Self‐Assembled Nanoparticles with Dual Effects of Passive Tumor Targeting and Cancer‐Selective Anticancer Effects

Nanoparticular drug delivery systems may help to overcome the limitations of conventional chemotherapy. They have been reported to improve the specificity of distribution, the bioavailability, and the solubility of drugs, as well as the duration of drug efficacy, and helping to overcome multidrug resistance. Although various polymeric nanoparticles have been developed for delivery of anticancer agents, most nanoparticles still focus on solubilizing drugs, improving targeting ability, and reducing side effects. In particular, targeting to the tumor is typically improved through passive or active targeting. Despite great achievements in both strategies, yet to be resolved are issues of toxicity in normal cells and enhancement of tumor‐specificity. A new approach combining the dual strategies of passive tumor targeting and cancer‐selective efficacy is proposed. Recombinant human gelatin conjugated with lipoic acid (rHG‐LA) developed in this study forms nanoparticles spontaneously in aqueous solution and encapsulates alpha‐tocopheryl succinate (α‐TOS), a well‐known cancer‐selective apoptosis‐inducing agent, within a hydrophobic core during the self‐assembly. This study describes the promising applicability of α‐TOS‐loaded rHG‐LA nanoparticles with passive targeting ability and cancer‐specificity.     

Targeted Tumor Hypoxia Dual‐Mode CT/MR Imaging and Enhanced Radiation Therapy Using Dendrimer‐Based Nanosensitizers

The efficacy of radiation therapy (RT) is often limited by the poor response of hypoxia inside most solid tumors. The development of a theranostic nanoplatform for precision‐imaging‐guided sensitized RT for tumor hypoxia is still challenging. Herein, the creation of hypoxia‐targeted dendrimer‐entrapped gold nanoparticles complexed with gadolinium(III) (Gd‐Au DENPs‐Nit) for dual‐mode CT/MR imaging and sensitized RT of hypoxic tumors is reported. In this work, generation 5 poly(amidoamine) dendrimers are partially conjugated with Gd(III) chelator, entrapped with Au nanoparticles, and conjugated with hypoxia‐targeting agent nitroimidazole via a polyethylene glycol linker, and ending with chelation of Gd(III) and conversion of their leftover amine termini to acetamides. The designed dendrimer‐based nanohybrids with 3.2 nm Au cores exhibit an excellent X‐ray attenuation effect, acceptable r₁ relaxivity (1.32 mM^?1 s^?1), and enhanced cellular uptake in hypoxic cancer cells, affording efficient dual‐mode CT/MR imaging of tumor hypoxia. Under X‐ray irradiation, the Gd‐Au DENPs‐Nit nanohybrids can produce reactive oxygen species, promote DNA damage, and prevent DNA repair, facilitating sensitized RT of hypoxic cancer cells in vitro and tumor hypoxia in vivo. The developed hypoxia‐targeted dendrimer‐based nanohybrids may be employed as both contrast agents and nanosensitizers for precision tumor hypoxia imaging and sensitized tumor RT.     

A Smart Nanoassembly for Multistage Targeted Drug Delivery and Magnetic Resonance Imaging

Efficient delivery of DNA‐toxin anticancer drugs into nucleus of targeted tumor cells while simultaneously minimizing the side effects to normal tissue is a major challenge for cancer therapy. Herein, a multistage continuous targeting strategy based on magnetic mesoporous silica nanoparticles to overcome the challenge is demonstrated. At the initial‐stage, the magnetic nanoparticle is capable of efficiently accumulating in tumor tissue guided by magnet. Following by the magnetic targeting, the targeting ligand gets it right into the cancer cell by receptor‐mediated endocytosis. Accompanied by endocytosis into the lysosomes, the nanoparticle reverses its surface charge from negative to positive which leads to the separation of charge‐conversional polymer from the nanoparticle to re‐expose the nuclear‐targeting TAT peptide. Finally, TAT peptide facilitates the carriers to enter nucleus and the DNA‐toxin camptothecin can inhibit topoisomerase I to induce cell apoptosis. Furthermore, the nano‐drug delivery system can be simultaneously used as predominant contrast agents for magnetic resonance imaging. This proof of concept might open the door to a new generation of carrier materials in the fields of targeted drug transport platform for cancer theranostics.     

