Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments

Abstract

The ability to efficiently deliver a drug or gene to a tumor site is dependent on a wide range of factors including circulation time, interactions with the mononuclear phagocyte system, extravasation from circulation at the tumor site, targeting strategy, release from the delivery vehicle, and uptake in cancer cells. Nanotechnology provides the possibility of creating delivery systems where the design constraints are decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing tumor accumulation, and improving efficacy. The physico-chemical properties of nanoparticle-based delivery platforms introduce additional complexity associated with pharmacokinetics, tumor accumulation, and biodistribution. To assess the impact of nanoparticle-based delivery systems, we first review the design strategies and pharmacokinetics of FDA-approved nanomedicines. Next we review nanomedicines under development, summarizing the range of nanoparticle platforms, strategies for targeting, and pharmacokinetics. We show how the lack of uniformity in preclinical trials prevents systematic comparison and hence limits advances in the field.

Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with chitosan/alginate by layer by layer technology for antitumor applications

“…9,10 Owing to good biocompatibility properties, biodegradability, nontoxicity, nonimmunogenicity and sustained release properties, PLGA NPs have been widely used as drug delivery carriers for anticancer drugs. [11][12][13][14][15] PLGA is approved by the Food and Drug Administration and the European Medicines Agency for various drug delivery systems for human applications. 11 Several drugs (including dexamethasone, 5-fluorouracil and paclitaxel) have been successfully incorporated into PLGA.…”

Tailoring nanoparticle designs to target cancer based on tumor pathophysiology

“…However, to engineer an optimal nanoparticle delivery system for cancer targeting is more complicated and one needs to balance the particular function (i.e., payload and signal intensity), tumor interaction, and the tumor-competing organs for nanoparticle sequestration. Unfortunately, optimization of only the physicochemical properties of nanomaterials has reached an impasse whereby tumor targeting efficiency remains stagnated at 5% (6,39). In our work, we have alternatively approached tumor delivery from the biological perspective by characterizing the unique physiological changes that occur during tumor growth to tailor nanoparticles.…”

Nanocarrier drugs in the treatment of brain tumors

“…The RGD (Arg-Gly-Asp) oligopeptide is a component of the extracellular matrix protein fibronectin and promotes cell adhesion and regulates migration, growth, and proliferation. [25,40] RGD is known to serve as a recognition motif in multiple ligands for several different integrins. RGD-containing peptide can be internalized into cells by integrin-mediated endocytosis.…”

“…Strategies for active targeting of tumors usually involve targeting surface membrane proteins that are upregulated in cancer cells. [25] Targeting molecules are typically antibodies or their fragments, aptamers, small molecules, or oligopeptides. Nanoparticles coupled with surface ligands or antibodies can localize to tissue, expressing the associated receptors or antigens and improving delivery efficacy.…”