Translational Nano-Medicines: Targeted Therapeutic Delivery for Cancer and Inflammatory Diseases

Abstract

Abstract. With the advent of novel and personalized therapeutic approaches for cancer and inflammatory diseases, there is a growing demand for designing delivery systems that circumvent some of the limitation with the current therapeutic strategies. Nanoparticle-based delivery of drugs has provided means of overcoming some of these limitations by ensuring the drug payload is directed to the disease site and insuring reduced off-target activity. This review highlights the challenges posed by the solid tumor microenvironment and the systemic limitations for effective chemotherapy. It then assesses the basis of nanoparticle-based targeting to the tumor tissues, which helps to overcome some of the microenvironmental and systemic limitations to therapy. We have extensively focused on some of the tumor multidrug resistance mechanisms (e.g., hypoxia and aerobic glycolysis) that contribute to the development of multidrug resistance and how targeted nano-approaches can be adopted to overcome drug resistance. Finally, we assess the combinatorial approach and how this platform has been used to develop multifunctional delivery systems for cancer therapy. The review article also focuses on inflammatory diseases, the biological therapies available for its treatment, and the concept of macrophage repolarization for the treatment of inflammatory diseases.

Monocyte metabolic reprogramming promotes pro-inflammatory activity and Staphylococcus aureus biofilm clearance

“…Tuftsin is a peptide derived from the Fc portion of IgG, which has been shown to facilitate nanoparticle internalization by MФs through its interaction with Fc receptors [28]. Previous studies have utilized tuftsin-conjugated nanoparticles to deliver a variety of biomolecules to monocytes and MФs in the context of arthritis, HIV, and other inflammatory diseases [28,[35][36][37]. We utilized three nanoparticle types, namely Cy5 (C), Cy5/Tuftsin (CT), and Cy5/Tuftsin/Oligomycin (CTO), where the former two represented control formulations and all three harbored the Cy5 fluorochrome to identify nanoparticle localization in vivo (Table 1).…”

Remotely Triggered Nano-Theranostics For Cancer Applications

“…Nanotheranostics has rapidly progressed to include biocompatible and biodegradable, multifunctional and integrated nanoplatforms that encapsulate drugs and diagnostic agents 151 - 162 . Nanotheranostics may deliver chemo-, radio-, biologic-, immuno- or gene therapies, or some combinations of these agents.…”

Current Trends and Challenges in the Clinical Translation of Nanoparticulate Nanomedicines: Pathways for Translational Development and Commercialization

“…NNMs are intended to increase the therapeutic index of drugs (i.e., increase efficacy and/or reduce toxicity) by delivering them via various mechanisms: solubilization, passive targeting, active targeting, and triggered release (Figure 1 ). Nanoencapsulation gives the opportunity to protect fragile compounds that degrade easily in biological environments and to provide solubilization, i.e., to deliver compounds which have physicochemical properties that strongly limit their aqueous solubility and therefore systemic bioavailability (Talekar et al, 2015 ; Kim et al, 2016 ; Larsson et al, 2017 ; Mishra et al, 2017 ; Shajari et al, 2017 ). Targeted drug delivery and triggered release of NNMs have been shown to be beneficial for increasing the therapeutic index of compounds, by improving the in vivo fate of drug molecules such that more efficient delivery to the target site is achieved (to yield improved therapeutic effects) with less accumulation in many healthy body sites (to reduce toxicity).…”