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We present a facile particle-based cell manipulation method using acoustic radiation forces. In this work, we selected several representative particles including poly(lactic-co-glycolic acid) (PLGA) microspheres, silica-coated magnetic microbeads, polydimethylsiloxane (PDMS) microspheres and investigated the responses of these particle systems to ultrasonic standing waves (USWs) in a microfluidic chip. We show that depending on the nature (positive or negative acoustic contrast factors) of the particles, these particle systems display different alignment behaviors along the microfluidic channel under USWs. Specifically, PLGA microspheres and silica-coated magnetic microbeads are able to be aligned in the middle of the microfluidic channel, while PDMS microspheres are translocated to the side walls of the channel, which is beneficial for cell trapping and manipulation. Further results demonstrate that the functional PDMS microspheres with a negative acoustic contrast factor can be used to trap cells to the pressure antinodes in the acoustofluidic chip. Cell viability tests reveal that the ultrasonic manipulation does not exert any harmful effect to the cells. This acoustic-based particle and cell manipulation technique may hold a great promise for the development of rapid, noninvasive, continuous assays for detecting of cells and separation of biological samples.

Development of multifunctional nanoplatforms for tumor multimode imaging and therapy is of great necessity. Herein, we report a new type of Au nanostar (NS)-coated, perfluorohexane (PFH)-encapsulated hollow mesoporous silica nanocapsule (HMS) modified with poly(ethylene glycol) (PEG) for tumor multimode ultrasonic (US)/computed tomography (CT)/photoacoustic (PA)/thermal imaging, and photothermal therapy (PTT). HMSs were first synthesized, silanized to have thiol surface groups, and coated with gold nanoparticles via a Au-S bond. Followed by growth of Au NSs on the surface of the HMSs, encapsulation of PFH in the interior of the HMSs, and surface conjugation of thiolated PEG, multifunctional HMSs@Au-PFH-mPEG NSs (for short, HAPP) were formed and well-characterized. We show that the HAPP are stable in a colloidal manner and noncytotoxic in the studied range of concentrations, possess multimode US/CT/PA/thermal imaging ability, and can be applied for multimode US/CT/PA/thermal imaging of tumors in vivo after intravenous or intratumoral injection. Additionally, the near-infrared absorption property of the HAPP enables the use of the HAPP for photothermal ablation of cancer cells in vitro and a tumor model in vivo after intratumoral injection. The developed multifunctional HAPP may be used as a novel multifunctional theranostic nanoplatform for tumor multimode imaging and PTT.

We report the facile synthesis of polyaniline (PANI)-loaded γ-polyglutamic acid (γ-PGA) nanogels (NGs) for photoacoustic (PA) imaging-guided photothermal therapy (PTT) of tumors. In this work, γ-PGA NGs were first formed via a double emulsion approach, followed by crosslinking with cystamine dihydrochloride (Cys) via 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride coupling chemistry. The formed γ-PGA/Cys NGs were employed as a nanoreactor to load aniline monomers via an electrostatic interaction for subsequent in situ polymerization in the presence of ammonium persulfate. The resulting γ-PGA/Cys@PANI NGs were thoroughly characterized. It is shown that the γ-PGA/Cys@PANI NGs with an average size of 71.9 nm are dispersible in water, colloidally stable, and cytocompatible and hemocompatible in the concentration range studied. The strong near-infrared (NIR) absorbance renders the NGs with good PA imaging contrast enhancement and photothermal conversion properties. With these excellent properties and biocompatibility, the developed γ-PGA/Cys@PANI NGs are able to be used for PA imaging-guided PTT of cancer cells in vitro and a xenografted tumor model in vivo. This unique theranostic nanoplatform may be further loaded with other imaging or therapeutic elements, or modified with targeting ligands, thereby providing a ubiquitous platform for multimode imaging and combinational therapy of different biosystems.

We report the synthesis and characterization of antifouling zwitterion carboxybetaine acrylamide (CBAA)-modified dendrimer-entrapped gold nanoparticles (Au DENPs) for enhanced CT imaging applications. The CBAA-modified nanodevice displays a better protein resistance property, less macrophage cellular uptake and liver accumulation, and longer blood half-delay time than the PEGylated counterpart material, thereby enabling enhanced blood pool, lymph node, and tumor CT imaging.

RNA interference (RNAi) has been considered as a promising strategy for effective treatment of cancer. However, the easy degradation of small interfering RNA (siRNA) limits its extensive applications in gene therapy. For safe and effective delivery of siRNA, a novel vector system possessing excellent biocompatibility, highly efficient transfection efficiency and specific targeting properties has to be considered. In this study, we report the use of polyethyleneimine (PEI)-entrapped gold nanoparticles (Au PENPs) modified with an arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide via a poly(ethylene glycol) (PEG) spacer as a vector for Bcl-2 (B-cell lymphoma-2) siRNA delivery to glioblastoma cells. The synthesized Au PENPs were well characterized. The efficiency of siRNA delivery was appraised by flow cytometry, confocal microscopy imaging, and the protein expression level. Our results revealed that the Au PENPs were capable of delivering Bcl-2 siRNA to glioblastoma cells with an excellent transfection efficiency, leading to specific gene silencing in the target cells (22% and 25.5% Bcl-2 protein expression in vitro and in vivo, respectively) thanks to the RGD peptide-mediated targeting pathway. The designed RGD-targeted Au PENPs may hold great promise to be used as a novel vector for specific cancer gene therapy applications.

Nanoparticles (NPs) have provided new opportunities to diagnose and treat various types of cancers, while it still remains a great challenge to develop novel and effective nanoscale platforms for these applications. In this study, we report a facile hydrothermal route to generate size- and shape-controlled gadolinium hydroxide (Gd(OH)3) NPs and polyethylenimine (PEI)-stabilized Gd(OH)3@Au core/shell nanostars (NSs). We show that Gd(OH)3 NPs with controlled size and shape can be synthesized through varying the stabilizer, reaction time and solvent. The formed Gd(OH)3 nanorods can be transformed into rice-shaped counterparts in the presence of trisodium citrate dehydrate. Furthermore, the introduction of PEI does not alter the morphology, rather have an impact on the size of the products. This facile synthetic route can also be utilized to synthesize Gd(OH)3@Au nanocomposite particles that can act as seeds to form Gd(OH)3@Au NSs in the Au growth solution. Further modification of PEI endows these NSs with excellent water-solubility and colloidal stability. Due to the strong surface plasmon resonance peak in the near-infrared region, the as-prepared Gd(OH)3@Au-PEI NSs display a high photothermal conversion efficiency under laser irradiation. The developed size- and shape-controlled Gd(OH)3 NPs and PEI-stabilized Gd(OH)3@Au core/shell NSs may be further developed as theranostic agents for various biomedical applications.

