Browsing by Author "Zhang, Jianfei"

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    Assembly of Bio-Nanoparticles for Double Controlled Drug Release
    Huang, Wei; Zhang, Jianfei; Dorn, Harry C.; Zhang, Chenming (PLOS, 2013-09-06)
    A critical limiting factor of chemotherapy is the unacceptably high toxicity. The use of nanoparticle based drug carriers has significantly reduced the side effects and facilitated the delivery of drugs. Source of the remaining side effect includes (1) the broad final in vivo distribution of the administrated nanoparticles, and (2) strong basal drug release from nanoparticles before they could reach the tumor. Despite the advances in pH-triggered release, undesirable basal drug release has been a constant challenge under in vivo conditions. In this study, functionalized single walled carbon nanohorn supported immunoliposomes were assembled for paclitaxel delivery. The immunoliposomes were formulated with polyethylene glycol, thermal stable and pH sensitive phospholipids. Each nanohorn was found to be encapsulated within one immunoliposome. Results showed a highly pH dependent release of paclitaxel in the presence of serum at body temperature with minimal basal release under physiological conditions. Upon acidification, paclitaxel was released at a steady rate over 30 days with a cumulative release of 90% of the loaded drug. The drug release results proved our hypothesized double controlled release mechanism from the nanoparticles. Other results showed the nanoparticles have doubled loading capacity compared to that of traditional liposomes and higher affinity to breast cancer cells overexpressing Her2 receptors. Internalized nanoparticles were found in lysosomes.
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    The Preparation, Functionalization and Biomedical Applications of Carbonaceous Nanomaterials
    Zhang, Jianfei (Virginia Tech, 2011-03-21)
    Carbon nanomaterials have attracted significant attention in the past decades for their unique properties and potential applications in many areas. This dissertation addresses the preparation, functionalization and potential biomedical applications of various carbonaceous nanomaterials. Trimetallic nitride template endohedral metallofullerenes (TNT-EMFs, M₃N@C₈₀, M = Gd, Lu, etc.) are some of the most promising materials for biomedical applications. Water-soluble Gd₃N@C₈₀ was prepared by the functionalization with poly(ethylene glycol) (PEG) and hydroxyl groups (Gd₃N@C₈₀[DiPEG(OH)ₓ]). The length of the PEG chain was tuned by changing the molecular weight of the PEG from 350 to 5000. The 1H magnetic resonance relaxivities of the materials were studied at 0.35 T, 2.4 T and 9.4 T. Their relaxivities were found to increase as the molecular weight of the PEG decreased, which is attributed to the increasing aggregate size. The aggregate sizes were confirmed by dynamic light scattering. In vivo study suggested that Gd3N@C₈₀[DiPEG(OH)x] was a good candidate for magnetic resonance imaging (MRI) contrast agents. Another facile method was also developed to functinalize Gd₃N@C₈₀ with both carboxyl and hydroxyl groups by reaction with succinic acyl peroxide and sodium hydroxide thereafter. The product was determined to be Gd₃N@C₈₀(OH)~₂₆(CH₂CH₂COOM)~₁₆ (M = Na, H) by X-ray photoelectron spectrometry. The Gd₃N@C₈₀(OH)~₂₆(CH₂CH₂COOM)~₁₆ also exhibited high relaxivity, and aggregates in water. The research on both pegylated and carboxylated Gd₃N@C₈₀ suggests that aggregation and rotational correlation time plays an important role in relaxation, and the relaxivities and aggregation of the water-soluble metallofullerenes can be tuned by varying the molecular weight of the functionality. TNT-EMFs can be encapsulated inside single-walled carbon nanotubes (SWNTs) to form "peapod" structures by heating the mixture of TNT-EMFs and SWNTs in a vacuum. The peapods were characterized by Raman spectrometry and transmission electron microscopy (TEM). The peapods were then functionalized with hydroxyl groups by a high speed vibration milling (HSVM) method in the presence of KOH. The functionalized Gd-doped peapods exhibited high relaxivites and had an additional advantage of "double carbon wall" protection of the toxic Gd atoms from possible leaking. The HSVM method was modified by using succinic acyl peroxide. The modified HSVM method could functionalize multi-walled carbon nanotubes (MWNT) and single-walled carbon nanohorns (SWNHs) with carboxyl groups. In the presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC), carboxylate MWNTs and SWNHs could be conjugated with CdSe/ZnS quantum dots (QDs). TNT-EMFs were also encapsulated inside SWNHs to form SWNH peapods. SWNH peapods were functionalized by the modified HSVM method and then were conjugated with CdSe/ZnS QDs. The peapods were characterized by TEM. In vitro and in vivo studies indicated that SWNH peapods could serve as a multimodal diagnostic agent: MRI contrast agent (Gd₃N@C₈₀ encapsulated), radio-active therapeutic agent (Lu₃N@C₈₀ encapsulated) and optical imaging agent (QDs).