Design of Nanoparticle-Based Carriers for Targeted Drug Delivery

Abstract

Nanoparticles have shown promise as both drug delivery vehicles and direct antitumor systems, but they must be properly designed in order to maximize efficacy. Computational modeling is often used both to design new nanoparticles and to better understand existing ones. Modeled processes include the release of drugs at the tumor site and the physical interaction between the nanoparticle and cancer cells. In this article, we provide an overview of three different targeted drug delivery methods (passive targeting, active targeting and physical targeting), compare methods of action, advantages, limitations, and the current stage of research. For the most commonly used nanoparticle carriers, fabrication methods are also reviewed. This is followed by a review of computational simulations and models on nanoparticle-based drug delivery.

Keywords: cancer; multiscale modeling; nanoparticle design; self-assembly of nanoparticles; targeted drug delivery.

Fig. 1

Schematic contrast of drug biodistribution after injection of free drug (A) and drug-loaded NPs (B).

Fig. 2

Schematic of two types of amphiphilic nanoparticles, liposomes and micelles. Liposomes have a double layer and a hydrophilic core, while the core of micelles is hydrophobic.

Fig. 3

Structures of novel nanoparticles. A) Polyrotaxane NPs are assembled from cyclical molecules threaded around a long polymer chain. Hydrophilic ends are added to the chain in order to induce self-assembly. Drugs are then added to the finished NP. Adapted with permission from . B) Graphene functionalized with shielding molecules and ligands. Adapted with permission from . C) Carbon nanotube schematic. D) Dendrimer schematic. E) Metal-core photothermal NP schematic.

Fig. 4

Schematic representation of the disulfide cross-linked micelles formed by oxidization of self-assembled thiolated telodendrimer PEG^5k-Cys₄-L₈-CA₈ . Schematic representation of the telodendrimer pair [PEG^5k-(boronic acid or Catechol)₄-CA₈] and the resulting boronate crosslinked micelles (BCM) triggered by mannitol and/or acidic pH values .

Fig. 5

Molecular representation of monomer and the corresponding supramolecular polymer formed after their aggregation through specific interactions .

Fig. 6

Schematic illustration of enhanced permeation and retention (EPR) effect.

Fig. 7

Differently shaped NPs: sphere, rod, cube and disk. The top shows the transmission electron microscopy images of these NPs. The bottom shows the PEGylated NPs with grafting density 1.6 chains per nm² in molecular simulations .

Fig. 8

A multiscale-modeling framework for drug delivery processes. Reorganized with permission from .