For early cancer diagnosis and treatment, a nanocarrier system is designed and developed with key components uniquely structured at nanoscale according to medical requirements. For imaging, quantum dots with emissions in the near-infrared range (∼800 nm) are conjugated onto the surface of a nanocomposite consisting of a spherical polystyrene matrix (∼150 nm) and the internally embedded, high fraction of superparamagnetic Fe(3)O(4) nanoparticles (∼10 nm). For drug storage, the chemotherapeutic agent paclitaxel (PTX) is loaded onto the surfaces of these composite multifunctional nanocarriers by using a layer of biodegradable poly(lactic-co-glycolic acid) (PLGA). A cell-based cytotoxicity assay is employed to verify successful loading of pharmacologically active drug. Cell viability of human, metastatic PC3mm2 prostate cancer cells is assessed in the presence and absence of various multifunctional nanocarrier populations using the MTT assay. PTX-loaded composite nanocarriers are synthesized by conjugating anti-prostate specific membrane antigen (anti-PSMA) for targeting. Specific detection studies of anti-PSMA-conjugated nanocarrier binding activity in LNCaP prostate cancer cells are carried out. LNCaP cells are targeted successfully in vitro by the conjugation of anti-PSMA on the nanocarrier surfaces. To further explore targeting, the nanocarriers conjugated with anti-PSMA are intravenously injected into tumor-bearing nude mice. Substantial differences in fluorescent signals are observed ex vivo between tumor regions treated with the targeted nanocarrier system and the nontargeted nanocarrier system, indicating considerable targeting effects due to anti-PSMA functionalization of the nanocarriers.
A specially designed carbon nanotube (CNT) is developed for use in the early detection and treatment of cancer. The key functionalities for biomedical diagnosis and drug delivery are incorporated into the CNTs. In vivo imaging of live mice is achieved by intravenously injecting quantum dot (QD)‐conjugated CNT for the first time. With near infrared emission around 752 nm, the CNT with surface‐conjugated QD (CNT‐QD) exhibit a strong luminescence for non‐invasive optical in vivo imaging. CNT surface modification is achieved by a plasma polymerization approach that deposited ultra‐thin acrylic acid or poly(lactic‐co‐glycolic acid) (PLGA) films (∼3 nm) onto the nanotubes. The anticancer agent paclitaxel is loaded at 112.5 ± 5.8 µg mg−1 to PLGA‐coated CNT. Cytotoxicity of this novel drug delivery system is evaluated in vitro using PC‐3MM2 human prostate carcinoma cells and quantified by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The in vivo distribution determined by inductively coupled plasma mass spectrometry (ICP‐MS) indicates CNT‐QD uptake in various organs of live animals.
This article reviews advances in the design and development of multifunctional carbon-based and/or magnetic nanoparticle systems (or simply 'nanocarriers') for early cancer diagnosis and spatially and temporally controlled therapy. The critical issues in cancer diagnosis and treatment are addressed based on novel nanotechnologies such as real-time in-vivo imaging, drug storage and release, and specific cancer-cell targeting. The implementation of nanocarriers into animal models and the subsequent effectiveness in treating tumors is also reviewed. Recommendations for future research are given.
Triphenylphosphonium-fluorochromes (TPP-fluorochromes) are a new class of spectrally variable, mitochondrially targeted probes, with an [(18)F] labeling option which, when enabled, allows imaging of a cardiac perfusion deficit using PET/CT.
Heat induced radiolabeling (HIR) yielded 89Zr-Feraheme (FH) nanoparticles (NPs) used to determine NP pharmacokinetics (PK) by PET. Standard uptake values indicated a fast hepatic uptake that corresponded to blood clearance and a second, slow uptake process by lymph nodes and spleen. By cytometry, NPs were internalized by circulating monocytes and monocytes in vitro. Using an IV injection of HIR 89Zr-FH (rather than in vitro cell labeling), PET/PK provided a view of monocyte trafficking, a key component of the immune response.
It has been a challenging task to develop nontoxic nanoprobes for targeted-imaging and selective therapy of prostate cancer. Herein, fluorescent superparamagnetic nanoparticles with a diameter of 50 nm were conjugated with single-chain Fv antibody against γseminoprotein. The resultant nanoprobes showed highly selective targeting, fluorescent imaging, and magnetic resonance imaging. The cytotoxicity effects were investigated on the prostate cancer cells and solid tumors under in vitro alternating magnetic field irradiation. It was found that the as-prepared nanoprobes did not show signs of toxicity within the used maximal dosage. It was also observed that the tumors implanted in nude mice were significantly reduced in size and disappeared gradually due to thermal treatment. The lifespan of post-therapeutic mice loaded with prostate cancer was considerable prolonged. High-performance singlechain Fv antibody against γ-seminoprotein-conjugated fluorescent magnetic nanoparticles may have great potential in applications such early detection and localized thermal therapy of prostate cancer.
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