Efficient heterogeneous synthesis of nucleophilic carboxymethyl hydrazides of polysaccharides.

Nucleophilic moieties in polysaccharides (PS) with distinct higher reactivity compared with the hydroxy group are interesting for sustainable applications in chemistry, medicine, and pharmacy. An efficient heterogeneous method for the formation of such nucleophilic PS is described. Employing alcohols as slurry medium, protonated carboxymethyl (CM) PS and hydrazine hydrate are allowed to react at elevated temperatures. The CM derivatives of starch and pullulan can be transformed almost quantitatively to the corresponding hydrazides. The reaction is less efficient for CM dextrans and CM xylans. As slurry media, 2-propanol and ethanol were probed, and the results are compared with a homogeneous procedure performed in water. Overall, the heterogeneous procedure is superior compared with the homogeneous route. 2-Propanol is the best slurry medium investigated yielding PS hydrazides with the highest nitrogen content.

Comparative Study of a Series of 99mTc(CO)3 Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection.

Sentinel lymph node detection (SLND) is rapidly entering common practice in the management of patients with tumors. The introduction of mannose molecules to 99mTc-labeled dextrans, so far, showed that the sentinel node could trap these agents due to their recognition by the mannose receptors of lymph node macrophages. The current study aimed to synthesize, characterize, and biologically evaluate a series of mannosylated dextran derivatives labeled with 99mTc for potential use in SLND. The compounds were designed to have a dextran with a molecular weight of 10-500 kDa as a backbone, S-derivatized cysteines, efficient SNO chelators, and mannose moieties for binding to mannose receptors. They were successfully synthesized, thoroughly characterized using NMR techniques, and labeled with the fac-[99mTc(CO)3]+ synthon. Labeling with high yields and radiochemical purities was achieved with all derivatives. In vivo biodistribution and imaging studies demonstrated high uptake in the first lymph node and low uptakes in the following node and confirmed the ability to visualize the SLN. Among the compounds studied, 99mTc-D75CM demonstrated the most attractive biological features, and in combination with the high radiochemical yield and stability of the compound, its further evaluation as a new radiopharmaceutical for sentinel lymph node detection was justified.

Spatio-temporal control over destabilization of Pickering emulsions stabilized by light-sensitive dextran-based nanoparticles.

The implementation of light-sensitive Pickering emulsions with spatio-temporal responsiveness in advanced applications like drug-delivery, colloidal or reaction engineering would open new avenues. However, curiously, light-sensitive Pickering emulsions are barely studied in the literature and their biocompatibility and/or degradability scarcely addressed. Thus, their development remains a major challenge. As an original strategy, we synthesized light-sensitive nanoparticles based on biocompatible Poly(NitroBenzylAcrylate) grafted dextran (Dex-g-PNBA) to stabilize O/W Pickering emulsions. The produced emulsions were stable in time and could undergo time and space-controlled destabilization under light stimulus. Irradiation time and alkaline pH-control of the aqueous phase were proved to be the actual key drivers of destabilization. As the nanoparticles themselves were photolyzed under light stimulus, possible harmful effects linked to accumulation of nanomaterials should be avoided. In addition to UV light (365 nm), visible light (405 nm) was successfully used for the spatio-temporal destabilization of the emulsions, offering perspectives for life science applications.

Mussel-Inspired Bisphosphonated Injectable Nanocomposite Hydrogels with Adhesive, Self-Healing, and Osteogenic Properties for Bone Regeneration.

Injectable hydrogels have received much attention because of the advantages of simulation of the natural extracellular matrix, microinvasive implantation, and filling and repairing of complex shape defects. Yet, for bone repair, the current injectable hydrogels have shown significant limitations such as the lack of tissue adhesion, deficiency of self-healing ability, and absence of osteogenic activity. Herein, a strategy to construct mussel-inspired bisphosphonated injectable nanocomposite hydrogels with adhesive, self-healing, and osteogenic properties is developed. The nano-hydroxyapatite/poly(l-glutamic acid)-dextran (nHA/PLGA-Dex) dually cross-linked (DC) injectable hydrogels are fabricated via Schiff base cross-linking and noncovalent nHA-BP chelation. The chelation between bisphosphonate ligands (alendronate sodium, BP) and nHA favors the uniform dispersion of the latter. Moreover, multiple adhesion ligands based on catechol motifs, BP, and aldehyde groups endow the hydrogels with good tissue adhesion. The hydrogels possess excellent biocompatibility and the introduction of BP and nHA both can effectively promote viability, proliferation, migration, and osteogenesis differentiation of MC3T3-E1 cells. The incorporation of BP groups and HA nanoparticles could also facilitate the angiogenic property of endothelial cells. The nHA/PLGA-Dex DC hydrogels exhibited considerable biocompatibility despite the presence of a certain degree of inflammatory response in the early stage. The successful healing of a rat cranial defect further proves the bone regeneration ability of nHA/PLGA-Dex DC injectable hydrogels. The developed tissue adhesive osteogenic injectable nHA/PLGA-Dex hydrogels show significant potential for bone regeneration application.

