Engineering Tumor-Targeting Nanoparticles as Vehicles for Precision Nanomedicine

Abstract

As a nascent and emerging field that holds great potential for precision oncology, nanotechnology has been envisioned to improve drug delivery and imaging capabilities through precise and efficient tumor targeting, safely sparing healthy normal tissue. In the clinic, nanoparticle formulations such as the first-generation Abraxane ® in breast cancer, Doxil ® for sarcoma, and Onivyde ® for metastatic pancreatic cancer, have shown advancement in drug delivery while improving safety profiles. However, effective accumulation of nanoparticles at the tumor site is suboptimal due to biological barriers that must be overcome. Nanoparticle delivery and retention can be altered through systematic design considerations in order to enhance passive accumulation or active targeting to the tumor site. In tumor niches where passive targeting is possible, modifications in the size and charge of nanoparticles play a role in their tissue accumulation. For niches in which active targeting is required, precision oncology research has identified targetable biomarkers, with which nanoparticle design can be altered through bioconjugation using antibodies, peptides, or small molecule agonists and antagonists. This review is structured to provide a better understanding of nanoparticle engineering design principles with emphasis on overcoming tumor-specific biological barriers.

Nanomedicine review: clinical developments in liposomal applications

“…Liposomes are bilayer spherical vesicles composed by phospholipids and cholesterol that in water create at least one lipid bilayer surrounding an aqueous core, which may encapsulate both hydrophilic drugs (e.g., Doxil ® , encapsulated doxorubicin in the aqueous core) and hydrophobic compounds (e.g., AmBisome ® , trapped amphotericin B) immersed in the lamellae by Van der Waals forces (Senapati et al 2018;Gonda et al 2019;Gao et al 2018), see Fig. 2.…”

“…enhanced solubility and stability of drugs in the organism (Medina-Alarcón et al 2017;Ventola 2017). All these advantages have been reached by using drug delivery systems with 1-100 nm diameter nanoparticles, where a large surface leads to an increase in cellular interactions and multiple alterations of surface properties (Ud Din et al 2017;Senapati et al 2018;Gonda et al 2019). Moreover, by co-delivering multiple drugs, treatments with NPs have also facilitated synergistic therapies and avoided drug resistance (Casals et al 2017).…”

“…They still represent a large proportion of clinical-stage nanotherapeutics (Shi et al 2017;Bourquin et al 2018) due to their biodegradable, biocompatible, non-toxic, and non-immunogenic composition (Bozzuto and Molinari 2015;Zamani et al 2018). The amphiphilic phospholipid bilayer of liposomes has close resemblance to the mammalian cell membrane, enabling efficient interactions between liposomes and cell membrane and subsequently effective cellular uptake (Gonda et al 2019). In addition, liposomes may be added with ligands to increase efficiency and specifically target damaged cells, thus improving liposome pharmacokinetics and their ability to pass through target membranes, reaching high concentrations inside cells while reducing toxicity and enhancing treatment efficacy (Li et al 2014;Ud Din et al 2017;Zamani et al 2018;Hussain et al 2017;Lombardo et al 2016;Fouladi et al 2017;Maranhão et al 2017;Miller et al 2016).…”

“…The most commonly investigated nanoparticles are phospholipids-based carriers, micelles, polymeric nanoparticles based on poly(lactide-coglycolide) (PLGA), polybutylcyanoacrylate, poly(isohexyl cyanoacrylate), poly(amine-co-ester), chitosan nanoparticles (Chaudhuri and Straubinger 2019;van Rijt et al 2014), cellulose nanocrystals systems (Mohanta et al 2019), viral vectors (Gomes et al 2017), self-assemble proteins (Colton et al 2014), carbon nanotubes (Kaur et al 2019), dendrimers (Hudson 2001), core-shell and metallic NPs (Wu et al 2008), Fig. 1.…”

“…1. However, for nanomaterial-based therapeutics, liposomes have been the most successful formulation for clinical application to date (Gonda et al 2019), and the sterically stabilized liposomal formulations currently dominate the clinical landscape with FDA-approved products (Chaudhuri and Straubinger 2019). The success of liposomes in clinics is based on their versatility and their characteristics, such as their structural similarity to mammalian cell membranes and their capability to encapsulate either hydrophobic or hydrophilic drugs (Gonda et al 2019), among the other features described above.…”