Exploring the Potential of Zein Nanoparticles in Personalised Cancer Therapy, Highlighting Their Various Methodologies, Applications and Challenges

Abstract

Zein, a corn-derived prolamine protein, has become a powerful ally in the fight against cancer, particularly non-small cell lung cancer (NSCLC.) Its unique attributes, enriched by modifiable hydroxyl and amino groups, have led to the development of advanced functionalised drug delivery systems. Innovative techniques like chemical crosslinking, desolvation, dispersion and micromixing have led to the creation of zein-based nanoparticles, revolutionising cancer therapy. Central to this examination is the remarkable ability of zein NPs to enhance drug stability, optimise oral bioavailability and improve targeted drug delivery, specifically tailored to combat NSCLC. This represents not just a technological breakthrough but a paradigm shift, ushering in a new era of precise, personalised and effective cancer treatment. Zein, a hydrophobic nanoparticle, is a promising drug for cancer treatment. However, its journey to the clinic is challenging due to its hydrophobic nature and the need for advanced evaluative platforms. This review emphasises the need for rigorous research to align zein's potential with real-world applications. It offers a synthesis of methodologies, applications, and obstacles, aiming to see zein nanoparticles as a central element in cancer therapy innovations. The review encourages researchers, clinicians and industry professionals to embrace the potential of zein and promote the convergence of laboratory innovation and clinical application.

Keywords: advanced drug delivery mechanisms; cancer therapy; oral bioavailability; precision medicine; zein nanoparticles.

FIGURE 1

Routes of administration for zein carriers and key properties of zein relevant to each administration route [Adapted from reference: [36]].

FIGURE 2

Preparation of zein nanoparticles: (A) antisolvent precipitation/liquid–liquid dispersion/phase separation techniques and (B) electrohydrodynamic atomisation [Adapted from reference: [44]].

FIGURE 3

(i) The methods of preparation of zein/polysaccharide nanoparticles: (A) pH‐ and heat‐induced antisolvent precipitation; (B) antisolvent coprecipitation [Adapted from reference [45]]; (ii) The morphological observation of nanoparticles by (A) AFM, (B) TEM and (C) SEM. [Adapted from reference [46]].

FIGURE 4

SEM images of (A) zein nanoparticles and (B) zein/PGA nanoparticles. [Reprinted from [47]].

FIGURE 5

Properties of zein nanoparticles making them suitable for targeted delivery of chemotherapeutic agents against a wide range of cancers.

FIGURE 6

(i) (A) An illustration depicting the environmentally friendly synthesis process and subsequent utilisation of AuZNS (gold‐coated zein nanoshells) for imaging‐guided plasmonic photothermal therapy. The associated micrographic images present the size distribution of the synthesised AuZNS, and Zeta potential measurements are included to characterise their surface charge; (B) Elemental analysis results demonstrate the elemental composition of AuZNS, and the absorbance spectrum highlights their optical properties. Moreover, the photothermal transduction capability of AuZNS is illustrated; (C) biocompatibility and hemolysis studies are showcased to assess the safety of AuZNS. X‐ray images of negative controls, AuZNS samples and Omnipaque (a contrast agent) are displayed at varying concentrations, offering a comparison of their imaging properties; (D) Qualitative analysis is presented, focusing on non‐targeted photothermal therapy conducted on C33A cells using propidium iodide staining. The uptake study examines the cellular internalisation of AuZNS, distinguishing between targeted and non‐targeted photothermal therapy approaches. Statistical significance is denoted by asterisks, with ‘**p < 0.01’ and ‘****p < 0.0001’ indicating the levels of statistical significance. [This figure and associated data are adapted with permission from a study titled ‘Facile synthesis of plasmonic zein nanoshells for imaging‐guided photothermal cancer therapy’ by Chauhan DS et al., published in the journal ‘Materials Science and Engineering C: Materials for Biological Applications’ in 2018 and copyrighted by Elsevier [59]]. (ii) (A) Schematic diagram of the ‘all‐in‐one’ and ‘one‐for‐all’ nanoplatform for combined ‘chemo−immuno−photothermal’ therapy. (B) Fabrication and characterisation of DTX‐loaded zein/CSP‐GTP/Fe (III) NPs and the in vitro drug release. (C) In vivo therapeutic efficacy of various treatments on 4T1 tumour‐bearing mice. *p < 0.05; **p < 0.01; ***p < 0.001 compared to control. #, p < 0.05; ##, p < 0.01; ###, p < 0.001. [Reprinted with permission from [60]].

FIGURE 7

(I) (a) Illustration of the face‐centred cubic arrangement of O²⁻ anions and location of ferric and ferrous ions in octahedral and tetrahedral sites; (b) illustration of the ferrimagnetic network formed by ferrous and ferric ions in magnetite; (c) illustration of domain formation in ferrimagnetic material and resulting magnetisation behaviour; (d) illustration of a single‐domain nanoparticle and resulting superparamagnetic curve [94]; (II) Examples of particle morphologies: (A) nanospheres; (B) plates; (C) tetrahedrons; (D) cubes; (E) truncated octahedrons; (F) octahedrons; (G) concaves; (H) octapods; (I) multibranches. Reprinted from [95]; (III) (a) Anchoring groups grafted on an iron oxide surface, from left to right, dopamine, siloxane, hydroxyamate, 2,3‐dihydroxybenzamide, mono‐ and bis‐phosphonate, and carboxylate; (b) examples of capping agents providing electrostatic stabilisation; (c) polymer coatings providing steric stabilisation [94]; (IV) Binary categorisation of proinflammatory (M1‐like) and anti‐inflammatory (M2‐like) macrophages in the tumour microenvironment. Reprinted from [96]; (V) Illustration of (A) SPION‐based RNAi platforms (AIO: Amorphous iron oxide) and (B) their interaction with tumour cells. Upon i.v. administration, nanoparticles accumulate in tumour cells through the EPR effect. Internalisation of the nanoparticles within the endosome and subsequent release of iron ions leads to osmotic pressure and/or endosomal membrane oxidation. The resulting endosomal escape induces the release of RNAi and iron ions, resulting in MCT4 silencing and oxidative stress via the Fenton‐like reaction. Reprinted from [97].