3 - Frontiers in Nanoparticulate Approaches to Imaging and Photodynamic Therapy
Florida 2 10:00 - 12:00
|Chair(s): Jon Lovell|
10:00 Nanoparticle clusters for cancer imaging and therapy KV Sokolov*, The UT M.D. Anderson Cancer Center
Abstract: Synthesis of heterogeneous hybrid nanoparticles can be advantageous in a variety of biomedical applications. However, integration of multiple components in a single nanostructure is a challenging task. Most of the existing approaches to synthesis of hybrid nanoparticles require cumbersome multi-step protocols and result in nanostructures with limited tunability of physical and chemical properties. Here, we present a general idea of using controlled self-assembly of individual very small ca. 5 nm diameter nanoparticles into well-defined nanoclusters with desirable properties for in vivo applications. Two specific examples of this approach will be discussed: (1) synthesis of biodegradable plasmonic nanoparticles, and (2) magneto-plasmonic nanoclusters (MPNs) with a strong near-infrared (NIR) absorbance and a high magnetic moment in an external magnetic field. We demonstrated that self-assembled nanoclusters greatly improve sensitivity of MRI and photoacoustic imaging, magnetic cell separation and cell manipulation in an external magnetic field. Furthermore, biodegradable nanoclusters can dissociate into ca. 5 nm constituent particles under physiological condition that facilitates accelerated excretion from the body.
10:30 Ferritin-facilitated photodynamic therapy against cancer J Xie*, University of Georgia
Abstract: Photodynamic therapy is an emerging cancer treatment modality. Despite of the great promise, there is a lack of a reliable delivery vehicle for tumor targeted delivery of photosensitizers. Previous efforts have been focused on polymer- or liposome-based nanocarriers, which are often associated with a suboptimal drug loading rate and a large particle size. Our recent studies found that ferritin, a compact protein cage (~12 nm), can load photosensitizers such as zinc hexadecafluorophthalocyanine (ZnF16Pc) at high efficiency (~60wt%). Meanwhile, ferritins can be modified by either chemical or genetic methods to introduce targeting ligands to the particle surface. In particular, we've successfully introduced folic acid, RGD4C, and a FAP targeting scFv, to the surface of ferritins. By using these surface modified ferritins as carriers, we are able to selectively deliver ZnF16Pc to cancer cells, tumor endothelial cells, and tumor associated fibroblasts. With appropriate photoirradiation, the treatment leads to efficient tumor growth control, with minimal toxicity to the skin and other normal tissues. Compared with artificial carrier based delivery, the technology affords advantages such as low toxicity, low immunogenicity, and biodegradability and holds great promise in clinical translation.
11:00 Targeted Gold Nanoparticles for PDT Drug Delivery in Brain Tumors A-M Broome*, Medical University of South Carolina
; S Dixit, Medical University of South Carolina; Y Zhu, Medical University of South Carolina; A Moore, Medical University of South Carolina
Abstract: Therapeutic drug delivery across the blood-brain-barrier is not only inefficient but also nonspecific, thereby posing a major shortcoming in effective treatment of brain cancer. Widespread use of photodynamic therapy (PDT) as a localized treatment modality in brain tumor therapy has been partially hampered by non-targeted phototoxicity towards healthy tissue. Development of nanoparticles selectively targeted to cell surface receptors that can act as drug delivery vehicles is critical for improving the therapeutic responsiveness in inaccessible tumors, such as glioblastomas. Gold nanoparticles (Au NPs) provide an excellent platform with a surface that can be tailored to attach biomolecules for targeted drug delivery and biocompatible coatings that can efficiently encapsulate the hydrophobic photosensitizer drug, Pc 4, thereby reducing off-site cytotoxicity. Our research demonstrate a novel double targeted, noncovalent Au NP drug delivery agent, which selectively delivers drugs to brain tumors for PDT. Double-targeted Au NPs loaded with the drug silicon phthalocyanine (Pc 4) have been compared with previously studied single targeted Au NPs. More specific and efficient uptake is observed upon dual targeting. Upon activation of Pc 4 by PDT after delivery by the double-targeted Au NPs increased cell death is observed as compared to systemically delivered Pc 4.
11:30 Doxorubicin Encapsulated In Long Circulating Stealth Liposomes Conferred With Light-triggered Drug Release D Luo*, University at Buffalo, State University of New York
; KA Carter, University at Buffalo, State University of New York; A Razi, McMaster University; J Geng, University at Buffalo, State University of New York; S Shao, University at Buffalo, State University of New York; D Giraldo, University at Buffalo, State University of New York; U Sunar, Wright State University; J Ortega, McMaster University; JF Lovell, University at Buffalo, State University of New York
Abstract: Delivery of drugs at sites of target at therapeutically effective levels is a central challenge for drug delivery in cancer therapy. There is an increasing interest in designing liposomes and other type of nanoparticles that can release encapsulated drugs in response to external (e.g. light, heat, or ultrasound) or environmental triggers (e.g. pH, enzymes). Stealth liposomes can be used to extend the blood circulation times of encapsulated therapeutics. Inclusion of small amount (i. e. 2 mol. %) of porphyrin-phospholipid (PoP) imparted near infrared light-triggered release of doxorubicin (Dox) from stealth liposomes. The type and amount of PoP affected drug loading, serum stability and drug release induced by NIR light. Cholesterol and PEGylation were required for Dox loading, but slowed light-triggered release. By studying these factors we have developed Dox-loaded stealth liposomes which exhibit a long circulation time (half-life in mice: 21.9 h) and were stable in storage for months. Following intravenous injection and NIR irradiation, Dox deposition increased 7 fold in treated subcutaneous human pancreatic xenografts. Photo treatment induced mild tumor heating and complex tumor hemodynamics. A single chemo-phototherapy treatment with Dox-loaded stealth PoP liposomes (5-7mg/kg Dox) eradicated tumors while corresponding chemo- or photodynamic therapies were ineffective. A low dose 3 mg/kg Dox photo-treatment with stealth PoP liposomes was more effective than a maximum tolerated dose of free (7 mg/kg) or conventional long-circulating liposomal Dox (21 mg/kg). To our knowledge, Dox-loaded stealth PoP liposomes represent the first reported long-circulating nanoparticle capable of light-triggered drug release.