Design, Synthesis and Architectures of Hybrid Nanomaterials for Therapy and Diagnosis Applications

Abstract

Hybrid nanomaterials based on inorganic nanoparticles and polymers are highly interesting structures since they combine synergistically the advantageous physical-chemical properties of both inorganic and polymeric components, providing superior functionality to the final material. These unique properties motivate the intensive study of these materials from a multidisciplinary view with the aim of finding novel applications in technological and biomedical fields. Choosing a specific synthetic methodology that allows for control over the surface composition and its architecture, enables not only the examination of the structure/property relationships, but, more importantly, the design of more efficient nanodevices for therapy and diagnosis in nanomedicine. The current review categorizes hybrid nanomaterials into three types of architectures: core-brush, hybrid nanogels, and core-shell. We focus on the analysis of the synthetic approaches that lead to the formation of each type of architecture. Furthermore, most recent advances in therapy and diagnosis applications and some inherent challenges of these materials are herein reviewed.

Keywords: hybrid nanomaterials; inorganic-polymeric; nano-architectures.

Figure 1

Strategies of polymer grafting: (a) grafting to, (b) grafting from and (c) grafting through.

Figure 2

Different architectures of hybrid nanomaterials: (a) core-brush, (b) hybrid nanogel, and (c) core-shell.

Figure 3

Scheme of atom transfer radical polymerization (ATRP) equilibrium. Reprinted with permission from ref. [56]. © 2012, Wiley Online Library.

Figure 4

Scheme of SPION-PNIPAM nanoparticles by ATRP. Reprinted with permission from ref. [80]. © 2018, Royal Society of Chemistry.

Figure 5

Scheme of the synthesis of SiO₂NPs@poly(NIPAM-co-GMA)@APBA particles by combining SI-ATRP with the CuAAC “click” reaction. Reprinted with permission from ref. [70].

Figure 6

Scheme of the synthetic route of well-dispersed bifunctional nanoparticles (FITC-MNPs). Reprinted with permission from ref. [68]. © 2012, Royal Society of Chemistry.

Figure 7

Mechanism of reversible addition–fragmentation chain Transfer (RAFT) polymerization. Reprinted with permission from ref. [84]. © 2015, American Chemical Society.

Figure 8

Synthetic route of thermo-responsive Fe₃O₄@SiO₂NPs. Reprinted with permission from ref. [88]. © 2011, Royal Society of Chemistry.

Figure 9

(a) Reaction steps for the preparation of functionalized-MNPs. (b) Structure of Tiiii receptors, phosphonic acid grafting agent, and the drugs used in their complexed Reprinted with permission from ref. [114]. © 2013, Royal Society of Chemistry.

Figure 10

Synthesis and post-modification of polymer-coated MNPs. Reprinted with permission from ref. [119]. © 2015, American Chemical Society.

Figure 11

Scheme of physical (a) and covalent (b) hybrid nanogels.

Figure 12

Synthetic approach for obtaining Cy5.5-Lf-MPNA nanogels (NGs). Reprinted with permission from ref. [150]. © 2013, Elsevier.

Figure 13

Schematic representation of thermo-responsive NGs loaded with maghemite. Reprinted with permission from ref. [155]. © 2017, American Chemical Society.

Figure 14

Development of the doxorubicin (DOX)-loaded hollow hybrid NGs serving as a multifunctional anticancer theranostic platform. Reprinted with permission from ref. [156].

Figure 15

(1) Surface functionalization of the Fe₂O₃NPs with silane agents and boronic acid derivatives. (2) thermally-induced micelle formation and hydrophobic drug loading (a); crosslinking of the poly(vinyl alcohol) with the functionalized Fe₂O₃NPs (b); formation of drug-loaded NGs after cooling down below the LCST (c) and glucose-pH-triggered release of the drug molecules (d). Reprinted with permission from ref. [144]. © 2014, Royal Society of Chemistry.

Figure 16

Schematic illustration of magnetic core−shell DNA microgels. Reprinted with permission from ref. [177]. © 2014, Royal Society of Chemistry.

Figure 17

Schematic illustration to highlight the importance of understanding the structure/property relationship of the different systems to achieve successful in vitro and in vivo applications.