4/17/2023 0 Comments Ronnie coleman stem cell treatmentOwing to their physicochemical properties, (in)organic NMs can enhance the specific delivery of pharmaceutical agents to the tumor, either passively or by stimulated (externally triggered) release. Inorganic NMs are thus mainly used as contrast agents for magnetic resonance imaging (MRI) and are currently undergoing clinical trials for different applications such as thermal ablation of tumors and intraoperative sentinel lymph node imaging. (8−11) Translation of inorganic NMs into the clinic has been more limited, despite major successes on a preclinical level, (12) due to their lower biocompatibility and lack of knowledge and consensus pertaining to their safety and long-term deposition in different organs such as the liver and spleen. (3−7) Intravenously delivered organic NMs are mainly aimed at two specific applications: the delivery of small molecule drugs for cancer treatment ( i.e., breast, melanoma, head and neck, etc.) and gene therapy. Because of their high biocompatibility and reduced long-term side effects, organic NMs have been most successful in their translation into the clinic and are mainly being developed for applications like vaccination, long-lasting depot delivery systems, hemostasis, and topical agents for systemic delivery through the skin. (3) The therapeutic and diagnostic NMs can generally be classified into two categories: organic NMs ( i.e., liposomes, polymeric, micelles, etc.) and inorganic NMs ( i.e., iron oxide, gold, silica, etc.) ( Figure 1). (2)įor cancer therapy and diagnosis, various NMs have already been approved for clinical use, and many more are currently undergoing clinical trials. (2) Through our increased understanding of bionano interactions in combination with the rapid developments and in-depth knowledge gained in several medical fields such as oncology, research groups have been able to exploit the various unique properties of NMs to enhance therapeutic and diagnostic outcomes in cancer research and clinical use. As a result, various studies have focused on the interactions of NMs with their biological environment, aiming at elucidating which particular aspects of the NMs trigger which exact biological response. (1) While NMs have been mostly investigated within the electronic and industrial fields, the unique properties of NMs render them ideally suited to be explored in a wide variety of biomedical applications. It owes its success to the highly multidisciplinary nature of the field itself, bridging physics and chemistry expertise in nanomaterial (NM) synthesis and characterization with expertise in biology and medicine for functional applications. The application of nanotechnology for medical purposes, also known as nanomedicine, is a relatively novel field that has been gaining increasing interest over the years. We discuss the strengths and shortcomings of these different strategies and suggest combinatorial approaches as the ideal path forward. In this review, we provide a short overview of the EPR and mechanisms to enhance it, after which we focus on alternative delivery strategies that do not solely rely on EPR in itself but can offer interesting pharmacological, physical, and biological solutions for enhanced delivery. Furthermore, the role of the EPR effect has been called into question, where it has been suggested that NMs enter the tumor via active mechanisms and not through the endothelial gaps. Recent studies have shown that despite many efforts to employ the EPR effect, this process remains very poor. This phenomenon is made possible due to the leaky tumor vasculature through which NMs can leave the bloodstream, traverse through the gaps in the endothelial lining of the vessels, and enter the tumor. Classically, scientists have tried to improve NM delivery by employing passive or active targeting strategies, making use of the so-called enhanced permeability and retention (EPR) effect. Nanomaterial (NM) delivery to solid tumors has been the focus of intense research for over a decade.
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