Acid-Sensitive Supramolecular Nanoassemblies with Multivalent Interaction: Effective Tumor Retention and Deep Intratumor Infiltration.

It remains a conundrum to reconcile the contradiction between effective tumor retention and deep intratumor infiltration for nanotherapeutics due to the sophisticated drug delivery journey. Herein, we reported an acid-sensitive supramolecular nanoassemblies (DCD SNs) based on the multivalent host-gest inclusions of two polymer conjugates for conquering diverse physiological blockages and amplifying therapeutic efficacy. The multiple inclusions of repetitive units on the hydrophilic polymer backbone reinforced the binding affinity and induced robust self-assembly, ameliorating instability of the self-assemblies and facilitating to prolong the drug retention time. By virtue of the acid-sensitive Schiff base linkages, the supramolecular nanoassembly could respond to the unique tumor microenvironment (TME), dissociate, and transform into smaller particles (∼30 nm), thereby efficiently traversing the complicated extracellular matrix and irregular blood vessels to achieve deep intratumor infiltration. The acid-sensitive DCD SNs can absorb a large number of protons in the acidic lysosomal environment, causing the proton sponge effect, which was conducive to their escape from endolysosomes and accelerated lysosomal disruption, so that the active chemotherapeutic doxorubicin (DOX) could enter the nucleus well and exert severe DNA damage to induce apoptosis. This versatile supramolecular nanoplatform is anticipated to be a promising candidate to overcome the limitations of insufficient stability within the circulation and weak intratumor penetration.

One-pot synthesis of carboxymethyl-dextran coated iron oxide nanoparticles (CION) for preclinical fMRI and MRA applications.

Superparamagnetic iron-oxide nanoparticles are robust contrast agents for magnetic resonance imaging (MRI) used for sensitive structural and functional mapping of the cerebral blood volume (CBV) when administered intravenously. To date, many CBV-MRI studies are conducted with Feraheme, manufactured for the clinical treatment of iron-deficiency. Unfortunately, Feraheme is currently not available outside the United States due to commercial and regulatory constraints, making CBV-MRI methods either inaccessible or very costly to achieve. To address this barrier, we developed a simple, one-pot recipe to synthesize Carboxymethyl-dextran coated Iron Oxide Nanoparticles, namely, "CION", suitable for preclinical CBV-MRI applications. Here we disseminate a step-by-step instruction of our one-pot synthesis protocol, which allows CION to be produced in laboratories with minimal cost. We also characterized different CION-conjugations by manipulating polymer to metal stoichiometric ratio in terms of their size, surface chemistry, and chemical composition, and shifts in MR relaxivity and pharmacokinetics. We performed several proof-of-concept experiments in vivo, demonstrating the utility of CION for functional and structural MRI applications, including hypercapnic CO2 challenge, visual stimulation, targeted optogenetic stimulation, and microangiography. We also present evidence that CION can serve as a cross-modality research platform by showing concurrent in vivo optical and MRI measurement of CBV using fluorescent-labeled CION. The simplicity and cost-effectiveness of our one-pot synthesis method should allow researchers to reproduce CION and tailor the relaxivity and pharmacokinetics according to their imaging needs. It is our hope that this work makes CBV-MRI more openly available and affordable for a variety of research applications.

Acetalated dextran based nano- and microparticles: synthesis, fabrication, and therapeutic applications.