We report the synthesis and characterization of lactobionic acid-modified multifunctional polyethyleneimine-entrapped gold nanoparticles for targeted dual mode computed tomography/magnetic resonance imaging. The nanodevice displays good X-ray attenuation properties, good r1 relaxivity, and hepatocellular carcinoma targeting specificity, and can be used for targeted CT/MR imaging of hepatocellular carcinoma in vitro and in vivo.

The development of cost-effective targeted drug delivery systems for cancer chemotherapy still remains a great challenging task. Here, we describe the synthesis and characterization of multifunctional polyethylenimine (PEI) as an effective vehicle to load an anticancer drug doxorubicin (DOX) for in vivo targeted cancer therapy. In this study, PEI was sequentially conjugated with polyethylene glycol (PEG) monomethyl ether, PEGylated folic acid (FA), and fluorescein isothiocyanate (FI). This was followed by the acetylation of the remaining PEI surface amines. The formed FA-targeted multifunctional PEI (FA-mPEI) was used as a vehicle to encapsulate DOX. We show that the formed FA-mPEI/DOX complexes with each PEI encapsulating 6.9 DOX molecules are water dispersible and can sustainably release DOX in a pH-dependent manner, showing a higher release rate under acidic pH conditions than under physiological pH conditions. Furthermore, the complexes display specific therapeutic efficacy to cancer cells in vitro and a subcutaneous tumor model in vivo, and have good organ compatibility. The designed multifunctional PEI may be used as an effective vehicle for targeted cancer chemotherapy.

The design of pH-sensitive supramolecular drug delivery systems for efficient antineoplastic drug delivery remains a huge challenge. Herein, we describe the development of pH-responsive core–shell tecto dendrimers (CSTDs) formed using benzimidazole (BM)-modified generation 3 (G3) poly(amidoamine) (PAMAM) dendrimers (G3.NHAc-BM) as a shell and β-cyclodextrin (CD)-modified G5 PAMAM dendrimers (G5.NHAc-CD) as a core. By virtue of the host–guest recognition and pH-responsiveness of BM/β-CD assembly, the pH-sensitive supramolecular CSTDs of G5.NHAc-CD/BM-G3.NHAc were formed and adopted to encapsulate the anticancer drug doxorubicin (DOX) via hydrophobic interactions for pH-responsive drug delivery applications. The synthesis of dendrimer derivatives and the loading of the DOX were well characterized via different methods. We show that the encapsulated DOX can be released in a sustained manner with a rapid release speed under a slightly acidic pH condition (pH < 6), which is similar to acidic tumor microenvironment. The enhanced intracellular release of DOX and improved anticancer activity of the drug-loaded pH-responsive CSTDs were demonstrated and compared with the control CSTDs formed without pH-responsiveness through flow cytometry and viability assays of cancer cells. Furthermore, the pH-sensitive CSTDs also showed efficient drug penetration and growth inhibition of three-dimensional tumor spheroids owing to the faster DOX release in an acidic pH environment. The pH-sensitive G5.NHAc-CD/BM-G3.NHAc CSTDs may be employed as a valuable intelligent delivery system for various anticancer drugs.

Zwitterions are a class of unique molecules that can be modified onto nanomaterials to render them with antifouling properties. Here we report a thorough NMR investigation of dendrimers modified with zwitterions in terms of their structure, hydrodynamic size, and diffusion time in aqueous solution. In this present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5) were partially decorated with carboxybetaine acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively with different modification degrees. The formed zwitterion-modified G5 dendrimers were characterized using NMR techniques. We show that the zwitterion modification leads to increased G5 dendrimer size in aqueous solution, suggesting that the modified zwitterions can form a hydration layer on the surface of G5 dendrimers. In addition, the hydrodynamic sizes of G5 dendrimers modified with different zwitterions but with the same degree of surface modification are discrepant depending on the type of zwitterions. The present study provides a new physical insight into the structure of zwitterion-modified G5 dendrimers by NMR techniques, which is beneficial for further design of different biomedical applications.

Nanomaterials have been ubiquitously employed as platforms to load imaging agents for cancer diagnosis. In general, the majority of nanomaterials are accumulated in the reticuloendothelial system (RES)-associated organs such as liver, spleen, and lung after systemic administration. Although the adopted strategy used to modify nanomaterials with polyethylene glycol (PEG) has relieved this problem to some extent, challenges still remain for further clinical applications. Recently, nanomaterials with zwitterionic surface modification have been found to have a better antifouling property than those with PEGylation modification. This Topical Review reports the recent progress in the development of zwitterion-modified nanomaterials for improved cancer cell diagnosis, including zwitterionic modification of hybrid nanoparticles for enhanced fluorescence, computed tomography (CT), magnetic resonance (MR), and dual-mode imaging of cancer cells, and the zwitterionic modification of nanofibers for specific capture of circulating tumor cells with improved capture purity and efficiency. Challenges and future perspectives in this particular field are also discussed.

Nanogels (NGs) are 3-dimensional (3D) networks composed of hydrophilic or amphiphilic polymer chains, allowing for effective and homogeneous encapsulation of drugs, genes, or imaging agents for biomedical applications. Polyethylenimine (PEI), possessing abundant positively charged amine groups, is an ideal platform for the development of NGs. A variety of effective PEI-based NGs have been designed and much effort has been devoted to study the relationship between the structure and function of the NGs. In particular, PEI-based NGs can be prepared either using PEI as the major NG component or using PEI as a crosslinker. This review reports the recent progresses in the design of PEI-based NGs for gene and drug delivery and for bioimaging applications with a target focus to tackle the diagnosis and therapy of cancer.

