New Avenues for Nanoparticle-Related Therapies

Abstract

Development of nanoparticle-based drug delivery systems has been attempted for the treatment of cancer over the past decade. The enhanced permeability and retention (EPR) effect is the major mechanism to passively deliver nanodrugs to tumor tissue. However, a recent systematic review demonstrated limited success of these studies, with the clearance of nanoparticles by the mononuclear phagocytic system (MPS) being a major hurdle. Herein, we propose that nanotechnologists should reconsider their research focuses, aiming for therapeutic targets other than cancer. Treatments for diseases that do not (or less) rely on EPR should be considered, such as active targeting or MPS evasion systems. For example, systemic delivery of drugs through intravenous injection can be used to treat sepsis, multi-organ failure, metabolic disorders, blood diseases, immune and autoimmune diseases, etc. Local delivery of nanodrugs to organs such as the lung, rectum, or bladder may enhance the local drug concentration with less clearance via MPS. In transplant settings, ex vivo organ perfusion provides a new route to repair injury of isolated organs in the absence of MPS. Based on a similar concept, chemotherapy with in vivo lung perfusion techniques and other isolated organ perfusion provides opportunities for cancer therapy.

Current status and contemporary approaches to the discovery of antitumor agents from higher plants

“…Targets of tumors that have been discovered in vivo include antigens found in the tumor, cell surface receptors that have been assimilated, and tumor vessel formation (Sahoo et al, 2004;Santra et al, 2005;Smith et al, 2008). To date, precision delivery has been has not been translated successfully into the clinic even though it has been studied in vivo, so it may be necessary to re-evaluate how nanoparticles are being used (Lammers et al, 2008;Zhao and Liu, 2018). Hence, directed drug delivery without an increase in overall localized drug accumulation is an important area of development for selective targeting strategies to safely deliver the drug at the target tissue, particularly for cancer treatment (Kirpotin et al, 2006;Park et al, 2004).…”

Local administration of submicron particle paclitaxel to solid carcinomas induces direct cytotoxicity and immune-mediated tumoricidal effects without local or systemic toxicity: preclinical and clinical studies

“…Various particle-based drug delivery systems are being developed for treatment of cancer [ 2 , 3 ]. However, success of many systems is limited by ineffective delivery to tumor sites as well as abbreviated drug residence due, in part, to the clearance of particles by the immune system [ 4 ].…”

Local Injection of Submicron Particle Docetaxel is Associated with Tumor Eradication, Reduced Systemic Toxicity and an Immunologic Response in Uro-Oncologic Xenografts

“…Nanoparticle-based drug delivery systems are among those being developed for treatment of cancer. However, success of these systems may be limited by their systemic administration and abbreviated tumor residence due, in part, to the clearance of nanoparticles by phagocytes [2]. Nanoparticle taxanes (NanoDoce ® and NanoPac ® ; CritiTech, Inc., Lawrence, KS, USA) were developed to increase intratumoral drug residence time through local delivery of submicron particles.…”