) are successfully assembled onto the surface of ellipsoidal Fe₃O₄@SiO₂@mSiO₂ composite nanostructures to combine the merits of tunable fluorescent/magnetic properties, mesoporous nanostructures for drug loading, and the uniform ellipsoidal morphology for enhanced uptake by cancer cells. The resultant nanoellipsoids are homogeneously coated with four layers of PAH/QDs, with an additional PAH layer to make the ellipsoidal surface positively charged. This acts to enhance cellular uptake, which is driven by electrostatic interactions between the positive nanoparticle surface and the negative cell surface. The high biocompatibility of the achieved multifunctional nanoellipsoids is demonstrated by a cell‐cytotoxicity assay, hemolyticity against human red blood cells, and coagulation evaluation of fresh human blood plasma after exposure to the nanoparticles. Moreover, confocal microscopy and bio‐TEM observations show that the cell uptake of nanocarriers is dose‐dependent, and the nanoparticles accumulate mostly in the cytoplasm. The excellent capability of the nanocarriers as contrast agents for MRI is demonstrated by the relatively high r₂ value (143 mM^?1s^?1) and preliminary in vivo characterization. More importantly, the doxorubicin‐loaded DDSs show higher cytotoxicity than the free doxorubicin drug as contributed by the intracellular release pathway of doxorubicin from the DDSs, indicating the potential application of the obtained multifunctional mesoporous nanoellipsoids as highly effective bimodal imaging probes and DDSs for cancer diagnosis and chemotherapy, simultaneously.     

Remarkable NIR Enhancement of Multifunctional Nanoprobes for In Vivo Trimodal Bioimaging and Upconversion Optical/T2‐Weighted MRI‐Guided Small Tumor Diagnosis

Effective nanoprobes and contrast agents are urgently sought for early‐stage cancer diagnosis. Upconversion nanoparticles (UCNPs) are considerable alternatives for bioimaging, cancer diagnosis, and therapy. Yb³⁺/Tm³⁺ co‐doping brings both emission and excitation wavelengths into the near‐infrared (NIR) region, which is known as “optical transmission window” and ideally suitable for bioimaging. Here, NIR emission intensity is remarkably enhanced by 113 times with the increase of Yb³⁺ concentration from 20% to 98% in polyethylene glycol (PEG) modified NaYF₄:Yb³⁺/Tm³⁺ UCNPs. PEG‐UCNPs‐5 (98% Yb³⁺) can act as excellent nanoprobes and contrast agents for trimodal upconversion (UC) optical/CT/T₂‐weighted magnetic resonance imaging (MRI). In addition, the enhanced detection of lung in vivo long‐lasting tracking, as well as possible clearance mechanism and excretion routes of PEG‐UCNPs‐5 have been demonstrated. More significantly, a small tumor down to 4 mm is detected in vivo via intravenous injection of these nanoprobes under both UC optical and T₂‐weighted MRI modalities. PEG‐UCNPs‐5 can emerge as bioprobes for multi‐modal bioimaging, disease diagnosis, and therapy, especially the early‐stage tumor diagnosis.     

Covalent Functionalization of Multi‐walled Carbon Nanotubes with a Gadolinium Chelate for Efficient T1‐Weighted Magnetic Resonance Imaging

Given the promise of carbon nanotubes (CNTs) for photothermal therapy, drug delivery, tissue engineering, and gene therapy, there is a need for non‐invasive imaging methods to monitor CNT distribution and fate in the body. In this study, non‐ionizing whole‐body high field magnetic resonance imaging (MRI) is used to follow the distribution of water‐dispersible non‐toxic functionalized CNTs administrated intravenously to mice. Oxidized CNTs are endowed with positive MRI contrast properties by covalent functionalization with the chelating ligand diethylenetriaminepentaacetic dianhydride (DTPA), followed by chelation to Gd³⁺. The structural and magnetic properties, MR relaxivities, cellular uptake, and application for MRI cell imaging of Gd‐CNTs in comparison to the precursor oxidized CNTs are evaluated. Despite the intrinsic T₂ contrast of oxidized CNTs internalized in macrophages, the anchoring of paramagnetic gadolinium onto the nanotube sidewall allows efficient T₁ contrast and MR signal enhancement, which is preserved after CNT internalization by cells. Hence, due to their high dispersibility, Gd‐CNTs have the potential to produce positive contrast in vivo following injection into the bloodstream. The uptake of Gd‐CNTs in the liver and spleen is assessed using MRI, while rapid renal clearance of extracellular Gd‐CNTs is observed, confirming the evidences of other studies using different imaging modalities.     