Actively Targeted Deep Tissue Imaging and Photothermal‐Chemo Therapy of Breast Cancer by Antibody‐Functionalized Drug‐Loaded X‐Ray‐Responsive Bismuth Sulfide@Mesoporous Silica Core–Shell Nanoparticles

A theranostic platform combining synergistic therapy and real‐time imaging attracts enormous attention but still faces great challenges, such as tedious modifications and lack of efficient accumulation in tumor. Here, a novel type of theranostic agent, bismuth sulfide@mesoporous silica (Bi₂S₃@mPS) core‐shell nanoparticles (NPs), for targeted image‐guided therapy of human epidermal growth factor receptor‐2 (HER‐2) positive breast cancer is developed. To generate such NPs, polyvinylpyrrolidone decorated rod‐like Bi₂S₃ NPs are chemically encapsulated with a mesoporous silica (mPS) layer and loaded with an anticancer drug, doxorubicin. The resultant NPs are then chemically conjugated with trastuzumab (Tam, a monoclonal antibody targeting HER‐2 overexpressed breast cancer cells) to form Tam‐Bi₂S₃@mPS NPs. By in vitro and in vivo studies, it is demonstrated that the Tam‐Bi₂S₃@mPS bear multiple desired features for cancer theranostics, including good biocompatibility and drug loading ability as well as precise and active tumor targeting and accumulation (with a bismuth content in tumor being ≈16 times that of nontargeted group). They can simultaneously serve both as an excellent contrast enhancement probe (due to the presence of strong X‐ray‐attenuating bismuth element) for computed tomography deep tissue tumor imaging and as a therapeutic agent to destruct tumors and prevent metastasis by synergistic photothermal‐chemo therapy.     

Fabricating Aptamer‐Conjugated PEGylated‐MoS2/Cu1.8S Theranostic Nanoplatform for Multiplexed Imaging Diagnosis and Chemo‐Photothermal Therapy of Cancer

Fabricating theranostic nanoparticles combining multimode disease diagnosis and therapeutic has become an emerging approach for personal nanomedicine. However, the diagnostic capability, biocompatibility, and therapeutic efficiency of theranostic nanoplatforms limit their clinic widespread applications. Targeting to the theme of accurate diagnosis and effective therapy of cancer cells, a multifunctional nanoplatform of aptamer and polyethylene glycol (PEG) conjugated MoS₂ nanosheets decorated with Cu_1.8S nanoparticles (ATPMC) is developed. The ATPMC nanoplatform accomplishes photoluminescence imaging, photoacoustic imaging, and photothermal imaging for in vitro and in vivo tumor cells imaging diagnosis. Meanwhile, the ATPMC nanoplatform facilitates selective delivery of gene probe to detect intracellular microRNA aberrantly expressed in cancer cells and anticancer drug doxorubicin (DOX) for chemotherapy. Moreover, the synergistic interaction of MoS₂ and Cu_1.8S renders the ATPMC nanoplatform with superb photothermal conversion efficiency. The ATPMC nanoplatform loaded with DOX displays near‐infrared laser‐induced programmed chemotherapy and advanced photothermal therapy, and the targeted chemo‐photothermal therapy presents excellent antitumor efficiency.     

Cancer‐Targeted Monodisperse Mesoporous Silica Nanoparticles as Carrier of Ruthenium Polypyridyl Complexes to Enhance Theranostic Effects

Mesoporous silica nanoparticles (MSNs) have been well‐demonstrated as excellent carriers for anticancer drug delivery. Presented here is a cancer‐targeted MSNs drug delivery system that allows the direct fluorescence monitoring of the cellular uptake and localization of theranostic agents in cancer cells. Specifically, the anticancer action mechanisms of RGD peptide‐functionalized MSNs carrying ruthenium polypyridyl complexes (RuPOP@MSNs) are elucidated in detail. RGD peptide surface decoration significantly enhances the cellular uptake of the nanoparticles through receptor‐mediated endocytosis, and increases the selectivity between cancer and normal cells. RuPOP@MSNs exhibits unprecedented enhanced cytotoxicity toward cancer cells overexpressing integrin receptor, which is significantly higher than that of free RuPOP, through induction of apoptosis. The important contribution of extrinsic pathway to cell apoptosis is confirmed by increase in expression levels of death receptors, activation of caspase‐8 and truncation of Bid. The internalized nanoparticles release free RuPOP into the cytoplasm, where they modulate the phosphorylation of p53, AKT, and MAPKs pathways to promote cell apoptosis. Moreover, the strong autofluorescence of RuPOP permits the direct monitoring of drug delivery, and extends the power of theranostics to subcellular level. Taken together, this study provides an effective strategy for the design and development of cancer‐targeted theranostic agents.     