We demonstrate a novel serum-enhanced gene delivery approach using zwitterion-functionalized dendrimer-entrapped gold nanoparticles (Au DENPs) as a non-viral vector for inhibition of cancer cell metastasis in vitro. Poly(amidoamine) dendrimers of generation 5 decorated with zwitterion carboxybetaine acrylamide (CBAA) and lysosome-targeting agent morpholine (Mor) were utilized to entrap gold NPs. We show that both Mor-modified and Mor-free Au DENPs are cytocompatible and can effectively deliver plasmid DNA encoding different reporter genes to cancer cells in medium with or without serum. Strikingly, due to the antifouling property exerted by the attached zwitterion CBAA, the gene delivery efficiency of Mor-modified Au DENPs and the Mor-free Au DENPs in the serum-containing medium are 1.4 and 1.7 times higher than the corresponding vector in serum-free medium, respectively. In addition, the Mor-free vector has a better gene expression efficiency than the Mor-modified one although the Mor modification enables the polyplexes to have enhanced cancer cell uptake. Wound healing and hypermethylated in cancer 1 (HIC1) protein expression assay data reveal that the expression of HIC1 gene in cancer cells enables effective inhibition of cell migration. Our findings suggest that the created zwitterion-functionalized Au DENPs may be employed as a powerful vector for serum-enhanced gene therapy of different diseases. STATEMENT OF SIGNIFICANCE: One major challenge in the non-viral gene delivery system is that the strong interaction between serum protein and the positively charged vector/gene polyplexes neutralize the positive charge of the polyplexes and form possible protein corona, thereby significantly reducing their cellular uptake efficiency and subsequent gene transfection outcome. Here we demonstrate the conceptual advances in the serum-enhanced gene delivery using zwitterionic modification of polycationic poly(amidoamine) (PAMAM) dendrimer-entrapped gold nanoparticles (Au DENPs). We demonstrate that partial zwitterionic modification of Au DENPs is able to confer them with antifouling property to resist serum protein adsorption. Hence the vector/DNA polyplexes are able to maintain their positive potentials and small hydrodynamic size in the serum environment, where serum solely play the role as a nutrition factor for enhanced gene delivery. We demonstrate that partial modification of zwitterion carboxybetaine acrylamide (CBAA) and morpholine (Mor) onto the surface Au DENPs renders the vector with both antifouling property and lysosome targeting ability, respectively. The generated functional Au DENPs can compact pDNA to form polyplexes that enable serum-enhanced gene expression. In particular, once complexed with hypermethylated in cancer 1 (HIC1) gene, the polyplexes can significantly inhibit cancer cell migration and metastasis.

Chemokine receptor-4 (CXCR4) has been demonstrated to be overexpressed in glioma cells and associated with poor survival. In the present study, we designed and synthesized

Design of dual mode or multimode contrast agents or nanoplatforms with antifouling properties is crucial for improved cancer diagnosis since the antifouling materials are able to escape the clearance of the reticuloendothelial system with improved pharmacokinetics. Herein, we present the creation of zwitterionic gadolinium(III) (Gd(III))-complexed dendrimer-entrapped gold nanoparticles (Au DEN) for enhanced dual mode computed tomography (CT)/magnetic resonance (MR) imaging of lung cancer metastasis. In the present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 were partially decorated with carboxybetanie acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively at different degrees, then used to entrap Au NPs within their interiors, and finally acetylated to cover their remaining amine termini. Through protein resistance, macrophage cellular uptake, and pharmacokinetics assays, we show that zwitterionic Au DEN modified with 1,3-PS exhibit the best antifouling property with the longest half-decay time (37.07 h) when compared to the CBAA- and MPC-modified Au DEN. Furthermore, with the optimized zwitterion type, we then prepared zwitterionic Gd(III)-loaded Au DEN modified with arginine-glycine-aspartic acid peptide for targeted dual mode CT/MR imaging of a lung cancer metastasis model. We disclose that the designed multifunctional Au DEN having an Au core size of 2.7 nm and a surface potential of 7.6 ± 0.9 mV display a good X-ray attenuation property, relatively high r

We present the design of antifouling zwitterion-functionalized manganese oxide (Mn3O4) nanoparticles (NPs) modified with folic acid (FA) for targeted tumor magnetic resonance (MR) imaging. In the c...

Core-shell tecto dendrimers (CSTDs) are a class of superstructured dendrimeric nanoconstructs with similar structural characteristics and biomedical performances to the high-generation dendrimers that can be decorated with zwitterions to be availed of good antifouling properties for different biomedical applications. Characterization of the CSTD-based dendrimeric derivatives remains to be a great challenge. Here, we attempted to utilize nuclear magnetic resonance (NMR) technologies to investigate the structure and hydrodynamic size of CSTDs functionalized with zwitterionic carboxybetaine acrylamide (CBAA) and confirmed their antifouling property through protein resistance assay. In this study, we initially prepared CSTDs by supramolecular assembly of beta-cyclodextrin (β-CD)-modified generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers as cores and adamantane (Ad)-decorated G3 PAMAM dendrimers as shells, and then partially modified the CSTD terminal amines with CBAA. The dendrimeric products were thoroughly characterized. Our results show that the obtained CSTDs display strong correlation signals between the Ad and β-CD protons in the two-dimensional NMR spectrum, indicating the strong host-guest interaction existing between G3-Ad and G5-CD in the structure of CSTDs. Diffusion NMR measurements reveal that the hydrodynamic diameter of CSTDs is smaller after partial CBAA surface modification, possibly due to the tightened molecular volume after zwitterionic modification. Lastly, the CBAA-modified CSTDs were demonstrated to have good antifouling property through protein resistance assay. Our findings provide a new strategy to study the framework of the developed CSTDs and CBAA-modified CSTDs, facilitating their further design and surface modification for various biomedical applications.

Design of intelligent hybrid nanoparticles that can integrate diagnosis and therapy components plays an important role in the field of nanomedicine. Poly(amidoamine) (PAMAM) dendrimers possessing a unique architecture and tunable functional groups have been widely developed for various biomedical applications. Carbon dots (CDs) are considered as a promising fluorescence probe or drug delivery system due to their stable fluorescence property and excellent biocompatibility. The distinctive merits of PAMAM dendrimers and CDs are amenable for them to be constructed as perfect nanohybrids for different biomedical applications, in particular for cancer nanomedicine. Here, the recent advances in the construction of PAMAM dendrimer/CD nanohybrids for diverse biomedical applications, in particular for sensing and cancer theranostics are summarized. Finally, the future perspectives of the PAMAM dendrimer/CD nanohybrids are also briefly discussed.