Acetalated dextran (Ac-DEX) is a pH-responsive dextran derivative polymer. Prepared by a simple acetalation reaction, Ac-DEX has tunable acid-triggered release profile. Despite its relatively short research history, Ac-DEX has shown great potential in various therapeutic applications. Furthermore, the recent functionalization of Ac-DEX makes versatile derivatives with additional properties. Herein, we summarize the cutting-edge development of Ac-DEX and related polymers. Specifically, we focus on the chemical synthesis, nano- and micro-particle fabrication techniques, the controlled-release mechanisms, and the rational design Ac-DEX-based of drug delivery systems in various biomedical applications. Finally, we briefly discuss the challenges and future perspectives in the field.

Antifouling Antioxidant Zwitterionic Dextran Hydrogels as Wound Dressing Materials with Excellent Healing Activities.

Hydrogels as wound dressings have received great attention in recent years. It is highly important yet challenging to develop hydrogel dressings that are biocompatible and that can promote wound healing by lowering the risk of inflammatory responses. In this work, we designed and prepared zwitterionic dextran-based hydrogels using carboxybetaine dextran (CB-Dex) and sulfobetaine dextran (SB-Dex) as raw materials, respectively. The efficacy of CB-Dex and SB-Dex hydrogels in promoting wound recovery was evaluated using a mouse skin wound model. Results suggested that the zwitterionic dextran wound dressings showed a faster healing rate than natural dextran hydrogel and a commercial wound dressing (Duoderm film) due to their excellent protein resistance and capacity to scavenge free hydroxyl radicals. In addition, both CB-Dex and SB-Dex hydrogel wound dressings showed excellent cytocompatibility with NIH3T3 and L929 cells, as well as antibacterial adhesion against Staphylococcus aureus and Escherichia coli. Furthermore, both zwitterionic hydrogels demonstrated self-healing properties and can be stretched to adapt to irregular full-thickness wound beds. More importantly, they can be removed from the wound site painlessly by washing with normal saline. Overall, this work provided a new pathway to fabricate multifunctional polysaccharide hydrogels for wound treatment and pain relief when changing wound dressings.

Cationised dextran and pullulan modified with diethyl aminoethyl methacrylate for gene delivery in cancer cells.

This work describes the synthesis and characterisation of cationised dextran and pullulan modified with diethyl aminoethyl methacrylate (DEAEM) for gene delivery in cancer cells. To dextran and pullulan, PEI was conjugated to impart cationicity. These cationised polysaccharides were then modified with DEAEM monomer via Michael addition reaction and synthesised four different derivatives viz DPD I, DPD II, PPD I and PPD II. These vectors form nanocomplexes with DNA exhibiting positive zeta potential. These nanoplexes are cytocompatible in C6, HeLa and L929 cells. Transfection efficiency of these vectors was evaluated using p53 plasmid which demonstrated good transfection in cancer cells (C6 and HeLa) alone. Biodistribution studies of DPD II and PPD II in BALB/c mice shows its tendency to accumulate in liver tissue and not in any vital organs like brain, lungs and heart. In addition, these derivatives also exhibit good renal clearance.

Synthesis, Characterization, and Application of Superparamagnetic Iron Oxide Nanoprobes for Extrapulmonary Tuberculosis Detection.

A molecular imaging probe comprising superparamagnetic iron oxide (SPIO) nanoparticles and Mycobacterium tuberculosis surface antibody (MtbsAb) was synthesized to enhance imaging sensitivity for extrapulmonary tuberculosis (ETB). An SPIO nanoprobe was synthesized and conjugated with MtbsAb. The purified SPIO-MtbsAb nanoprobe was characterized using TEM and NMR. To determine the targeting ability of the probe, SPIO-MtbsAb nanoprobes were incubated with Mtb for in vitro imaging assays and injected into Mtb-inoculated mice for in vivo investigation with magnetic resonance (MR). The contrast enhancement reduction on magnetic resonance imaging (MRI) of Mtb and THP1 cells showed proportional to the SPIO-MtbsAb nanoprobe concentration. After 30 min of intravenous SPIO-MtbsAb nanoprobe injection into Mtb-infected mice, the signal intensity of the granulomatous site was enhanced by 14-fold in the T2-weighted MR images compared with that in mice receiving PBS injection. The MtbsAb nanoprobes can be used as a novel modality for ETB detection.

Reactive oxygen species-activatable camptothecin polyprodrug based dextran enhances chemotherapy efficacy by damaging mitochondria.