Targeted Nanoparticle‐Mediated Gene Therapy Mimics Oncolytic Virus for Effective Melanoma Treatment

Oncolytic virus has potential applications in cancer therapy. However, its clinical application is restricted by the virus‐associated biosafety issues. Here, inspired by the key role of vesicular stomatitis virus matrix protein (VSVMP) in the oncolytic vesicular stomatitis virus (VSV) induced apoptosis, a targeted nanoparticle‐delivered neutral VSVMP gene formulation is designed to act like the VSV for cancer therapy. This VSVMP formulation consists of a CRGDKGPDC peptide modified hybrid monomethoxy poly (ethylene glycol)‐poly(d ,l ‐lactide) nanoparticles complexed with VSVMP plasmid, having good blood compatibility and tumor targeting ability. The transfection efficiency is as high as that of VSV. After intravenous administration, the VSVMP formulation can efficiently target the tumor, significantly inhibit the melanoma growth and metastasis, prolong the survival time of tumor‐bearing mice, and does not cause obvious systemic toxicity. The anticancer mechanisms involve apoptosis induction, angiogenesis inhibition and some virus‐associated signal pathways activation. This work demonstrates a VSV‐inspired nonviral gene therapy that has promising clinical applications in melanoma treatment.     

Photosynthetic Biohybrid Nanoswimmers System to Alleviate Tumor Hypoxia for FL/PA/MR Imaging‐Guided Enhanced Radio‐Photodynamic Synergetic Therapy

Biohybrid microswimmers have recently shown to be able to actively perform in targeted delivery and in vitro biomedical applications. However, more envisioned functionalities of the microswimmers aimed at in vivo treatments are still challenging. A photosynthetic biohybrid nanoswimmers system (PBNs), magnetic engineered bacteria‐Spirulina platensis, is utilized for tumor‐targeted imaging and therapy. The engineered PBNs is fabricated by superparamagnetic magnetite (Fe₃O₄ NPs) via a dip‐coating process, enabling its tumor targeting ability and magnetic resonance imaging property after intravenous injection. It is found that the PBNs can be used as oxygenerator for in situ O₂ generations in hypoxic solid tumors through photosynthesis, modulating the tumor microenvironment (TME), thus improving the effectiveness of radiotherapy (RT). Furthermore, the innate chlorophyll released from the RT‐treated PBNs, as a photosensitizer, can produce cytotoxic reactive oxygen species under laser irradiation to achieve photodynamic therapy. Excellent tumor inhibition can be realized by the combined multimodal therapies. The PBNs also possesses capacities of chlorophyll‐based fluorescence and photoacoustic imaging, which can monitor the tumor therapy and tumor TME environment. These intriguing properties of the PBNs provide a promising microrobotic platform for TME hypoxic modulation and cancer theranostic applications.     

Construction of a Biomimetic Magnetosome and Its Application as a SiRNA Carrier for High‐Performance Anticancer Therapy

Precisely delivering siRNA to its target site in cancer cells is a high‐demanding but challenging task. Herein, a biomimetic magnetosome is developed using magnetic nanocluster (MNC) as the core and Arg–Gly–Asp (RGD) decorated macrophage membrane as the cloak, which is achieved via a combination of MNC synthesis, azide‐membrane engineering, electrical assembly, and click chemistry. Such a feature‐packed magnetosome enables us to gain the success of high‐performance siRNA delivery through superior stealth effect, magnetic resonance imaging, magnetic accumulation, RGD targeting, and favorable cytoplasm trafficking. As a result, target gene expression can be significantly suppressed and tumor growth is effectively inhibited, while the systemic toxicity is not notable. These results together vote the biomimetic magnetosome as a promising siRNA delivery system for anticancer therapy.     

Specific Near‐IR Absorption Imaging of Glioblastomas Using Integrin‐Targeting Gold Nanorods

Molecular imaging using nanoprobes with high resolution and low toxicity is essential in early cancer detection. Here we introduce a new class of smart imaging probes employing PEGylated gold nanorods (GNRs) conjugated to cRGD for specific optical imaging of α_vβ₃ integrins from glioblastoma. GNRs exhibiting an optical resonance peak in the near‐infrared (NIR) region were synthesized using the seed‐mediated growth method. CTAB (cetyl trimethylammonium bromide) bilayer on the GNRs was replaced with a biocompatible stabilizer, heterobifunctional polyethyleneglycol (COOH‐PEG‐SH). Further, the carboxylated GNRs (PGNRs; PEG‐coated GNRs) were functionalized with cRGD using EDC‐NHS chemistry to formulate cRGD‐conjugated GNRs (cRGD‐PGNRs) for α_vβ₃ integrins. In order to assess the potential of the cRGD‐PGNRs as a targeted imaging probe, we investigated their optical properties, biocompatibility, colloidal stability and in vitro/in vivo binding affinities for cancer cells. Consequently, cRGD‐PGNRs demonstrated excellent tumor targeting ability with no cytotoxicity, as well as sufficient cellular uptake due to stable and prolonged blood circulation of cRGD‐PGNRs.     