The immune system is a network of defense mechanisms, made up of organs, tissues, and diversified immune cells, with the mission of detecting and attacking invading pathogens. Cancer immunotherapy, which triggers effective anticancer responses via the regulation or alteration of the immune system, has emerged as one novel powerful strategy to fight cancer in contrast to the conventional resorts including surgery, radiotherapy, and chemotherapy. With the recent rapid development of nanomedicine, more opportunities are afforded to achieve highly efficient cancer immunotherapy. Dendrimers present a category of nano‐sized macromolecules with highly‐branched three‐dimensional structure, favorable biocompatibility, and tunable surface functionality. Various kinds of functionalized dendrimers and dendrimer‐based nanohybrids have been explored in the treatment and diagnosis of cancer, and they have recently been proven to be promising in cancer immunotherapy. Herein we concisely review the interesting immunomodulatory effects of dendrimers, in particular the recent advances in dendrimer‐facilitated cancer immunotherapy and cancer immunity visualization, and clarify the possible future perspectives for the design of dendrimer‐based cancer immunotheranostics.

Antifouling manganese oxide (Mn3O4) nanoparticles (NPs) were synthesized by solvothermal decomposition of tris(2,4-pentanedionato) manganese(III) in the presence of trisodium citrate, followed by surface modification with polyethylene glycol and l-cysteine. The as-prepared nanoparticles have a uniform size distribution, good colloidal stability and good cytocompatibility. The modification of l-cysteine rendered the particles with much longer blood circulation time (half-decay time of 28.4 h) than those without l-cysteine modification (18.5 h), and decreased macrophage cellular uptake. Thanks to desirable antifouling property and relatively high r1 relaxivity (3.66 mM–1 s–1), the l-cysteine-modified Mn3O4 NPs can be used for enhanced tumor magnetic resonance imaging applications.

Magnetic iron oxide nanoparticles (MIO NPs) bearing different appropriate surface modifications can be prepared using diverse physical and chemical methods. As an ideal macromolecule, dendrimers have attracted considerable attention because of their unique properties, including their three 3D architecture, monodispersity, highly branched macromolecular characteristics, and tunable terminal functionalities. These properties make dendrimers a powerful nanoplatform for the creation of functional organic and/or inorganic hybrid NPs, in particular dendrimer-based MIO NPs. Here, we report on recent advances in the preparation of dendrimer-based MIO NPs for different biomedical applications, such as magnetic resonance (MR) imaging, drug and gene delivery, and protein immobilization.

In this study, multiwalled carbon nanotubes (MWCNTs) were used to encapsulate a model anticancer drug, doxorubicin (Dox). Then, the drug-loaded MWCNTs (Dox/MWCNTs) with an optimized drug encapsulation percentage were mixed with poly(lactide-co-glycolide) (PLGA) polymer solution for subsequent electrospinning to form drug-loaded composite nanofibrous mats. The structure, morphology, and mechanical properties of the formed electrospun Dox/PLGA, MWCNTs/PLGA, and Dox/MWCNTs/PLGA composite nanofibrous mats were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and tensile testing. In vitro viability assay and SEM morphology observation of mouse fibroblast cells cultured onto the MWCNTs/PLGA fibrous scaffolds demonstrate that the developed MWCNTs/PLGA composite nanofibers are cytocompatible. The incorporation of Dox-loaded MWCNTs within the PLGA nanofibers is able to improve the mechanical durability and maintain the three-dimensional structure of the nanofibrous mats. More importantly, our results indicate that this double-container drug delivery system (both PLGA polymer and MWCNTs are drug carriers) is beneficial to avoid the burst release of the drug and able to release the antitumor drug Dox in a sustained manner for 42 days. The developed composite electrospun nanofibrous drug delivery system may be used as therapeutic scaffold materials for post-operative local chemotherapy.

Capture and detection of metastatic cancer cells are crucial for diagnosis and treatment of malignant neoplasm. Here, we report the use of folic acid (FA) modified electrospun poly(vinyl alcohol) (PVA)/polyethyleneimine (PEI) nanofibers for cancer cell capture applications. Electrospun PVA/PEI nanofibers crosslinked by glutaraldehyde vapor were modified with FA via a poly(ethylene glycol) (PEG) spacer, followed by acetylation of the fiber surface PEI amines. The formed FA-modified nanofibers were well characterized. The morphology of the electrospun PVA/PEI nanofibers is smooth and uniform despite the surface modification. In addition, the FA-modified nanofibers display good hemocompatibility as confirmed by hemolysis assay. Importantly, the developed FA-modified nanofibers are able to specifically capture cancer cells overexpressing FA receptors, which were validated by quantitative cell counting assay and qualitative confocal microscopy analysis. The developed FA-modified PVA/PEI nanofibers may be used for capturing circulating tumor cells for cancer diagnosis applications.

Development of various cost-effective contrast agents for targeted tumor computed tomography (CT) imaging still remains a great challenge. Herein, we present a facile approach to forming folic acid (FA)-targeted multifunctional gold nanoparticles (AuNPs) using cost-effective branched polyethylenimine (PEI) modified with polyethylene glycol (PEG) as a template for tumor CT imaging applications. In this work, PEI sequentially modified with PEG monomethyl ether, FA-linked PEG, and fluorescein isothiocyanate was used as a template to synthesize AuNPs, followed by transformation of the remaining PEI surface amines to acetamides. The formed FA-targeted PEI-entrapped AuNPs (FA-Au PENPs) were fully characterized. We show that the formed FA-Au PENPs with an Au core size of 2.1 nm are water soluble, colloidally stable, and non-cytotoxic in a given concentration range. Flow cytometry and confocal microscopy data reveal that the FA-Au PENPs are able to target cancer cells overexpressing FA receptors (FAR). Importantly, the developed FA-Au PENPs can be used as a nanoprobe for targeted CT imaging of FAR-expressing cancer cells in vitro and the xenografted tumor model in vivo. With the demonstrated biocompatibility by organ biodistribution and histological studies, the designed FA-Au PENPs may hold great promise to be used as a nanoprobe for CT imaging of different FAR-overexpressing tumors.