Low loading capacity, poor accumulation rate and weak permeability at tumor sites have been identified as the critical barriers for anti-cancer nanomedicines (ANMs). We herein reported a reactive oxygen species (ROS)-activatable ANM of dextran-b-P(CPTMA-co-OEGMA) (DCPT). It aimed to meet the above challenges for improving the therapeutic efficiency of chemotherapy. In this system, camptothecin (CPT) was selected as a chemotherapy drug and poly(ethylene glycol)methyl ether methacrylate (OEGMA) played the role of a hydrophilic block to enhance the water solubility of polyprodrug micelles. At high ROS levels in the tumor microenvironment, the micelles could be disassembled, and simultaneously, the anti-cancer drug of CPT would be released from the DCPT micelles. The 4T1-tumor growth would be greatly inhibited by these two DCPT polyprodrugs, with outstanding in vivo biosafety. The results of both in vitro and in vivo studies indicated the superior therapeutic effects of DCPT. The rational design of polyprodrug nanomedicines may serve as a promising strategy for the development of tumor microenvironment-responsive ANMs, thus improving chemotherapy efficacy.

Glucose-Responsive Nanoparticles for Rapid and Extended Self-Regulated Insulin Delivery.

To mimic native insulin activity, materials have been developed that encapsulate insulin, glucose oxidase, and catalase for glucose-responsive insulin delivery. A major challenge, however, has been achieving the desired kinetics of both rapid and extended release. Here, we tune insulin release profiles from polymeric nanoparticles by altering the degree of modification of acid-degradable, acetalated-dextran polymers. Nanoparticles synthesized from dextran with a high acyclic acetal content (94% of residues) show rapid release kinetics, while nanoparticles from dextran with a high cyclic acetal content (71% of residues) release insulin more slowly. Thus, coformulation of these two materials affords both rapid and extended glucose-responsive insulin delivery. In vivo analyses using both streptozotocin-induced type 1 diabetic and healthy mouse models indicate that this delivery system has the ability to respond to glucose on a therapeutically relevant time scale. Importantly, the concentration of human insulin in mouse serum is enhanced more than 3-fold with elevated glucose levels, providing direct evidence of glucose-responsiveness in animals. We further show that a single subcutaneous injection provides 16 h of glycemic control in diabetic mice. We believe the nanoparticle formulations developed here may provide a generalized strategy for the development of glucose-responsive insulin delivery systems.

Self-assembling Dextran prodrug for redox- and pH-responsive co-delivery of therapeutics in cancer cells.

Self-assembling prodrug containing pH- and redox-responsive functional groups was prepared by covalent conjugation of Doxorubicin (Dox) and lipoic acid (LA) to a polyaldehyde Dextran (PAD). The resultant amphiphilic DoxPADLA forms, in a single step, hemocompatible vesicular systems able to respond to intracellular signals without using external crosslinking agents. Camptothecin (CPT) was encapsulated exploiting the hydrophobic interactions with the vesicle membrane, and release experiments, carried out in media mimicking the physiological and endolysosomial compartments, in the absence or presence of Glutathione, proved the ability of the system to modulate drug release in relation to the variation of pH and redox potential. Cytotoxicity assays and confocal experiments demonstrated the efficacy of the vesicle formulation in enhancing the synergistic anticancer effect of the delivered Dox and CPT and a rapid and significant internalization of the carrier in cancer cells.

4-Sulfonatocalixarene-induced nanoparticle formation of methylimidazolium-conjugated dextrans: Utilization for drug encapsulation.

Methylimidazolium side groups were grafted via ether linkage to dextran and the self-assembly of these polymers with 4-sulfonato-calix[n]arenes (SCXn) was studied in aqueous solutions. Dynamic light scattering and zeta potential measurements revealed the mixing ratio ranges of the constituents where stable nanoparticles could be created. The macrocycle size of SCXn and the molecular mass of the polymer barely affected the nanoparticle diameter, but the lowering of the imidazolium degree of substitution substantially diminished the stability of the associates. The pH change from neutral to acidic also unfavourably influenced the self-organization owing mainly to the decrease of the SCXn charge. Cryogenic transmission electron microscopy images proved the spherical morphology of the nanoproducts in which the stoichiometry of the constituents was always close to the one corresponding to charge compensation. The flexible and positively charged dextran-chains are compacted by the polyanionic SCXn. Coralyne, a pharmacologically important alkaloid was efficiently embedded by self-assembly in the produced nanoparticles reaching 99% association efficiency.

