Search

Purpose: Melanoma is an invasive and very aggressive skin cancer due to its multi-drug resistance that results in poor patient survival. There is a need to test new treatment approaches to improve therapeutic efficacy and reduce side effects of conventional treatments., Methods: PLA/PVA nanoparticles carrying both Dacarbazine and zinc phthalocyanine was produced by double emulsion technique. The characterization was performed by dynamic light scattering and atomic force microscopy. In vitro photodynamic therapy test assay using MV3 melanoma cells as a model has been performed. In vitro cell viability (MTT) was performed to measure cell toxicity of of nanoparticles with and without drugs using human endothelial cells as a model. The in vivo assay (biodistribution/tissue deposition) has been performed using radiolabeled PLA/PVA NPs., Results: The nanoparticles produced showed a mean diameter of about 259 nm with a spherical shape. The in-vitro photodynamic therapy tests demonstrated that the combination is critical to enhance the therapeutic efficacy and it is dose dependent. The in vitro cell toxicity assay using endothelial cells demonstrated that the drug encapsulated into nanoparticles had no significant toxicity compared to control samples. In-vivo results demonstrated that the drug loading affects the biodistribution of the nanoparticle formulations (NPs). Low accumulation of the NPs into the stomach, heart, brain, and kidneys suggested that common side effects of Dacarbazine could be reduced., Conclusion: This work reports a robust nanoparticle formulation with the objective to leveraging the synergistic effects of chemo and photodynamic therapies to potentially suppressing the drug resistance and reducing side effects associated with Dacarbazine. The data corroborates that the dual encapsulated NPs showed better in-vitro efficacy when compared with the both compounds alone. The results support the need to have a dual modality NP formulation for melanoma therapy by combining chemotherapy and photodynamic therapy.

Purposes: Senescence is an inevitable and irreversible process, which may lead to loss in muscle and bone density, decline in brain volume and loss in renal clearance. Although aging is a well-known process, few studies on the consumption of nanodrugs by elderly people were performed., Methods: We evaluated three different nanosystems: i) carbon based nanosystem (Graphene Quantum Dots, GQD), ii) polymeric nanoparticles and mesoporous silica (magnetic core mesoporous silica, MMSN). In previous studies, our group has already characterized GQD and MMSN nanoparticles by dynamic light scattering analysis, atomic force microscopy, transmission electron microscopy, X-ray diffraction, Raman analysis, fluorescence and absorbance. The polymeric nanoparticle has been characterized by AFM and DLS. All the nanosystems were radiolabeled with 99 m-Tc by. The in vivo biodistribution/tissue deposition analysis evaluation was done using elder (PN270) and young (PN90) mice injected with radioactive nanosystems., Results: The nanosystems used in this study were well-formed as the radiolabeling processes were stable. Biodistribution analysis showed that there is a decrease in the uptake of the nanoparticles in elder mice when compared to young mice, showing that is necessary to increase the initial dose in elder people to achieve the same concentration when compared to young animals., Conclusion: The discrepancy on tissue distribution of nanosystems between young and elder individuals must be monitored, as the therapeutic effect will be different in the groups. Noteworthy, this data is an alarm that some specific conditions must be evaluated before commercialization of nano-drugs. Graphical Abstract Changes between younger and elderly individuals are undoubtedly, especially in drug tissue deposition, biodistribution and pharmacokinetics. The same thought should be applied to nanoparticles. A comprehensive analysis on how age discrepancy change the biological behavior of nanoparticles has been performed.

Purpose: Pancreatic Polypeptide-secreting tumor of the distal pancreas (PPoma) is a rare, difficult and indolent type of cancer with a survival rate of 5-year in only 10% of all cases. The PPoma is classified as a neuroendocrine tumor (NET) not functioning that overexpresses SSTR 2 (somatostatin receptor subtype 2). Thus, in order to improve the diagnosis of this type of tumor, we developed nanoparticulate drug carriers based on poly-lactic acid (PLA) polymer loaded with octreotide and radiolabeled with Technetium-99 m ( 99m Tc)., Methods: PLA/PVA octreotide nanoparticles were developed by double-emulsion technique. These nanoparticles were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) and radiolabeled with 99mTc by the direct via forming 99m Tc-PLA/PVA octreotide nanoparticles. The safety of these nanosystems was evaluated by the MTT cell toxicity assay and their in vivo biodistribution was evaluated in xenografted inducted animals., Results: The results showed that a 189 nm sized nanoparticle were formed with a PDI of 0,097, corroborating the monodispersive behavior. These nanoparticles were successfully radiolabeled with 99mTc showing uptake by the inducted tumor. The MTT assay corroborated the safety of the nanosystem for the cells., Conclusion: The results support the use of this nanosystem ( 99m Tc-PLA/PVA octreotide nanoparticles) as imaging agent for PPoma. Graphical Abstract Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma) Radiolabeled Nanoparticles for Imaging.

Purpose: The purpose of this article was to develop, characterize and test (in vivo) dacarbazine microparticles that may be labeled with 99mTc and Ra-223 for both use: diagnostic and therapy of metastatic melanoma., Methods: We developed by double emulsion solvent evaporation methodology the microparticle. The characterization has been done using, Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM). The labeling with 99mTc and Ra-223 has been done by the direct labeling process. Also the formulation has been tested pre-clinically using Balb/c mice inducted with melanoma, performing the the biodistribution and planar imaging. Cytotoxicity evaluation was also done in M3 V cell line. In order to understand the safety aspects of the microparticles, microbiological study (endotoxin and sterility) has been done. Finally, planar imaging was performed to evaluate the diagnosing aspect., Results: The results showed that a 559 nm microparticles was obtained with a spherical shape. The labeling process with 99mTc reached over 90% of efficacy. On the other hand, the labeling process with Ra-223 showed a 70% efficacy. The results in inducted animals demonstrated that the microparticles were able to reach the tumor with a high rate (20%). Also demonstrated a low recognition by the Mononuclear Phagocytic System. The cytotoxicity and the microbiological control, corroborates the safety aspect of these microparticles., Conclusion: The planar image and the possible labeling with Ra-223, corroborates the use as a theragnostic agent for imaging and therapy of Metastatic Melanoma.