Nanoscale bioconjugates: A review of the structural attributes of drug-loaded nanocarrier conjugates for selective cancer therapy

Abstract

Nanobioconjugates are nanoscale drug delivery vehicles that have been conjugated to or decorated with biologically active targeting ligands. These targeting ligands can be antibodies, peptides, aptamers, or small molecules such as vitamins or hormones. Most research studies in this field have been devoted to targeting cancer. Moreover, the nanostructures can be designed with an additional level of targeting by being designed to be stimulus-responsive or "smart" by a judicious choice of materials to be incorporated into the hybrid nanostructures. This stimulus could be an acidic pH, raised temperature, enzyme, ultrasound, redox potential, an externally applied magnetic field, or laser irradiation. In this case, the smart capability can increase the accumulation at the tumor site or the on-demand drug release, while the ligand ensures selective binding to the tumor cells. The present review highlights some interesting studies classified according to the nanostructure material. These materials include natural substances (polysaccharides), multi-walled carbon nanotubes (and halloysite nanotubes), metal-organic frameworks and covalent-organic frameworks, metal nanoparticles (gold and silver), and polymeric micelles.

Keywords: Biotechnology; High-tech nanostructures; Ligands for molecular recognition; Nanotechnology; Synergistic therapeutic effects; Targeted cancer therapy.

Graphical abstract

Figure 1

a) H₂O₂-triggered release procedure of HNTs@PVA@PA. Figure a was adapted by permission from: Chemical Engineering Journal, 2020, 380, 122474 [94]. b) The illustration of the ultrasound-responsive drug release using a vibration enhancer. (i) Hydrogel microbeads contained vibration enhancers and drug models. (ii) Vibration enhancers in the hydrogel microbeads under the applied ultrasound irradiation. (iii) Drug models were released from hydrogel microbeads by the vibration of hydrogel microbeads and vibration enhancers. Figure c was adapted by permission from: Materials & Design, 2021, 203, 109580 [99].

Figure 2

The sketch of the shape and morphology of some of the drug nanocarriers and the conjugated biological sections, utilized by the researchers in the last decade. Photothermal therapy (PTT) defines as a cancer treatment approach using electromagnetic irradiation. The conjugation of nanomaterials with biological sections (aptamers, antibodies, CPP, FA) creates various nanocarriers for drug loading and transferring the cargo to the target cells.

Figure 3

The chemical structures of a) carrageenan. Figure a was adapted by permission from: Marine Drugs, 2020, 18, 658 [137], b) dextran, c) chitosan, d) hyaluronic acid. Figures b–d was adapted by permission from: International Journal of Molecular Sciences, 2020, 21, 9159 [138].

Figure 4

a) The schematic illustration of the receptor-mediated endocytosis (RME) for drug conjugate, drug release process, and drug attachment to the target protein. Figure a was adapted by permission from: Bioconjugate chemistry, 2010, 21, 979–987 [148]. b) The schematic illustration of the suggested hypothesis of utilizing AS1411 derivatives for carrying C8 ligand into nucleolin-overexpressed cancer cells. Figure b was adapted by permission from: Scientific reports, 2019, 9, 1–12 [154]. c) The schematic illustration of the internalization of GEM-conjugated polyamino acid-based micelles and their reduction-responsive drug release. Figure c was adapted by permission from: Polymer Chemistry, 2017, 8, 2490–2498 [157]. d) The schematic illustration of the structure and suggested mechanism for the targeted impact of CSKSSDYQC-dextran-poly (lactic-co-glycolic acid) nanoparticles (CSK-DEX-PLGA-NPs = CDPs). Figure d was adapted by permission from: Molecular Pharmaceutics, 2019, 16, 518–532 [158].

Figure 5

a) Preparation route of Pab-functionalized MWCNTs. (DSPE-PEG: Distearoyl-sn-glycero-3- phosphoethanolamine conjugated to polyethylene glycol5000 terminated with a methoxy group, Mal: maleimide, FITC: fluorescein isothiocyanate). This figure was adapted by permission from: ACS applied materials & interfaces, 2018, 10, 33464–33473 [172]. b) A schematic of the preparation strategy of cRGD-functionalized polylipopeptide micelles (cRGD-Lipep-Ms). (PEG-PAPA: poly(ethylene glycol)-b-poly(α-aminopalmitic acid), MMAE: Monomethyl auristatin E, cRGD: cyclic RGD (arginine–glycine–aspartic) peptides, cRGD-Lipep-Ms: cRGD-functionalized polylipopeptide micelles). This figure was adapted by permission from: Molecular Pharmaceutics, 2018, 15, 4854–4861 [173]. c) The illustration of MWCNT/γ-Fe₂O₃/PEI-PEG-FA/DOX synthesis. This figure was adapted by permission from: Journal of Biotechnology, 2021, 341, 51–62 [174].

Figure 6

(a) MTT test using a docetaxel-containing iron oxide/AuNPs nanocarrier on the MCF-7 breast cancer cell line (C: MCF-7 control, DXL: individual docetaxel, P4: mercaptopropyl-modified Fe₃O₄/PVA particles, P6: Fe₃O₄/PVA-10%DXL, and P7: Au/Fe₃O₄/PVA-10%DXL), (b) the ex vivo fluorescence images after the major organs were excised and tetramethylindocarbocyanine iodide (DiR) fluorescence distribution was studied using a Maestro in vivo imaging system, and (c) a schematic presentation of the LSPR heating by AuNPs agglomerated in the magnetically delivered Au/Fe₃O₄/PVA-10%DXL nanomedicine composite. This figure was adapted by permission from: Small, 2020, 16, 2002733 [102].