Time‐Dependent T1–T2 Switchable Magnetic Resonance Imaging Realized by c(RGDyK) Modified Ultrasmall Fe3O4 Nanoprobes

To achieve the accurate diagnosis of tumor with the magnetic resonance imaging (MRI), nanomaterials‐based contrast agents are developed rapidly. Here, a tumor targeting nanoprobe of c(RGDyK) modified ultrasmall sized iron oxide is reported with high saturation magnetization and high T₁‐weighted imaging capability, attributed to a large number of paramagnetic centers on the surface of nanoprobes and rapid water proton exchange rate (inner sphere model), as well as strong superparamagnetism (outer sphere model). These nanoprobes could actively target and gradually accumulate at the tumor site with a time‐dependent T₁–T₂ contrast enhancement imaging effect. In in vivo MRI experiments, the nanoprobes exhibit the best T₁ contrast enhancement at 30 min after intravenous administration, followed by gradually vanishing and generating T₂ contrast enhancement with increasing time at tumor site. This is likely due to time‐dependent nanoprobes aggregation in tumor, in good agreement with in vitro experiment where aggregated nanoprobes display larger r₂/r₁ value (19.1) than that of the dispersed nanoprobes (2.8). This dynamic property is completely different from other T₁‐T₂ dual‐modal nanoprobes which commonly exhibit the T₁‐ and T₂‐weighted enhancement effect at the same time. To sum up, these c(RGDyK) modified ultrasmall Fe₃O₄ nanoprobes have significant potential to improve the diagnostic accuracy and sensitivity in MRI.     

Novel Redox‐Responsive Polymeric Magnetosomes with Tunable Magnetic Resonance Property for In Vivo Drug Release Visualization and Dual‐Modal Cancer Therapy

Monitoring of in vivo drug release from nanotheranostics by noninvasive approaches remains very challenging. Herein, novel redox‐responsive polymeric magnetosomes (PolyMags) with tunable magnetic resonance imaging (MRI) properties are reported for in vivo drug release monitoring and effective dual‐modal cancer therapy. The encapsulation of doxorubicin (DOX) significantly decreases PolyMags' T₂‐contrast enhancement and transverse relaxation rate R₂, depending on the drug loading level. The T₂ enhancement and R₂ can be recovered once the drug is released upon PolyMags' disassembly. T₂‐ and T₂*‐MRI and diffusion‐weighted imaging (DWI) are utilized to quantitatively study the correlation between MRI signal changes and drug release, and discover the MR tuning mechanisms. The in vivo drug release pattern is visualized based on such tunable MRI capability via monitoring the changes in T₂‐weighted images, T₂ and T₂* maps, and R₂ and R₂* values. Interestingly, the PolyMags possess excellent photothermal effect, which can be further enhanced upon DOX loading. The PolyMags are highly efficacious to treat breast tumors on xenograft model with tumor‐targeted photothermal‐ and chemotherapy, achieving a complete cure rate of 66.7%. The concept reported here is generally applicable to other micellar and liposomal systems for image‐guided drug delivery and release applications toward precision cancer therapy.     

Gadolinium‐Doped Iron Oxide Nanoprobe as Multifunctional Bioimaging Agent and Drug Delivery System

In this study, a high‐performance T₁–T₂ dual‐model contrast agent by gadolinium‐doped iron oxide nanoparticle (GION) is developed. Following its development, the application of this agent in vivo by combining doxorubicin (DOX) and folic acid (FA) (FA–GION–DOX) for targeted drug delivery to monitor cancer treatment is explored. GION showed transverse and longitudinal relaxivities up to 182.7 × 10^?3 and 7.87 × 10^?3m ^?1 s^?1, respectively, upon Gd/Fe ratio in GION at 1/4. DOX released from FA–GION–DOX is pH dependent and only kills cancer cell after FA receptor‐mediated internalization into the acidic environment of endosomes and lysosomes. Systemic delivery of FA–GION–DOX significantly inhibits the growth of tumors and shows good magnetic resonance enhancement in a human cervical cancer xenograft model. Thus, FA–GION–DOX has a potential application for the targeted and magnetic resonance imaging guided therapy of cervical cancer.     

Copolymer Networks Based on Poly(ω‐pentadecalactone) and Poly(ϵ‐caprolactone)Segments as a Versatile Triple‐Shape Polymer System

Thermo‐sensitive triple‐shape polymers can perform two consecutive shape changes in response to heat. These shape changes correspond to the recovery of two different deformations in reverse order, which were programmed previously at elevated temperature levels (T_mid and T_high) by the application of external stress. Recently, an AB copolymer network was described, which surprisingly exhibited a triple‐shape effect despite being programmed with only one deformation at T_high. Here it is explored whether a copolymer network system can be designed that enables a one‐step deformation process at ambient temperature (cold drawing) as a novel, gentle, and easy‐to‐handle triple‐shape‐creation procedure, in addition to the procedures reported to date, which generally involve deformation(s) at elevated temperature(s). A copolymer‐network system with two crystallizable polyester segments is synthesized and characterized, fulfilling two crucial criteria. These materials can be deformed at ambient temperature by cold drawing and show, even at T_high, which is above the melting points of both switching domains, elongation at break of up to 250%. Copolymer networks with PCL contents of 75 and 50 wt% show a triple‐shape effect after cold drawing with shape‐fixity ratios between 65% and 80% and a total‐shape‐recovery ratio above 97%. Furthermore, in these copolymer networks, the triple‐shape effect can be obtained after a one‐step deformation at T_high. Independent of the temperature at which the deformation is applied (ambient temperature or T_high), copolymer networks that have the same compositions show similar switching temperatures and proportioning of the recovery in two steps. The two‐step programming procedure enables a triple‐shape effect in copolymer networks for an even broader range of compositions. This versatile triple‐shape‐material system based on tailored building blocks is an interesting candidate material for applications in fixation systems or disassembling systems.