Biocompatible conductive hydrogels based on dextran and aniline trimer as electro-responsive drug delivery system for localized drug release.

Dextran with good biocompatibility and degradability shows great potentials for drug delivery and tissue engineering applications. Electro-responsive drug delivery system can provide on-demand and localized drug release. However, dextran-based conductive hydrogel with electrical stimuli responsiveness as drug delivery system has not been reported. Herein, we designed and fabricated a kind of biocompatible biodegradable conductive hydrogel system with the property of electro-responsiveness as a new smart drug delivery system for localized drug release. These series of hydrogels were synthesized by mixing dextran and electroactive aniline trimer with hexamethylene diisocyanate as crosslinker to form hydrogel network. These series of hydrogels exhibited stable rheological property and controllable swelling ratio. These hydrogels showed good conductivity and desirable electric stimuli ability to control drug release. Furthermore, this kind of hydrogel was controlled by external electrical stimuli to generate a kind of "on-off" precise drug release system. When extra voltage was applied, they released more drug intelligently and less drug molecule without external stimuli. The hydrogel showed good cytocompatibility and in vivo biocompatibility by using H&E staining and Toluidine blue staining. All together, these results indicated that these series of biocompatible conductive dextran-based hydrogels were promising candidates as smart drug delivery systems in future biomedical field.

Amino Acid-Substituted Dextran-Based Non-Viral Vectors for Gene Delivery.

To form bio-inspired non-viral vectors for DNA delivery, the polysaccharide dextran is allowed to react with Boc-amino protected amino acids glycine, ß-alanine, and L-lysine activated with 1,1'-carbonyldiimidazole and subsequent dextran ester deprotection. A library of such dextran esters is made available to investigate the relationship between polymer structure, complex formation, stability, toxicity, and transfection. Only dextran esters of ß-alanine and L-lysine are able to efficiently interact with DNA as shown by dye exclusion assays, to form nanosized complexes (70-110 nm) with positive zeta potential. With increasing substitution degree and complex charge ratios, the L-lysine esters accomplish more effective binding and protection of DNA against enzymatic degradation than ß-alanine esters. However, luciferase reporter gene assays reveal higher transfection for ß-alanine than for L-lysine esters due to a more effective DNA release and better suited buffing area of the amino groups triggering the endosomal release. Conclusively, ß-alanine-substituted dextran derivatives may serve as promising non-viral vectors.

A bright blue fluorescent dextran for two-photon in vivo imaging of blood vessels.

Fluorescence-based in vivo imaging is one of the most important tools for monitoring of biological processes in cells and tissues of live animal models. Fluorescence imaging agents have also been used to monitor the microcirculation. Tracking microcirculation of the blood is vital to gain further insight into various vascular disease-related anomalies within the human body. As monitoring of vascular circulation is performed with visualization of both immune cells and pathogens, which are mainly labelled with red and green, the favorable color option for blood vessels could be blue. However, currently available blueish color-labeled agents for vascular monitoring is generally confronted with quick bleaching, because of its short excitation and emission wavelengths. Hereby, what we propose in this report is a newly generated bright blue fluorescent dextran, named HCD-70K that monitors the blood vessels using blue and inter-compatible typical fluorescent materials. DBCO-functionalized dextran-70K was fabricated with hydroxy-coumarin dye via metal-free bioorthogonal click chemistry, and generated HCD-70K, which can flow within the blood vessel and decipher the whole structure of the blood vessel successfully. The synthesis, spectroscopic analysis, and quantum chemical calculations were conducted. Using two-photon microscopy, efficient deep in vivo blood vessel imaging of a mouse model revealed exceptional bio-imaging capabilities of the HCD-70K and consequently it provided a promising opportunity for efficient vascular visualization in various research areas.

Polycarboxylated Dextran as a Multivalent Linker: Synthesis and Target Recognition of the Antibody-Nanoparticle Bioconjugates in PBS and Serum.