Gel–Liposome‐Mediated Co‐Delivery of Anticancer Membrane‐Associated Proteins and Small‐Molecule Drugs for Enhanced Therapeutic Efficacy

A programmed drug‐delivery system that can transport different anticancer therapeutics to their distinct targets holds vast promise for cancer treatment. Herein, a core–shell‐based “nanodepot” consisting of a liposomal core and a crosslinked‐gel shell (designated Gelipo) is developed for the sequential and site‐specific delivery (SSSD) of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and doxorubicin (Dox). As a small‐molecule drug intercalating the nuclear DNA, Dox is loaded in the aqueous core of the liposome, while TRAIL, acting on the death receptor (DR) on the plasma membrane, is encapsulated in the outer shell made of crosslinked hyaluronic acid (HA). The degradation of the HA shell by HAase that is concentrated in the tumor environment results in the rapid extracellular release of TRAIL and subsequent internalization of the liposomes. The parallel activity of TRAIL and Dox show synergistic anticancer efficacy. The half‐maximal inhibitory concentration (IC₅₀) of TRAIL and Dox co‐loaded Gelipo (TRAIL/Dox‐Gelipo) toward human breast cancer (MDA‐MB‐231) cells is 83 ng mL^–1 (Dox concentration), which presents a 5.9‐fold increase in the cytotoxicity compared to 569 ng mL^–1 of Dox‐loaded Gelipo (Dox‐Gelipo). Moreover, with the programmed choreography, Gelipo significantly improves the inhibition of the tumor growth in the MDA‐MB‐231 xenograft tumor animal model.     

Antitumor Platelet‐Mimicking Magnetic Nanoparticles

Nanoparticles possess the potential to revolutionize cancer diagnosis and therapy. The ideal theranostic nanoplatform should own long system circulation and active cancer targeting. Additionally, it should be nontoxic and invisible to the immune system. Here, the authors fabricate an all‐in‐one nanoplatform possessed with these properties for personalized cancer theranostics. Platelet‐derived vesicles (PLT‐vesicles) along with their membrane proteins are collected from mice blood and then coated onto Fe₃O₄ magnetic nanoparticles (MNs). The resulting core–shell PLT‐MNs, which inherit the long circulation and cancer targeting capabilities from the PLT membrane shell and the magnetic and optical absorption properties from the MN core, are finally injected back into the donor mice for enhanced tumor magnetic resonance imaging (MRI) and photothermal therapy (PTT). Meanwhile, it is found that the PTT treatment impels PLT‐MNs targeting to the PTT sites (i.e., tumor sites), and exactly, in turn, the enhanced targeting of PLT‐MNs to tumor sites can improve the PTT effects. In addition, since the PLT membrane coating is obtained from the mice and finally injected into the same mice, PLT‐MNs exhibit stellar immune compatibility. The work presented here provides a new angle on the design of biomimetic nanoparticles for personalized diagnosis and therapy of various diseases.     

Metal–Organic Framework Assisted and Tumor Microenvironment Modulated Synergistic Image‐Guided Photo‐Chemo Therapy

The complex tumor microenvironment (TME) and nonspecific drug targeting limit the clinical efficacy of photodynamic therapy in combination with chemotherapy. Herein, a metal–organic framework (MOF) assisted strategy is reported that modulates TME by reducing tumor hypoxia and intracellular glutathione (GSH) and offers targeted delivery and controlled release of the trapped chemodrug. Platinum(IV)‐diazido complex (Pt(IV)) is loaded inside a Cu(II) carboxylate‐based MOF, MOF‐199, and an aggregation‐induced‐emission photosensitizer, TBD, is conjugated to polyethylene glycol for encapsulating Pt(IV)‐loaded MOF‐199. Once the fabricated TBD‐Pt(IV)@MOF‐199 nanoparticles are internalized by cancer cells, MOF‐199 consumes intracellular GSH and decomposes to fragments to release Pt(IV). Upon light irradiation, the released Pt(IV) generates O₂ that relieves hypoxia and produces Pt(II)‐based chemodrug inside cancer cells. Concomitantly, efficient reactive oxygen species generation and bright emission are afforded by TBD, resulting in synergistic image‐guided photo‐chemo therapy with enhanced efficacies and mitigated side effects.     

