Abstract
Nanoparticle (NP)-mediated drug delivery (NMDD) for active targeting of diseases is a primary goal of nanomedicine. NPs have much to offer in overcoming the limitations of traditional drug delivery approaches, including off-target drug toxicity and the need for the administration of repetitive doses. In the last decade, one of the main foci in NMDD has been the realization of NP-mediated drug formulations for active targeted delivery to diseased tissues, with an emphasis on cellular and subcellular targeting. Advances on this front have included the intricate design of targeted NP-drug constructs to navigate through biological barriers, overcome multidrug resistance (MDR), decrease side effects, and improve overall drug efficacy. In this review, we survey advancements in NP-mediated drug targeting over the last five years, highlighting how various NP-drug constructs have been designed to achieve active targeted delivery and improved therapeutic outcomes for critical diseases including cancer, rheumatoid arthritis, and Alzheimer’s disease. We conclude with a survey of the current clinical trial landscape for active targeted NP-drug delivery and how we envision this field will progress in the near future.
Highlights
One of the persistent challenges in therapeutic drug delivery is the targeted localization of maximal amounts of the therapeutic to the cellular/subcellular site of action in pathologically affected tissues
Advances on this front have included the intricate design of targeted NP-drug constructs to navigate through biological barriers, overcome multidrug resistance (MDR), decrease side effects, and improve overall drug efficacy
Our goal in this review is to provide a survey of recent advances in NMDD wherein the active targeting of NP-drug constructs to various cellular and subcellular (Scheme 1) locations has facilitated significant improvements in drug efficacy
Summary
One of the persistent challenges in therapeutic drug delivery is the targeted localization of maximal amounts of the therapeutic to the cellular/subcellular site of action in pathologically affected tissues. Our goal in this review is to provide a survey of recent advances in NMDD wherein the active targeting of NP-drug constructs to various cellular and subcellular (Scheme 1) locations (primarily to the nucleus and mitochondria of the disease-affected tissues/cells) has facilitated significant improvements in drug efficacy. Nguyen and colleagues reported methotrexate (MTX)-loaded polymeric NPs for SSTR-mediated targeted delivery [70] These NPs were decorated with lanreotide (LT), a synthetic analog of somatostatin, on the surface of the NPs comprised of a photosensitizing polymer, polyaniline (PANI), poly(lactic-co-glycolic acid) (PLGA), and DSPE-PEG. Cheng and colleagues prepared DOX-loaded MSNs that were coated with polydopamine (PDA) and poly(ethylene glycol)-folic acid (PEG-FA) for cervical cancer therapy This formulation showed ~2-fold higher uptake in HeLa cells with enhanced antitumor efficacy compared to non-targeted preparation [96]. This formulation showed both rapid detection of Aβ aggregates and mediated the disassembly of Aβ aggregates and inhibited Aβ-mediated toxicity in Caenorhabditis elegans
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