Amino-Functionalized Silica Nanoparticles: In Vitro Evaluation for Targeted Delivery and Therapy of Pancreatic Cancer

We report a method of synthesis and optimization of amino-functionalized silica nanoparticles (SiNPs) and their in vitro evaluation as targeted delivery vehicles for the potential treatment of pancreatic cancer. SiNPs can efficiently encapsulate doxorubicin and can be attached to a targeting moiety such as anti-Claudin-4 (CLN4). The preferential uptake in pancreatic cancer cells, where CLN4 is overexpressed, of SiNPs when conjugated to CLN4 antibody (compared to nonconjugated SiNPs) was confirmed by confocal microscopy. SiNPs encapsulating doxorubicin had greater efficacy in MTT assays than free doxorubicin, and when conjugated to CLN4, the efficacy was dramatically increased (at 1 μM). No apparent carrier toxicity was observed when void SiNPs were used. SiNPs carrying a chemotherapeutic drug have the potential to be used as a targeted therapy for lethal cancers, such as pancreatic cancer. Also, incorporation of fluorescent probes in these SiNPs creates the possibility of their use as an imaging probe for diagnostic purposes

Targeted delivery of cisplatin to tumor xenografts via the nanoparticle component of nano-diamino-tetrac

Aim: Nano-diamino-tetrac (NDAT) targets a receptor on integrin alpha v beta 3; alpha v beta 3 is generously expressed by cancer cells and dividing endothelial cells and to a small extent by nonmalignant cells. The tetrac (tetraiodothyroacetic acid) of NDAT is covalently bound to a poly(lactic-co-glycolic acid) nanoparticle that encapsulates anticancer drugs. We report NDAT delivery efficiency of cisplatin to agent-susceptible urinary bladder cancer xenografts. Materials & methods: Cisplatin-loaded NDAT (NDAT-cisplatin) was administered to xenograft-bearing nude mice. Tumor size response and drug content were measured. Results: Intratumoral drug concentration was up to fivefold higher (p NDAT without cisplatin > cisplatin alone. Conclusion: NDAT markedly enhances cisplatin delivery to urinary bladder cancer xenografts and increases drug efficacy.NanoPharmaceuticals LLC (NY, USA)NanoPharmaceuticals LL

Tetraiodothyroacetic acid (Tetrac) and nanoparticulate tetrac arrest growth of medullary carcinoma of the thyroid

Context: Tetraiodothyroacetic acid (tetrac) blocks angiogenic and tumor cell proliferation actions of thyroid hormone initiated at the cell surface hormone receptor on integrin alpha v beta 3. Tetrac also inhibits angiogenesis initiated by vascular endothelial growth factor and basic fibroblast growth factor. Objective: We tested antiangiogenic and antiproliferative efficacy of tetrac and tetrac nanoparticles (tetrac NP) against human medullary thyroid carcinoma (h-MTC) implants in the chick chorioallantoic membrane (CAM) and h-MTC xenografts in the nude mouse. Design: h-MTCcells were implanted in the CAM model (n = 8 per group); effects of tetrac and tetrac NP at 1 mu g/CAM were determined on tumor angiogenesis and tumor growth after 8 d. h-MTC cells were also implanted sc in nude mice (n = 6 animals per group), and actions on established tumor growth of unmodified tetrac and tetrac NP ip were determined. Results: In the CAM, tetrac and tetrac NP inhibited tumor growth and tumor-associated angiogenesis. In the nude mouse xenograft model, established 450-500 mm(3) h-MTC tumors were reduced in size over 21 d by both tetrac formulations to less than the initial cell mass (100 mm(3)). Tumor tissue hemoglobin content of xenografts decreased by 66% over the course of administration of each drug. RNA microarray and quantitative real-time PCR of tumor cell mRNAs revealed that both tetrac formulations significantly induced antiangiogenic thrombospondin 1 and apoptosis activator gene expression. Conclusions: Acting via a cell surface receptor, tetrac and tetrac NP inhibit growth of h-MTC cells and associated angiogenesis in CAM and mouse xenograft models.Charitable Leadership Foundation/Medical Technology Acceleration ProgramPharmaceutical Research Institute of Albany College of Pharmac

Alpha v beta 3 integrin antagonists enhance chemotherapy response in an orthotopic pancreatic cancer model

Pancreatic cancer decreases survival time and quality of life because of drug resistance and peripheral neuropathy during conventional treatment. This study was undertaken to investigate whether alpha v beta 3 integrin receptor antagonist compounds NDAT and XT199 can suppress the development of cisplatin resistance and cisplatin-induced peripheral neuropathy in an orthotopic pancreatic SUIT2-luc cancer cell mouse model. Anticancer effects of these compounds and their combination with cisplatin were assessed in this tumor mouse model with bioluminescent signaling and histopathology, and a cytokine assay was used to examine expression of inflammatory cytokines IL-1 beta, IL-6, IL-10, and TNF-alpha from plasma samples. To determine the neuroprotective effects of the compounds on cisplatin-induced peripheral neuropathy, behavioral hind-limb posture of the mice was evaluated. The combination therapy of NDAT or XT199 with cisplatin elicited greater inhibition of tumor growth and increased tumor necrosis compared to cisplatin alone. NDAT and XT199 in combination with cisplatin significantly decreased expression of pro-inflammatory cytokines IL-1 beta, IL-6, and TNF-alpha and significantly increased expression of anti-inflammatory cytokine IL-10 in comparison to cisplatin alone. Cisplatin-treated groups showed stocking-glove hind-limb posture, whereas NDAT and XT199 with cisplatin-treated groups displayed normal hind-limb posture. Results clearly suggest that NDAT and XT199 treatment with cisplatin that inactivates NF-kappa B may contribute to increased antitumor and anti-inflammatory efficacy as well as alleviate cisplatin-mediated loss of motor function in this pancreatic tumor mouse model.Pharmaceutical Research Institute at Albany College of Pharmacy Health and Science

Nanoparticles and cancer therapy: A concise review with emphasis on dendrimers

Dhruba J Bharali, Marianne Khalil, Mujgan Gurbuz, Tessa M Simone, Shaker A MousaPharmaceutical Research Institute at Albany College of Pharmacy, Rensselaer, NY, USAAbstract: The emergence of nanotechnology has had a profound effect on many areas of healthcare and scientific research. Having grown exponentially, the focus of nanotechnology has been on engineering diversified novel applications that even go beyond therapeutic activity; nanotechnology also offers the ability to detect diseases, such as cancer, much earlier than ever imaginable. Often, patients diagnosed with breast, lung, colon, prostate, and ovarian cancer have hidden or overt metastatic colonies. With the advent of diagnostic nanotechnology, these numbers are expected to greatly diminish. This review provides a brief description of nanoparticle (liposome, quantum dot, and dendrimer)-mediated cancer therapy in the last decade with an emphasis on the development and use of dendrimers in cancer therapeutics.Keywords: nanoparticles, dendrimer, quantum dots, liposom