Nanoparticles (NPs) functionalized with antibodies on their surface are used in a wide range of research applications. However, the bioconjugation chemistry between the antibodies and the surface of nanoparticles can be very challenging, often accompanied by several undesired effects such as nanoparticle aggregation, antibody denaturation, or poor target recognition of the surface-bound antibodies. Here, we report on a synthesis of fluorescent silica nanoparticle-antibody (NP-Ab) conjugates, in which polycarboxylated dextran is used as the multivalent linker. First, we present a synthetic methodology to prepare polycarboxylated dextrans with molecular weights of 6, 40, and 70 kDa. Second, we used water-soluble, polycarboxylated dextrans as a multivalent spacers/linkers to immobilize antibodies onto fluorescent silica nanoparticles. The prepared NP-Ab conjugates were tested in a direct binding assay format in both phosphate-buffered saline buffer and whole serum to investigate the role of the spacer/linker in the capacity of the NP-Ab to specifically recognize their target in "clean" and also in complex media. We have compared the dextran conjugates with two standards: (a) NP-Ab with antibodies attached on the surface of nanoparticles through the classical physical adsorption method and (b) NP-Ab where an established poly(amidoamine) (PAMAM) dendrimer was used as the linker. Our results showed that the polycarboxylated 6 kDa dextran facilitates antibody immobilization efficiency of nearly 92%. This was directly translated into the improved molecular recognition of the NP-Ab, which was measured by a direct binding assay. The signal-to-noise ratio in buffered solution for the 6 kDa dextran NP-Ab conjugates was 81, nearly 3 times higher than that of PAMAM G4.5 conjugates and 9 times higher than the physically adsorbed NP-Ab sample. In whole serum, the effect of 6 kDa dextran was more hindered due to the formation of protein corona but the signal-to-noise ratio was at least double that of the physically adsorbed NP-Ab conjugates.

Chlorin e6-Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Nanoclusters as a Theranostic Agent for Dual-Mode Imaging and Photodynamic Therapy.

Photodynamic therapy (PDT) is an approved modality for the treatment of various types of maligancies and diseased states. However, most of the available photosensitizers (PS) are highly hydrophobic, which limits their solubility and dispersion in biological fluids and can lead to self-quenching and sub-optimal therapeutic efficacy. In this study, chlorin e6 (Ce6)-coated superparamagnetic iron oxide nanoparticle (SPION) nanoclusters (Ce6-SCs) were prepared via an oil-in-water emulsion. The physical-chemical properties of the Ce6-SCs were systematically evaluated. Dual-mode imaging and PDT was subsequently performed in tumor-bearing mice. Chlorin e6 is capable of solubilizing hydrophobic SPION into stable, water-soluble nanoclusters without the use of any additional amphiphiles or carriers. The method is reproducible and the Ce6-SCs are highly stable under physiological conditions. The Ce6-SCs have an average diameter of 92 nm and low polydispersity (average PDI < 0.2). Encapsulation efficiency of both Ce6 and SPION is ≈100%, and the total Ce6 payload can be as high as 56% of the total weight (Ce6 + Fe). The Ce6-SCs localize within tumors via enhanced permeability and retention and are detectable by magnetic resonance (MR) and optical imaging. With PDT, Ce6-SCs demonstrate high singlet oxygen generation and produce a significant delay in tumor growth in mice.

Synthesis and characterization of magnetic dextran nanogel doped with iron oxide nanoparticles as magnetic resonance imaging probe.

Magnetic hybrid nanogels composed of magnetic nanoparticles and polymer hydrogel matrix have drawn much attention because of their unique superparamagnetic properties and biocompatibility as biomaterials. In this study, a facile method was developed for the preparation of iron oxide nanoparticle-loaded magnetic dextran nanogel as magnetic resonance imaging (MRI) probe. Water soluble superparamagnetic iron oxide nanocrystals (Fe3O4) was pre-synthesized and physically doped into a Schiff base-containing dextran nanogel formed using W/O microemulsion as nanoreactor. Magnetic dextran nanogel (Fe3O4@Dex) with particle size of 300-1000 nm was obtained with multiple Fe3O4 nanoparticles randomly encapsulated in the hydrogel networks. Magnetization and T2 relaxivity study shows that the resulted magnetic nanogel has similar superparamagneitc behaviors with single Fe3O4 nanocrystals, and relatively higher T2 relaxivity (277.2 mMFe-1·s-1) as MRI probe. Notably, Schiff base linkages and aldehyde groups on the dextran hydrogel matrix endow the magnetic nanogel with pH-sensitiveness and reactive groups for further modifications, which make the magnetic dextran nanogel a promising nanoplatform as MRI-guided drug delivery system with acid environment-responsiveness.