Choice of Nanoparticles for Theranostics Engineering: Surface Coating to Nanovalves Approach

Abstract

Surface engineered nanoparticles (metallic and nonmetallic) have gained tremendous attention for precise imaging and therapeutics of cell/tumors at molecular and anatomic levels. These tiny agents have shown their specific physicochemical properties for early-stage disease diagnosis and cancer theranostics applications (imaging and therapeutics by a single system). For example, gold nanorods (AuNRs) demonstrate better photothermal response and radiodensity for theranostics applications. However, upon near infrared light exposure these AuNRs lose their optical property which is characteristic of phototherapy of cancer. To overcome this issue, silica coating is a safe choice for nanorods which not only stabilizes them but also provides extra space for cargo loading and makes them multifunctional in cancer theranostics applications. On the other hand, various small molecules have been coated on the surface of nanoparticles (organic, inorganic, and biological) which improve their biocompatibility, blood circulation time, specific biodistribution and tumor binding ability. A few of them have been reached in clinical trials, but, struggling with FDA approval due to engineering and biological barriers. Moreover, nanoparticles also face various challenges of reliability, reproducibility, degradation, tumor entry and exit in translational research. On the other hand, cargo carrier nanoparticles have been facing critical issues of premature leakage of loaded cargo either anticancer drug or imaging probes. Hence, various gate keepers (quantum dots to supramolecules) known nanovalves have been engineered on the pore opening of the cargo systems. Here, a review on the evolution of nanoparticles and their choice for diagnostics and therapeutics applications has been discussed. In this context, basic requirements of multifunctional theranostics design for targeted imaging and therapy have been highlighted and with several challenges. Major hurdles experienced in the surface engineering routes (coating to nanovalves approach) and limitations of the designed theranostics such as poor biocompatibility, low photostability, non-specific targeting, low cargo capacity, poor biodegradation and lower theranostics efficiency are discussed in-depth. The current scenario of theranostics systems and their multifunctional applications have been presented in this article.

Figure 1

Representative nanoparticles based targeted theranostics design.

Figure 2

(a) Schematic of surface engineered nanotheranostics, (b) Spin-spin relaxation rate, (c) fluorescence (FL) spectra of ICG dye tagged engineered nanotheranostics, (d) in vitro cancer cell imaging and therapeutics and (e) in vivo tumor imaging followed by multimode imaging modalities. Reproduced with permission from Acc. Chem. Res., 2011, 44, 936 published by American Chemical Society.

Figure 3

Schematics of surface engineered nanotheranostics. (Top) surface covering/coating of nanoparticles viz., liposomal surface covering with gold nanorods and graphene oxide, gold nanorods surface coating with silica shell, reproduced with permission from Bioconjugate Chem. 2018, 29, 5, 1510, Bioconjugate Chem. 2018, 29, 12, 4012, ACS Appl. Bio Mater. 2019, 2, 8, 3312 published by American Chemical Society. (Bottom) mesoporous silica nanoparticles and their pores are valved/or gated with nanodots of carbon reproduced with permission from ACS Appl. Bio Mater. 2021, 4, 2, 1693 published by American Chemical Society, Nanoscale, 2016, 8, 4537 published by Royal Society of Chemistry and J. Phys. Chem. C 2011, 115, 40, 19496 published by American Chemical Society.

Figure 4

(a) Design of surface coated multifunctional mesoporous porous system and their (b) microscopic image and (c) HeLa cancer cell imaging, surface area isotherm and pore size distribution (inset) and time dependent fluorescent cargo release performance of conjugated silica-based nanoparticles. Reproduced with permission from ACS Nano 2009, 3, 1, 197 and ACS Nano 2021, 15, 4450 published by American Chemical Society.

Figure 5

(a) Schematics of silica coated gold nanoparticles as surface engineered nanotheranostics, (b) uptake of nanotheranostics in solid tumor environment, (c, d) microscopic image of the designed nanotheranostics and their in vitro radiocontrast performance, (e, f) silica coated gold nanorods theranostics agents for targeted tumor imaging and bio-distribution, (g, h) novel engineering of liposomal surface with red emissive graphene oxide flakes and their microscopic image, (i) in vivo photo transduction response under near infrared light exposure at various time points, (j) photo triggered drug delivery response of doxorubicin loaded graphene oxide-liposomal theranostics platform and (k-n) in vitro and in vivo targeted cells/tumor imaging and distribution using red emissive graphene oxide flakes coated liposomal theranostics system, (o-r) near infrared light mediated solid tumor ablation followed by chemo-photothermal therapy and compared with standalone chemotherapy using folic acid attached red emissive graphene oxide flakes coated liposomal theranostics system and (s,t) representation of a novel engineering of gold nanorods supported liposomal theranostics system, schematic and microscopic image. Reproduced with permission from ACS Appl. Bio Mater. 2019, 2, 8, 3312, Bioconjugate Chem. 2018, 29, 12, 4012 and Bioconjugate Chem. 2018, 29, 5, 1510 published by American Chemical Society.

Figure 6

Schematic illustration of nanovalve-gated multifunctional mesoporous silica theranostics systems for loading and release of Hoechst 33342 molecules. (a,b) loading of Hoechst 33342, (c) zoomed particle's surface before capping and washing, (d) loaded Hoechst 33342 molecules in pores after capping and washing, (e) release of Hoechst 33342 molecules from the pores, (g-i) loading of dye molecules in different pore sizes of the nanoparticles and (h) chemistry of Hoechst 33342 molecule adsorbed on the silica surface. Reproduced with permission from J. Phys. Chem. C 2011, 115, 19496 published by American Chemical Society.

Figure 7

(a) Schematic representation of nanoceria capped drug loaded mesoporous silica for pH-triggered release with microscopic and elemental understanding. Reproduced with permission from ACS Appl. Mater. Interfaces 2019, 11, 1, 288 published by American Chemical Society.

Figure 8

Schematic illustration of stimuli responsive nanovalve-gates on mesoporous silica nanoparticles. (a-c) cyclodextrin gated mesoporous silica surface and their cargo release pattern reproduced with permission from ACS Nano 2015, 9, 11, 10778 published by American Chemical Society, (d-g) cross-linked network on mesoporous silica nanoparticles and molecular design of sodium alginate (SA) along with release kinetics and microscopic images, reproduced from Front. Chem. 7:59. doi: 10.3389/fchem.2019.00059 an open-access article under the terms of the Creative Commons Attribution License (CC BY), (h-j) nanopiston mechanism of phosphonate covered mesoporous silica through acid-cleavable acetal bond, reproduced with permission from J. Am. Chem. Soc. 2010, 132, 37, 13016 published by American Chemical Society.

Figure 9

(a-e) Schematic illustration of operation of nanovalves gating the pore openings on silica particles in various stimuli conditions reproduced with permission from Theranostics 2019, 9, 3341, doi: 10.7150/thno.34576 open access article under the terms of the Creative Commons Attribution (CC BY-NC) license published by IVYSPRING.