Treatment of Malignant Brain Tumor by Tumor‐Triggered Programmed Wormlike Micelles with Precise Targeting and Deep Penetration

The efficient and specific drug delivery to brain tumor is a crucial challenge for successful systemic chemotherapy. To overcome these limitations, here a tumor‐triggered programmed wormlike micelle is reported with precise targeting and deep penetration to treat malignant gliomas, which is composed of pH‐responsive mPEG‐b‐PDPA copolymer and bioreducible cyclic RGD peptide targeted cytotoxic emtansine (DM1) conjugates (RGD‐DM1). The RGD‐DM1 loaded nanoscaled wormlike micelles (RNW) exhibit nanometer‐sized wormlike assemblies with the transverse diameter of 21.3±1.8 nm and length within 60–600 nm, and the RGD targeting peptide in RNW is 4.2% in weight. RNW can be dissociated at intracellular acidic environments to release RGD‐DM1, and be further degraded into DM1 by cleavage of disulfide bonds in the reductive milieu. In particular, by exploiting the unique wormlike structure and the RGD targeting peptide modification, RNW can be endowed with obviously enhanced drug delivery to brain, precise targeting to brain tumor, deep penetration into tumor mass, and efficient internalization into glioma cells in a programmed manner, thereby surprisingly leading to an 88.9% inhibition on tumor progression in an orthotopic brain tumor model. Therefore, the properly designed RNW can provide a promising delivery platform for systemic chemotherapy of brain tumor.     

A New Single 808 nm NIR Light‐Induced Imaging‐Guided Multifunctional Cancer Therapy Platform

The NIR light‐induced imaging‐guided cancer therapy is a promising route in the targeting cancer therapy field. However, up to now, the existing single‐modality light‐induced imaging effects are not enough to meet the higher diagnosis requirement. Thus, the multifunctional cancer therapy platform with multimode light‐induced imaging effects is highly desirable. In this work, captopril stabilized‐Au nanoclusters Au₂₅(Capt)₁₈?(Au₂₅) are assembled into the mesoporous silica shell coating outside of Nd³⁺‐sensitized upconversion nanoparticles (UCNPs) for the first time. The newly formed Au₂₅ shell exhibits considerable photothermal effects, bringing about the photothermal imaging and photoacoustic imaging properties, which couple with the upconversion luminescence imaging. More importantly, the three light‐induced imaging effects can be simultaneously achieved by exciting with a single NIR light (808 nm), which is also the triggering factor for the photothermal and photodynamic cancer therapy. Besides, the nanoparticles can also present the magnetic resonance and computer tomography imaging effects due to the Gd³⁺ and Yb³⁺ ions in the UCNPs. Furthermore, due to the photodynamic and the photothermal effects, the nanoparticles possess efficient in vivo tumor growth inhibition under the single irradiation of 808 nm light. The multifunctional cancer therapy platform with multimode imaging effects realizes a true sense of light‐induced imaging‐guided cancer therapy.     

Hyperbranched Polyglycerol‐Grafted Superparamagnetic Iron Oxide Nanoparticles: Synthesis,Characterization, Functionalization,Size Separation,Magnetic Properties,and Biological Applications

For biomedical application of nanoparticles, the surface chemical functionality is very important to impart additional functions, such as solubility and stability in a physiological environment, and targeting specificity as an imaging probe and a drug carrier. Although polyethylene glycol (PEG) has been used extensively, here, it is proposed that hyperbranched polyglycerol (PG) is a good or even better alternative to PEG. Superparamagnetic iron oxide nanoparticles (SPIONs) prepared using a polyol method are directly functionalized with PG through ring‐opening polymerization of glycidol. The resulting SPION‐PG is highly soluble in pure water (>40 mg mL^?1) and in a phosphate buffer solution (>25 mg mL^?1). Such high solubility enables separation of SPION‐PG according to size using size exclusion chromatography (SEC). The size‐separated SPION‐PG shows a gradual increase in transverse relaxivity (r₂) with increasing particle size. For biological application, SPION‐PG is functionalized through multistep organic transformations (–OH → –OTs (tosylate) → –N₃ → –RGD) including click chemistry as a key step to impart targeting specificity by immobilization of cyclic RGD peptide (Arg‐Gly‐Asp‐D ‐Tyr‐Lys) on the surface. The targeting effect is demonstrated by the cell experiments; SPION‐PG‐RGD is taken up by the cells overexpressing α_vβ₃‐integrin such as U87MG and A549.     

