RESUMO
Pancreatic Ductal Adenocarcinoma (PDA) is a highly metastatic tumor, and the liver is its first target, which restricts the use of medications. PDA is considered one of the most aggressive types of cancer in the world, with an extremely short survival time, depending on the stage of diagnosis. In non-surgical cases, chemotherapy alternatives are only effective in 40% to 60% of patients. The low efficiency of treatments occurs mainly due to the complex microenvironment in PDA, leading to chemoresistance to treatments and making it difficult to reach the affected tissue. A very important histological characteristic of PDA is the extremely dense stroma, which leads to low vascularization of tumor tissue. Consequently, the stroma environment causes less drug accumulation in tumor cells, even of selective and/or targeted drugs. Overcoming the stroma's microenvironment is a major challenge for therapies. Moreover, specific genes lead to direct chemoresistance in PDA due to their high progression. In this scenario, nanotechnology appears as an alternative to overcome these clinical challenges concerning two distinct ways: acting on the stroma or/and acting directly on the pancreatic tumor cells. Thus, this review aimed to highlight advances in the application of nanotechnology aiming to open up new landscapes against PDA. There are a huge number of nanoparticles carrying drugs in preclinical and clinical trials for the effective treatment of PDA. These works have been discussed, and based on the current scenario, the future prospects for an efficient treatment of PDA have been proposed.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Pâncreas , Neoplasias Pancreáticas/tratamento farmacológico , Microambiente TumoralRESUMO
L-asparaginase or ASNase (L-asparagine aminohydrolase, E.C.3.5.1.1) is an enzyme clinically accepted as an antitumor agent to treat acute lymphoblastic leukemia (ALL) and lymphosarcoma through the depletion of L-asparagine (L-Asn) resulting in cytotoxicity to leukemic cells. ASNase is also important in the food industry, preventing acrylamide formation in processed foods. Several quantification techniques have been developed and used for the measurement of the ASNase activity, but standard pharmaceutical quality control methods were hardly reported, and in general, no official quality control guidelines were defined. To overcome this lack of information and to demonstrate the advantages and limitations, this work properly compares the traditional colorimetric methods (Nessler; L-aspartic acid ß-hydroxamate (AHA); and indooxine) and the high-performance liquid chromatography (HPLC) method. A comparison of the methods using pure ASNase shows that the colorimetric methods both overestimate (Nessler) and underestimate (AHA and indooxine) the ASNase activity when compared to the values obtained with HPLC, considered the most precise method as this method monitors both substrate consumption and product formation, allowing for overall mass-balance. Correlation and critical analysis of each method relative to the HPLC method were carried out, resulting in a demonstration that it is crucial to select a proper method for the quantification of ASNase activity, allowing bioequivalence studies and individualized monitoring of different ASNase preparations. Graphical abstract á .