Impact of nanoparticles on amyloid β-induced Alzheimer's disease, tuberculosis, leprosy and cancer: a systematic review

Abstract

Nanotechnology is an interdisciplinary domain of science, technology and engineering that deals with nano-sized materials/particles. Usually, the size of nanoparticles lies between 1 and 100 nm. Due to their small size and large surface area-to-volume ratio, nanoparticles exhibit high reactivity, greater stability and adsorption capacity. These important physicochemical properties attract scientific community to utilize them in biomedical field. Various types of nanoparticles (inorganic and organic) have broad applications in medical field ranging from imaging to gene therapy. These are also effective drug carriers. In recent times, nanoparticles are utilized to circumvent different treatment limitations. For example, the ability of nanoparticles to cross the blood-brain barrier and having a certain degree of specificity towards amyloid deposits makes themselves important candidates for the treatment of Alzheimer's disease. Furthermore, nanotechnology has been used extensively to overcome several pertinent issues like drug-resistance phenomenon, side effects of conventional drugs and targeted drug delivery issue in leprosy, tuberculosis and cancer. Thus, in this review, the application of different nanoparticles for the treatment of these four important diseases (Alzheimer's disease, tuberculosis, leprosy and cancer) as well as for the effective delivery of drugs used in these diseases has been presented systematically. Although nanoformulations have many advantages over traditional therapeutics for treating these diseases, nanotoxicity is a major concern that has been discussed subsequently. Lastly, we have presented the promising future prospective of nanoparticles as alternative therapeutics. In that section, we have discussed about the futuristic approach(es) that could provide promising candidate(s) for the treatment of these four diseases.

Keywords: Alzheimer's disease; Cancer; Drug delivery; Leprosy; Nanoparticles; Tuberculosis.

Figure 1. Schematic illustration of anti-amyloidogenic and cytoprotective effects exerted by metallic/inorganic, polymeric and self-assembled nanoparticles against in vitro and in vivo Aβ fibrillation process

Both inorganic and polymeric nanoparticles share almost similar mode of action to ameliorate Aβ induced toxicity by binding to different intermediates (i.e. the different forms of Aβ species found during the fibrillation process such as monomeric species, oligomeric species etc.) of fibrillation process and by neutralizing their toxic effects. The plot of “Fibrils vs Incubation Time” has been reprinted (adopted) with permission from “Peptide and Protein Mimetics Inhibiting Amyloid β-Peptide Aggregation, Takahashi T, Mihara H., Acc Chem Res. 2008, 41(10),:1309–1318. doi: 10.1021/ar8000475. Copyright (2008) American Chemical Society”.

Figure 2. Impact of various metallic nanoparticles in tuberculosis

Consolidated elucidation of various effects of cell penetrable bare/capped monometallic (AgNPs, AuNPs, citrate capped AuNPs, PAH capped AuNPs, ALG capped AgNPs, PVP capped AgNPs etc.) and bimetallic nanoparticles (Ag-AuNPs) on Mycobacterium tuberculosis pathogen. ALG, alginate; INH, isoniazid; PAH, polyallylamine hydrochloride; PVP, polyvinylpyrrolidone; RF, rifampicin; MSNs-AgBrNPs and Ag@MSNs, silver-containing mesoporous silica-based nanosystems. Image of MSNs-AgBrNPs and Ag@MSNs have been redrawn (adopted) from “Mesoporous silica nanoparticles containing silver as novel antimycobacterial agents against Mycobacterium tuberculosis, 197, Montalvo-Quirós S, Gómez-Graña S, Vallet-Regí M, Prados-Rosales RC, González B and Luque-Garcia JL, 111405, Copyright (2021) with permission from Elsevier”.

Figure 3. Effect of citrate capped gold and silver nanoparticles (AuNPs and AgNPs) on the structure and chaperone function of M. leprae HSP18

Schematic representation of the differential effect of these two nanoparticles on the structure and chaperone function of HSP18 (which plays an important role in the growth and survival of M. leprae pathogen inside hosts).

Figure 4. Application of nanotechnology in cancer

Schematic depiction of the potential of HSP90 inhibitor/HSP70 inhibitor based nanoformulations towards the treatment of different types of cancer; 17-AAG, 17-allylaminogeldanamycin; 6BrCaQ, N-(6-bromo-1-methyl-2-oxoquinolin-3-yl)-4-methoxybenzamide; 17-DMAG, 17-(2-dimethylaminoethyl)amino-17-demethoxygeldanamycin; PES, 2-phenylethynesulfonamide; SNX-2112, 4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-5,7-dihydroindazol-1-yl]-2-[(4-hydroxycyclohexyl)amino]benzamide; VER-155008, 5′-O-[(4-Cyanophenyl)methyl]-8-[[(3,4-dichlorophenyl)methyl]amino]-adenosine.