We report a facile approach to synthesizing hyaluronic acid (HA)-modified Fe3O4@Mn3O4 nanocomposites (NCs) for targeted T1/T2 dual-mode magnetic resonance (MR) imaging of cancer cells. In this work, branched polyethyleneimine (PEI)-coated Fe3O4@Mn3O4 NCs (Fe3O4@Mn3O4-PEI NCs) were first synthesized via a one-pot hydrothermal route, followed by modification of HA on the particle surface via PEI amines. The formed Fe3O4@Mn3O4-PEI-HA NCs were well characterized via different techniques. Our results manifest that the formed Fe3O4@Mn3O4-PEI-HA NCs possess good water dispersibility, colloidal stability, cytocompatibility in the studied concentration range, and targeting specificity to CD44 receptor-overexpressing cancer cells. Due to the coexistence of Fe3O4 and Mn3O4 in the particles, the Fe3O4@Mn3O4-PEI-HA NCs display relatively high r2 (143.26 mM−1 s−1) and r1 (2.15 mM−1 s−1) relaxivities, and can be used as an efficient nanoprobe for targeted T1/T2 dual-mode MR imaging of cancer cells in vitro. The developed Fe3O4@Mn3O4-PEI-HA NCs may hold great promise to be used as a nanoplatform for theranostics of different biological systems.

A multifunctional folic acid-targeted dendrimer-based nanoplatform was designed to have both Mn(II) and 99mTc loaded via chelation. The formed nanoplatform displays good stability, cytocompatibility and hemocompatibility in a given concentration range, and can be used for targeted dual-mode single-photon emission computed tomography/magnetic resonance imaging of tumors.

It is generally required to develop a nanocarrier system that is able to improve the water solubility of an anticancer drug and enable targeted delivery of the drug to cancer cells via a receptor-mediated endocytosis pathway. In this work, polyethyleneimine (PEI) was sequentially modified with dual functional polyethylene glycol (NH2–PEG–COOH), hyaluronic acid (HA), and fluorescein isothiocyanate (FI). The prepared PEI–FI–(PEG–HA) conjugate was then used as a nanoplatform to encapsulate the anticancer drug doxorubicin (DOX). We show that the formed PEI–FI–(PEG–HA) conjugate is able to encapsulate approximately 19 DOX molecules within each multifunctional PEI, and the formed PEI–FI–(PEG–HA)/DOX complexes can release DOX in a pH-dependent manner with a higher DOX release rate under an acidic pH condition than under a physiological pH condition. In addition, the PEI–FI–(PEG–HA)/DOX complexes are able to specifically target cancer cells overexpressing CD44 receptors as confirmed via flow cytometric analysis and confocal microscopic observation, and thus deliver DOX to the target cancer cells to inhibit their growth. The developed HA-targeted PEI may hold great promise to be used as an efficient nanoplatform for the targeted delivery of different anticancer drugs.

International audience; The advancement of biocompatible nanoplatforms with dual functionalities of diagnosis and therapeutics has been strongly demanded in biomedicine in recent years. In this work, we report the synthesis and characterization of polydopamine (pD)-coated gold nanostars (Au NSs) for computed tomography (CT) imaging and enhanced photothermal therapy (PTT) of tumors. Au NSs were firstly formed via a seed-mediated growth method and then stabilized with thiolated polyethyleneimine (PEI-SH), followed by deposition of pD on their surface. The formed pD-coated Au NSs (Au-PEI@pD NSs) were well characterized. We show that the Au-PEI@ pD NSs are able to convert the absorbed near-infrared laser light into heat, and have strong X-ray attenuation properties. Due to the co-existence of Au NSs and pD, the light to heat conversion efficiency of the NSs can be significantly enhanced. These very interesting properties allow them to be used as a powerful theranostic nanoplatform for efficient CT imaging and enhanced phtotothermal therapy of cancer cells in vitro and the xenografted tumor model in vivo. Due to their easy functionalization nature enabled by the coated pD shell, the developed pD-coated Au NSs may be used as a versatile nanoplatform for targeted CT imaging and PTT of different types of cancers.

Abundant reactive oxygen species and tumor necrosis factor-α (TNF-α) cytokine supply of M1-type macrophages boost rheumatoid arthritis (RA) pathological process. For efficient RA therapy, here a multifunctional nanoplatform is presented based on generation 5 (G5) poly(amidoamine) dendrimer-entrapped gold nanoparticles (Au DENPs) to achieve co-delivery of antioxidant alpha-tocopheryl succinate (α-TOS) and anti-inflammatory anti-TNF-α siRNA to macrophage cells. G5 dendrimers with amine termini are sequentially functionalized with 1,3-propane sultone (1,3-PS), α-TOS through a polyethylene glycol (PEG) spacer, and PEGylated folic acid (FA), and subsequently entrapped with Au NPs. The generated functional Au DENPs exhibit desired cytocompatibility, zwitterion-rendered antifouling property, and FA-mediated targeting specificity, enabling serum-enhanced siRNA delivery to M1-type macrophage cells. Meanwhile, the attached α-TOS affords enhanced oxidation resistance of macrophage cells. In vivo investigation shows that the treatment of a collagen-induced arthritis mouse model using α-TOS-modified Au DENPs/TNF-α siRNA polyplexes can achieve excellent combination therapy effect in inflammatory cytokines downregulation of RA lesion and bone erosions. The therapeutic efficacy is also supported by 3D micro-computed tomography analysis and TNF-α cytokine reduction of RA lesion joints in the mRNA, protein, and histology levels. The created multifunctional nanoplatform may be employed in antioxidative and anti-inflammatory combination therapy of RA.

International audience; Design of simple-component theranostic agents with enhanced tumor accumulation represents a novel strategy in the area of precision nanomedicine for effective tumor theranostics. Herein, we report an innovative theranostic strategy based on ultrasound-enhanced tumor accumulation of a theranostic agent of phosphorus dendrimer-copper(II) complexes (1G3-Cu). The employed 1G3-Cu complexes represent a drug-free nanotheranostic agent with a simple composition possessing an r1 relaxivity of 0.7024 mM−1 s−1 for T1-weighted magnetic resonance (MR) imaging and an IC50 of 1.24 μM to inhibit the growth of a pancreatic cancer cell line. We show that cancer cells can be inhibited by the 1G3-Cu complexes through the activation of the apoptotic process with the upregulation of Bax, P53 and PTEN, downregulation of Bcl-2, and decrease of intracellular ATP. With the assistance of ultrasound targeted microbubble destruction (UTMD) technology that can increase cell membrane permeability temporarily via sonoporation effect, the 1G3-Cu complexes enable enhanced tumor MR imaging and chemotherapy due to their improved tumor accumulation. With the proven minimal toxicity to normal tissues at imaging and therapeutic doses, the prepared 1G3-Cu complexes may be potentially employed for UTMD-enhanced theranostics of different types of cancer.

