Engineering nano-drug biointerface to overcome biological barriers toward precision drug delivery

Abstract

The rapid advancement of nanomedicine and nanoparticle (NP) materials presents novel solutions potentially capable of revolutionizing health care by improving efficacy, bioavailability, drug targeting, and safety. NPs are intriguing when considering medical applications because of their essential and unique qualities, including a significantly higher surface to mass ratio, quantum properties, and the potential to adsorb and transport drugs and other compounds. However, NPs must overcome or navigate several biological barriers of the human body to successfully deliver drugs at precise locations. Engineering the drug carrier biointerface can help overcome the main biological barriers and optimize the drug delivery in a more personalized manner. This review discusses the significant heterogeneous biological delivery barriers and how biointerface engineering can promote drug carriers to prevail over hurdles and navigate in a more personalized manner, thus ushering in the era of Precision Medicine. We also summarize the nanomedicines' current advantages and disadvantages in drug administration, from natural/synthetic sources to clinical applications. Additionally, we explore the innovative NP designs used in both non-personalized and customized applications as well as how they can attain a precise therapeutic strategy.

Keywords: Biological barriers; Drug delivery; Nanomedicine; Nanoparticle.

Fig. 1

The diverse types of nanoparticles. Nanoparticles (NPs) could be classified into four main categories according to size, shape, and physicochemical properties. Each class of NPs includes several subclasses, some of which are highlighted here. Each class has numerous advantages and disadvantages regarding conveyed cargo, delivery, and patient responses

Fig. 2

Illustration of various strategies used to develop smart nanoparticles for precision drug delivery. Material and surface properties, architecture, and targeting responsiveness are characteristics of nanoparticles (NPs) that could be intelligently modified to customize the platform for a particular application. Altogether combinations of these characteristics result in an almost infinite number of NPs features and platforms

Fig. 3

Highlighting some of the sequential biological barriers that nanoparticles (NPs) must overcome to achieve precision drug delivery. As discussed in this review, smarter NP designs that optimize delivery can significantly improve the effectiveness of precision medicines, hence expediting their clinical translation

Fig. 4

PEG surface modification enhances the ability of BPQDs to penetrate the sputum layer. A Visual inspection of how various samples penetrate through the artificial mucus layers. B Absorbance (at 595 nm) detection at the bottom layer agarose gel of sputum layer penetration by diverse nanoparticles two h after administration. CS chitosan, AM amikacin, BPQDs black phosphorus quantum dots. Reproduced with permission from Ref. [85] Copyright 2020, John Wiley and Sons

Fig. 5

Effect of cell age and sex on uptake of nanoparticles. A Fluorescence micrographs of NP colocalization in lysosomes of young IMR90 and senescent IMR90 cells. Experiments were conducted at 37 °C for 2 h. Lysosomes were stained with LysoTracker Blue fluorescent dye (blue) and quantum dots (QD)/QD-HC red marked nanoparticles. Bar = 50 μm. Reproduced with permission from Ref. [168] Copyright 2019, American Chemical Society. B Immunohistochemical imaging of female and male human amniotic stem cells (hAMSCs) demonstrated a significant increase in QD uptake in female vs male cells. The scale bar represents 50 μm in all panels. (C) QD uptake was quantified using confocal images (n = 7/group). Reproduced with permission from Ref. [169] Copyright 2018, American Chemical Society

Fig. 6

The general scheme of bioconjugation reactions for the synthesis of drug-loaded nanobiohybrid carriers. Step A: NPs are first functionalized with a chemical partner and then loaded with the therapeutic agent of choice. Step B: The chemical group is also incorporated into the surface of bacteria. Step C: Bioconjugation reaction between the chemical partners leads to the bioconjugate bacteria-nanomaterial

Fig. 7

Strategies for carrier-free nanodrugs to improve drug delivery and stability. A A bioinspired coating offers a novel method to successfully inhibit and delay the Ostwald ripening of hydrophobic drug nanoparticles, resulting in smaller and evenly sized particles that provide enhanced drug delivery and long-term colloidal stability. Reproduced with permission from Ref. [221] Copyright 2016, American Chemical Society. B A novel strategy to prepare lollipop-like dual-drug-loaded nanoparticles, Polydopamine (PDA), fills the gaps between the doxorubicin (DOX) and gossypol molecules to form the super-compact long-circulating nanoparticles and enhanced tumor penetration. Reproduced with permission from Ref. [222] Copyright 2019, John Wiley and Sons