Myeloid‐Derived Suppressor Cell Membrane‐Coated Magnetic Nanoparticles for Cancer Theranostics by Inducing Macrophage Polarization and Synergizing Immunogenic Cell Death

A major challenge for traditional cancer therapy, including surgical resection, chemoradiotherapy, and immunotherapy, is how to induce tumor cell death and leverage the host immune system at the same time. Here, a myeloid‐derived suppressor cell (MDSC) membrane‐coated iron oxide magnetic nanoparticle (MNP@MDSC) to overcome this conundrum for cancer therapy is developed. In this study, MNP@MDSC demonstrates its superior performance in immune evasion, active tumor‐targeting, magnetic resonance imaging, and photothermal therapy (PTT)‐induced tumor killing. Compared with red blood cell membrane‐coated nanoparticles (MNPs@RBC) or naked MNPs, MNP@MDSCs are much more effective in active tumor‐targeting, a beneficial property afforded by coating MNP with membranes from naturally occurring MDSC, thus converting the MNP into “smart” agents that like to accumulate in tumors as the source MDSCs. Once targeted to the tumor microenvironment, MNPs@MDSC can act as a PTT agents for enhanced antitumor response by inducing immunogenic cell death, reprogramming the tumor infiltrating macrophages, and reducing the tumor's metabolic activity. These benefits, in combination with the excellent biocompatibility and pharmacological kinetics characteristics, make MNP@MDSC a promising, multimodal agent for cancer theranostics.     

A Charge Reversible Self‐Delivery Chimeric Peptide with Cell Membrane‐Targeting Properties for Enhanced Photodynamic Therapy

The cell membrane is the most important protective barrier in living cells and cell membrane targeted therapy may be a high‐performance therapeutic modality for tumor treatment. Here, a novel charge reversible self‐delivery chimeric peptide C₁₆–PRP–DMA is developed for long‐term cell membrane targeted photodynamic therapy (PDT). The self‐assembled C₁₆–PRP–DMA nanoparticles can effectively target to tumor by enhanced permeability and retention effect without additional carriers. After undergoing charge reverse in acidic tumor microenvironment, C₁₆–PRP–DMA inserts into the tumor cell membrane with a long retention time of more than 14 h, which is very helpful for in vivo applications. It is found that under light irradiation, the reactive oxygen species generated by the inserted C₁₆–PRP–DMA would directly disrupt cell membrane and rapidly induce cell necrosis, which remarkably increases the PDT effect in vitro and in vivo. This novel self‐delivery chimeric peptide with a long‐term cell membrane targeting property provides a new prospect for effective PDT of cancer.     

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.     

Platinum on Nanodiamond: A Promising Prodrug Conjugated with Stealth Polyglycerol,Targeting Peptide and Acid‐Responsive Antitumor Drug

In the field of nanomedicine, nanoparticles with various functions are required for in vivo applications such as biomedical imaging and drug delivery. Therefore, chemical functionalization of nanoparticles has been extensively investigated. Herein, nanodiamond (ND) coated with polyglycerol (PG) and its derivatives is reported to impart good solubility in a physiological environment, a stealth nature to avoid nonspecific uptake, a targeting property to be taken up by a specific cell, and an acid‐responsive drug release property to kill cancer cells. ND is first grafted with PG and the resulting ND‐PG has a high solubility in physiological media. Since a large number of hydroxyl groups in PG provide scaffolds for further surface functionalization, the targeting RGD peptide and Pt‐based drug are immobilized to give ND‐PG‐RGD, ND‐PG‐Pt and ND‐PG‐RGD‐Pt. The ND with intrinsic fluorescence is also functionalized by PG and RGD to confirm cellular uptake and intracellular localization fluorescently. The results of the cell experiments indicate that PG coating shielded fND from the uptake by HeLa and U87MG cells. In contrast, fND‐PG‐RGD is taken up by U87MG, not HeLa cells, exhibiting high targeting efficacy. When ND‐PG‐RGD‐Pt is applied, U87MG is selectively killed against HeLa. The multi‐functional ND is a promising prodrug in targeting chemotherapy.