Imaging-guided interventional therapy is a promising means of minimally invasive and targeted drug delivery for patients with advanced pancreatic cancer. The effectiveness of the method depends on clear imaging and complete removal of cancer cells, especially peripheral infiltration and distant metastasis, to prevent recurrence. We synthesized hollow mesoporous silica-based nanoparticles, Gem-PFH-Au star-HMS-IGF1, with gemcitabine (Gem) and perfluorohexane (PFH) encapsulated internally, gold nanostars (Au NSs) and insulin-like growth factor-1 (IGF1) modified outwardly, to enhance multimode ultrasound (US)/computed tomography (CT)/photoacoustic (PA)/thermal imaging, guide photothermal therapy, and evaluate the effect in real time. We also prepared a type of thermosensitive gel that solidified at body temperature to facilitate the controlled release of Gem and achieve a single-administration interventional therapy. A patient-derived xenograft (PDX) mouse model was established in this study. The PDX was precisely ablated by photothermal therapy under the guidance of US/CT/PA imaging, and the residual pancreatic cancer cells were completely inhibited by Gem to prevent recurrence. This strategy ingeniously simulated the approach of surgical resection and postoperative chemotherapy in clinical procedures to treat malignancy and paves the way for interventional therapy.

Aim: To develop a multifunctional nanofibrous mat-embedded microfluidic chip system for specific capture and intact release of circulating tumor cells. Materials & methods: Electrospun polyethylenimine/polyvinyl alcohol nanofibers were functionalized with zwitterions to reduce the nonspecific adhesion of blood cells, followed by modification with arginine-glycine-aspartic acid peptide via an acid-sensitive benzoic imine bond. Results: The nanofiber-embedded microchip can be applied for capturing various types of cancer cells and circulating tumor cells with high efficiency and considerable purity. The captured cancer cells can be released from the nanofibrous substrates within 30 min. Conclusion: The developed multifunctional nanofiber-embedded microfluidic chip may have a great potential for clinical applications.

Development of multifunctional theranostic nanoplatforms with improved diagnostic sensitivity and therapeutic efficiency of tumors still remains a great challenge. A unique multifunctional theranostic nanoplatform based on generation 5 (G5) poly(amidoamine) dendrimer–stabilized gold nanoflowers (NFs) embedded with ultrasmall iron oxide (USIO) nanoparticles (NPs) for multimode T 1‐weighted magnetic resonance (MR)/computed tomography (CT)/photoacoustic (PA) imaging–guided combination photothermal therapy (PTT) and radiotherapy (RT) of tumors is reported here. G5 dendrimer–stabilized Au NPs and citric acid–stabilized USIO NPs are separately prepared, the two particles under a certain Fe/Au molar ratio are mixed to form complexes, the complexes are exposed to Au growth solution to form NFs via a seed–mediated manner, and the remaining dendrimer terminal amines are acetylated. The formed dendrimer‐stabilized Fe3O4/Au NFs (for short, Fe3O4/Au DSNFs) have a mean diameter of 99.8 nm, display good colloidal stability and cytocompatibility, and exhibit a near‐infrared absorption feature. The unique structure and composition of the Fe3O4/Au DSNFs endows them with a high r 1 relaxivity (3.22 mM−1 s−1) and photothermal conversion efficiency (82.7%), affording their uses as a theranostic nanoplatform for multimode MR/CT/PA imaging and combination PTT/RT of tumors with improved therapeutic efficacy, which is important for translational nanomedicine applications.

We report the polyethylenimine (PEI)-mediated immobilization of palladium nanoparticles (Pd NPs) onto filter paper for catalytic applications. In this work, filter paper was first assembled with PEI via electrostatic interaction, and the PEI-assembled filter paper was then complexed with PdCl42− ions, followed by sodium borohydride reduction to generate Pd NP-immobilized filter paper. Transmission electron microscopy reveals that Pd NPs have a diameter of 3 nm and are capable of being immobilized onto the filter paper. The Pd NP-immobilized filter paper exhibits remarkable catalytic activity and is reusable in the reductive transformation of Cr(VI) to Cr(III) and 4-nitrophenol to 4-aminophenol. The strategy used to develop Pd NP-immobilized filter paper could be adopted to generate other metal NP-immobilized filter papers for other applications such as sensing materials, energy, environmental remediation, and biomedical sciences.

Developing an effective computed tomography (CT) contrast agent is still a challenging task for precise diagnosis of hepatic carcinoma (HCC). Here, we present the use of acetylated polyethylenimine (PEI)-entrapped gold nanoparticles (Ac-PE-AuNPs) without antifouling modification for negative CT imaging of HCC. PEI was first linked to fluorescein isothiocyanate (FI) and then utilized as a vehicle for the entrapment of AuNPs. The particles were then acetylated to reduce its positive surface potential. The designed Ac-PE-AuNPs were characterized by various techniques. We find that the Ac-PE-AuNPs with a uniform size distribution (mean diameter = 2.3 nm) are colloidally stable and possess low toxicity in the studied range of concentration. Owing to the fact that the particles without additional antifouling modification were mainly gathered in liver, the Ac-PE-AuNPs could greatly improve the CT contrast enhancement of normal liver, whereas poor CT contrast enhancement appeared in liver necrosis region caused by HCC. As a result, HCC could be easily and precisely diagnosed. The designed Ac-PE-AuNPs were demonstrated to have biocompatibility through in vivo biodistribution and histological studies, hence holding an enormous potential to be adopted as an effective negative CT contrast agent for diagnosis of hepatoma carcinoma.

We report the construction and characterization of 99mTc-labeled arginine-glycine-aspartic acid (RGD)–polyethylenimine (PEI) conjugates with entrapped gold nanoparticles in the cavities (RGD–99mTc–Au PENPs) for dual-mode single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of an orthotopic hepatic carcinoma model. In this study, PEI was successively decorated with diethylenetriaminepentaacetic acid, poly(ethylene glycol) (PEG), and PEGylated RGD segments, and was utilized as an effective nanoplatform to entrap Au NPs and to be labeled with 99mTc. We showed that the designed RGD–99mTc–Au PENPs displayed desirable colloidal stability and radiostability, and cytocompatibility in the investigated concentration range, and could be specifically uptaken by αvβ3 integrin-overexpressing liver cancer cells in vitro. In vivo CT and SPECT imaging results indicated that the particles were able to be accumulated within an orthotopic hepatic carcinoma and displayed both CT and SPECT contra...

