Nanomedicine systems that reduce the size of pancreatic tumors

Background Pancreatic ductal adenocarcinoma (PDAC), commonly known as pancreatic cancer, is among the leading causes of cancer-related deaths in the Western world, this due to the presentation of the disease at an advanced stage, early metastases and, in general, a very limited response to chemotherapy or radiotherapy [1]. PDAC is an aggressive tumor with a poor prognosis, as it is difficult to predict, detect and diagnose in early stages [2]. Recent advances in nanotechnology-based drug delivery systems have aimed to increase cellular absorption that allow nutrients to be obtained from normal cells that remain in the pancreatic gland, improving their permeability and drug retention or by functionalizing the surface of carriers. , improve the pharmacokinetics and effectiveness of anticancer drugs, which have helped potentiate the activity of specific agents for effective pancreatic cancer (PC) therapy [3][4]. One strategy to avoid macrophage phagocytosis is to functionalize the nanoparticle with the biocompatible and non-immunogenic hydrophilic polymer polyethylene glycol (PEG). This functionalization prevents the mobilization of opsonins on the surface of the nanoparticles that induce macrophages to recognize and remove the nanoparticle from the blood [5] . Polyethylene glycol (PEG) is produced from the polymerization of ethylene oxide, ethylene glycol or diethylene glycol in the presence of alkaline catalysts and the reaction ends by neutralizing the catalyst when the polymer reaches the desired molecular weight. In 2018, the anticancer drug, doxorubicin, conjugated to PEGylated nanotubes, was used , reducing the size of the tumor in mice. Release was measured over 42 days, and most were released during the first seven days and much lower in the following days [6], [7]. In 2019, a super paramagnetic formulation of curcumin iron oxide nanoparticles (SPION) (SP-CUR) was developed, which is a non-toxic bioactive anti-inflammatory/anticancer agent for better administration in tumors. Results in a male mouse model 6 to 8 weeks of age showed improved accumulation of SP-CUR in the pancreas, which potentiated gemcitabine (GEM) to reduce tumor growth rate and metastasis [8]. On the other hand, fucoidan (FCD) is a natural sulfated polysaccharide extracted from brown algae, which was included in the manufacture of a nanosystem through its interaction of polyelectrolytes with positively charged lactoferrin to improve its cellular absorption and internalization. In 2020, in vitro studies conducted on the PANCREATIC CANCER CELL LINE PANC-1 demonstrated superior cytotoxicity and inhibition of migration and invasion as a result of increased cell absorption and internalization [9], [10]. In addition, in vivo studies conducted in male mice revealed a greater reduction in tumor volume with a higher survival rate without noticeable signs of toxicity in the case of targeted drug-laden dual nanoparticles, compared to drug-laden or drug-laden nanoparticles without targeting active fractions [10]. In that same year, they used for active targeting the drug lactoferrin (LF) and hyaluronic acid, adding them to the surface of the nanoparticles through the coating technique layer by layer. In vivo studies revealed that the nanoparticles showed greater reduction in tumor volume with superior survival without any toxicity to the major organs [11]. Nanotechnology offers the resources to directly target the drug to the tumor site, thereby improving the therapeutic efficacy of current treatment modalities [12]. This review focuses on determining the most effective composition in tumour reduction, as well as the importance of nanotechnology for the treatment of pancreatic ductal adenocarcinoma (PDAC) and target site administration. Research Question Which nanomedicine system, targeting pancreatic cancer, has achieved the greatest reduction in tumor size in preclinical models? Inclusion criteria Studies involving preclinical models of progressive or metastatic pancreatic cancer. Preclinical studies where nanoparticles are combined with other drugs to reduce pancreatic tumor volume. Studies presenting the dose used, adverse events, overall survival, and progression-free survival of the formulation. Studies indicating any of the following preclinical events: tumor volume, antitumor activity, survival curve, dose administration times with treatment, cell absorption, tumor growth, apoptosis, cytotoxicity. Exclusion criteria Non-clinical research such as reviews. Records no written in English. Articles with date published prior to 2017. Studies that address another type of cancer. Phases of minor clinical trials of the same author or working group. Studies published in congress reports. General objective To determine the most effective regimen nanoparticles in reducing pancreatic cancer tumor volume in preclinical in vivo or in vitro models with disease progression and metastasis. Specific objectives To determine the optimal nanoparticle that enhances the decrease in tumor volume in pancreatic cells. To evaluate antitumor activity by incorporating nanoparticles into pancreatic tumor cells. To analyze articles containing preclinical studies of nanoparticles in combination with other drugs aimed at the treatment of PDAC. To analyze scientific articles that use the use of nanoparticles as the main treatment for pancreatic cancer. Unfortunately, pancreatic ductal adenocarcinoma remains one of the leading causes of death. Different biological barriers prevent the successful delivery of nanoformulations to target sites, limiting the effective therapeutic response. The reasonable combination of therapies with different mechanisms may bring the greatest hope for PDAC patients and have a major impact on the integrated pancreatic cancer treatment model since nanoparticles have the ability to deliver a variety of drugs to the tumor site. This systematic review could be useful as a basis for the potential development of multifunctional nanoparticles that allow the drug to be delivered to tumor cells in appropriate concentrations in pancreatic cancer, as well as its efficient therapy in reducing tumor volume. In this way, through the analysis of different preclinical events, obtained from the articles collected from databases with clinical research on cancer, it will be possible to determine the nanoparticle with the greatest reduction in tumor volume to improve anticancer activity demonstrating its effectiveness in the treatment of CP. Proposed methodology Selection of the databases, of those offered at the UACJ, for the search for research of interest in the subject of study: PubMed, ScienceDirect, EBSCO Host are proposed. Determinación de los términos de búsqueda y operadores booleanos. The following are proposed: (nanoparticles OR NP) AND (“pancreatic ductal adenocarcinoma” OR PDAC OR “Pancreatic cancer” OR “pancreatic tumor”) AND ("tumor volume"). Elaboration of a PRISMA flowchart for the screening and accounting of the articles to be included in the review. Search and selection of the tool for the critical evaluation of the included articles. Critical evaluation of articles. Tabulation of findings related to the use of nanoparticles and their effect on tumor volume reduction. Analysis of the results of the investigations to determine the characteristics of the nanoparticles that present greater effectiveness in reducing pancreatic tumor volume