Novel theranostic nanocarriers exhibit a desirable potential to treat diseases based on their ability to achieve targeted therapy while allowing for real-time imaging of the disease site. Development of such theranostic platforms is still quite challenging. Herein, we present the construction of multifunctional dendrimer-based theranostic nanosystem to achieve cancer cell chemotherapy and computed tomography (CT) imaging with targeting specificity. Doxorubicin (DOX), a model anticancer drug, was first covalently linked onto the partially acetylated poly(amidoamine) dendrimers of generation 5 (G5) prefunctionalized with folic acid (FA) through acid-sensitive cis-aconityl linkage to form G5·NHAc-FA-DOX conjugates, which were then entrapped with gold (Au) nanoparticles (NPs) to create dendrimer-entrapped Au NPs (Au DENPs). We demonstrate that the prepared DOX-Au DENPs possess an Au core size of 2.8 nm, have 9.0 DOX moieties conjugated onto each dendrimer, and are colloid stable under different conditions. The formed DOX-Au DENPs exhibit a pH-responsive release profile of DOX because of the cis-aconityl linkage, having a faster DOX release rate under a slightly acidic pH condition than under a physiological pH. Importantly, because of the coexistence of targeting ligand FA and Au core NPs as a CT imaging agent, the multifunctional DOX-loaded Au DENPs afford specific chemotherapy and CT imaging of FA receptor-overexpressing cancer cells. The constructed DOX-conjugated Au DENPs hold a promising potential to be utilized for simultaneous chemotherapy and CT imaging of various types of cancer cells.

International audience; The aim of this original review is to highlight and analyze the most recent progress and challenges in the synthesis and surface modifications of superparamagnetic iron oxide (Fe3O4) nanoparticles (NPs) for multimodal imaging and therapy applications, which represent important fields in medicine in general and cancer in particular. Thus, the oncology domain is rapidly moving to a more personalized medicine including precision imaging and theranostic approaches. Novel biocompatible Fe3O4 nanoparticulate systems have been designed for enhanced and targeted cellular uptake by surface layer coating modifications, to have improved r2 relaxivity for sensitive magnetic resonance (MR) imaging applications, to have the ability to be used for dual mode imaging, and to be used for imaging-guided cancer therapy. In this review, we analyzed in depth the new strategies for generating biocompatible multifunctional Fe3O4 nanoplatforms for both the diagnosis and therapy of cancer.

The facile hydrothermal synthesis of polyethyleneimine (PEI)-coated iron oxide (Fe3O4) nanoparticles (NPs) doped with Gd(OH)3 (Fe3O4-Gd(OH)3-PEI NPs) for dual mode T1- and T2-weighted magnetic resonance (MR) imaging applications is reported. In this approach, Fe3O4-Gd(OH)3-PEI NPs are synthesized via a hydrothermal method in the presence of branched PEI and Gd(III) ions. The PEI coating onto the particle surfaces enables further modification of poly(ethylene glycol) (PEG) in order to render the particles with good water dispersibility and improved biocompatibility. The formed Fe3O4-Gd(OH)3-PEI-PEG NPs have a Gd/Fe molar ratio of 0.25:1 and a mean particle size of 14.4 nm and display a relatively high r2 (151.37 × 10−3m−1 s−1) and r1 (5.63 × 10−3m−1 s−1) relaxivity, affording their uses as a unique contrast agent for T1- and T2-weighted MR imaging of rat livers after mesenteric vein injection of the particles and the mouse liver after intravenous injection of the particles, respectively. The developed Fe3O4-Gd(OH)3-PEI-PEG NPs may hold great promise to be used as a contrast agent for dual mode T1- and T2-weighted self-confirmation MR imaging of different biological systems.

A unique dendrimer-assisted approach is reported to create Fe3O4/Au nanocomposite particles (NCPs) for targeted dual mode computed tomography/magnetic resonance (CT/MR) imaging of tumors. In this approach, preformed Fe3O4 nanoparticles (NPs) are assembled with multilayers of poly(γ-glutamic acid) (PGA)/poly(L-lysine)/PGA/folic acid (FA)-modified dendrimer-entrapped gold nanoparticles via a layer-by-layer self-assembly technique. The interlayers are crosslinked via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide chemistry, the assembled Au core NPs are then used as seed particles for subsequent seed-mediated growth of Au shells via iterative Au salt reduction process, and subsequent acetylation of the remaining amines of dendrimers leads to the formation of Fe3O4/Au(n.)Ac-FA NCPs with a tunable molar ratio of Au/Fe3O4. It is shown that the Fe3O4/Au(n.)Ac-FA NCPs at an optimized Au/Fe3O4 molar ratio of 2.02 display a relatively high R2 relaxivity (92.67 × 10(-3) M(-1) s(-1)) and good X-ray attenuation property, and are cytocompatible and hemocompatible in the given concentration range. Importantly, with the FA-mediated targeting, the Fe3O4/Au(n.)Ac-FA NCPs are able to be specifically uptaken by cancer cells overexpressing FA receptors, and be used as an efficient nanoprobe for targeted dual mode CT/MR imaging of a xenografted tumor model. With the versatile dendrimer chemistry, the developed Fe3O4/Au NCPs may be differently functionalized, thereby providing a unique platform for diagnosis and therapy of different biological systems.

This article reports a new approach for the synthesis of ultrasmall iron oxide nanoparticles (NPs) conjugated with Arg-Gly-Asp (RGD)-modified dendrimers (G5.NHAc-RGD-Fe3O4 NPs) as a platform for targeted magnetic resonance (MR) imaging of C6 glioma cells. Ultrasmall Fe3O4 NPs synthesized via a solvothermal route were conjugated with RGD peptide-modified generation-5 poly(amidoamine) dendrimers (G5.NH2-RGD). The final G5.NHAc-RGD-Fe3O4 NPs were formed following the acetylation of the remaining dendrimer terminal amines. The as-prepared multifunctional Fe3O4 NPs were characterized using various techniques. The results of a cell viability assay, cell morphological observation, and hemolysis assay indicated that the G5.NHAc-RGD-Fe3O4 NPs exhibit excellent cytocompatibility and hemocompatibility over the studied concentration range. In addition, RGD conjugated onto the Fe3O4 NPs allows for the efficient targeting of the particles to C6 cells that overexpress αvβ3 receptors, which was confirmed via in vitro cell MR imaging and cellular uptake. Finally, the G5.NHAc-RGD-Fe3O4 NPs were used in the targeted MR imaging of C6 glioma cells in mice. The results obtained from the current study indicate that the developed G5.NHAc-RGD-Fe3O4 NPs offer significant potential for use as contrast agents in the targeted MR imaging of different types of tumors.

We report a facile approach to immobilizing lactobionic acid (LA) onto electrospun polyvinyl alcohol (PVA)/polyethyleneimine (PEI) nanofibers through a polyethylene glycol (PEG) spacer for capturing hepatocellular carcinoma cells. In this work, electrospun PVA/PEI nanofibers were crosslinked using glutaraldehyde vapor, covalently conjugated with PEGylated LA via an N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) coupling reaction, followed by acetylation of the remaining PEI amines on the fiber surface. The formed LA-functionalized nanofibers were characterized via scanning electron microscopy and attenuated total reflectance-Fourier transform infrared spectroscopy. We show that the fiber morphology does not significantly change after fiber surface modification. The functionalized nanofibers display good hemocompatibility and superior capability to capture asialoglycoprotein receptor (ASGPR)-overexpressing hepatocellular carcinoma cells in vitro via a ligand–receptor interaction. The developed LA-modified PVA/PEI nanofibers may be applied to capture circulating tumor cells for cancer diagnosis applications.

A facile approach to assembling polyethyleneimine (PEI)-entrapped gold nanoparticles (Au PENPs) onto filter paper is reported. In this work, Au PENPs with an Au core size of 3.2 ± 0.8 nm were formed using PEI as a template, followed by adsorption onto filter paper. The formed Au PENP-containing filter paper was characterized by various techniques. We show that the Au PENPs are able to be adsorbed onto filter paper likely due to the microfibrous structure of the paper and the electrostatic interaction between the positively charged Au PENPs and the negatively charged filter paper. Furthermore, we demonstrate that the Au PENP-assembled filter paper displays an excellent catalytic activity and reusability to converting 4-nitrophenol to 4-aminophenol. Such a development of Au PENP-assembled filter paper may be applicable for the immobilization of other metal NPs onto filter paper for various applications in catalysis, sensing, and biomedical sciences.

Development of cost-effective nanoscale contrast agents for targeted tumor computed tomography (CT) imaging remains a great challenge. Here, we report the synthesis of dendrimer-entrapped AuNPs (Au DENPs) using generation 2 poly(amidoamine) dendrimers pre-modified with fluorescein isothiocyanate via a thiourea linkage and lactobionic acid (LA) via a polyethylene glycol spacer as templates. The formed Au DENPs were characterized via different techniques and were used as a nanoprobe for targeted CT imaging of hepatocellular carcinoma (HCC). We show that the LA-modified Au DENPs with a mean Au core size of 1.8 nm are water-dispersible, colloidally stable under different temperatures (4-50 °C) and pH (5-8) conditions, and cytocompatible in the studied concentration range. Flow cytometry results reveal that the LA-Au DENPs are able to specifically target HepG2 cells (a human HCC cell line) overexpressing asialoglycoprotein receptors via a receptor-mediated targeting pathway. Importantly, the developed LA-Au DENPs can be used as a nanoprobe for targeted CT imaging of HepG2 cells in vitro and the xenografted tumor model in vivo. With the demonstrated organ compatibility, the developed LA-Au DENPs using low-generation dendrimers as templates can be a good candidate to be used as a highly efficient and cost-effective nanoprobe for targeted CT imaging of HCC.

We report a facile approach to form iron oxide nanoparticle (NP)-loaded γ-polyglutamic acid (γ-PGA) nanogels (NGs) for MR imaging of tumors. In this study, γ-PGA with carboxyl groups activated by 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) in aqueous solution was firstly emulsified, followed by in situ chemical crosslinking with polyethyleneimine (PEI)-coated iron oxide NPs (PEI–Fe3O4 NPs) with a core size of 8.9 ± 2.1 nm synthesized via a mild reduction route. The formed γ-PGA NGs containing iron oxide NPs (γ-PGA/PEI–Fe3O4 NGs) with a size of 152.3 ± 13.1 nm are water-dispersible, colloidally stable, noncytotoxic in a given concentration range, and display a r2 relaxivity of 171.1 mM−1 s−1. Likewise, the hybrid NGs can be taken up by cancer cells with the uptake of Fe significantly higher than single Fe3O4 NPs. These properties render the formed γ-PGA/PEI–Fe3O4 NGs with an ability to be used as an effective contrast agent for MR imaging of cancer cells in vitro and the xenografted tumor model in vivo via the passive enhanced permeability and retention effect after intravenous injection. The developed γ-PGA/PEI–Fe3O4 hybrid NGs may hold great promise to be used as a novel contrast agent for MR imaging or other theranostic applications.

A facile co-precipitation approach for synthesizing hyaluronic acid (HA)-modified Fe3O4/Au composite nanoparticles (CNPs) for targeted dual mode tumor magnetic resonance (MR) and computed tomography (CT) imaging is reported. In this work, polyethyleneimine (PEI) was employed as a stabilizer to form gold NPs (PEI–Au NPs). In the presence of the PEI–Au NPs, controlled co-precipitation of Fe(II) and Fe(III) salts was performed, leading to the formation of the Fe3O4/Au–PEI CNPs, which were further modified with hyaluronic acid (HA). We show that the formed Fe3O4/Au–PEI–HA CNPs are colloidally stable, hemocompatible and cytocompatible in a given concentration range, and have a high affinity to target CD44 receptor-overexpressing cancer cells. Due to the presence of Fe3O4 and Au components, the formed Fe3O4/Au–PEI–HA CNPs display a high r2 relaxivity (264.16 mM−1 s−1) and good X-ray attenuation property, rendering them with an ability to be used as a nanoprobe for targeted dual mode MR/CT imaging of CD44 receptor-overexpressing cancer cells in vitro and a xenografted tumor model in vivo. The Fe3O4/Au–PEI–HA CNPs developed via this facile approach may hold great promise to be used as a unique platform for precision imaging of CD44 receptor-overexpressing tumors.