Enzyme-polymeric/inorganic metal oxide/hybrid nanoparticle bio-conjugates in the development of therapeutic and biosensing platforms

Abstract

Background: Because enzymes can control several metabolic pathways and regulate the production of free radicals, their simultaneous use with nanoplatforms showing protective and combinational properties is of great interest in the development of therapeutic nano-based platforms. However, enzyme immobilization on nanomaterials is not straightforward due to the toxic and unpredictable properties of nanoparticles in medical practice.

Aim of review: In fact, because of the ability to load enzymes on nano-based supports and increase their renewability, scientific groups have been tempted to create potential therapeutic enzymes in this field. Therefore, this study not only pays attention to the therapeutic and diagnostic applications of diseases by enzyme-nanoparticle (NP) bio-conjugate (abbreviated as: ENB), but also considers the importance of nanoplatforms used based on their toxicity, ease of application and lack of significant adverse effects on loaded enzymes. In the following, based on the published reports, we explained that the immobilization of enzymes on polymers, inorganic metal oxide and hybrid compounds provide hopes for potential use of ENBs in medical activities. Then, the use of ENBs in bioassay activities such as paper-based or wearing biosensors and lab-on-chip/microfluidic biosensors were evaluated. Finally, this review addresses the current challenges and future perspective of ENBs in biomedical applications.

Key scientific concepts of review: This literature may provide useful information regarding the application of ENBs in biosensing and therapeutic platforms.

Keywords: Biosensing; Conjugate; Drug delivery; Enzyme Immobilization; Nanomaterial; Therapy.

Graphical abstract

Fig. 1

(A): a; Endothelial targeted antioxidant NPs formation scheme by controlled precipitation, b; Binding of Ab-PAC to cultured endothelial cells. ¹²⁵I- labeled PACs incubated with cells at 37 °C, rinsed, lysed and measured for radioactivity, c; Tissue distribution of intravenous injected PACs into mice after 30 min circulation time. Protection by endothelial-targeted catalase PACs from oxidative stress in vitro (d) and in vivo based on brochoalveolar lavage (BAL) protein (e-f) . (B): a; transmission electron micrograph of DendGDP NPs, b; Release of Dox from the NPs in the absence or presence of cathepsin (50 U), c; near-infrared fluorescence images for CT26-bearing male nude BALB/c mice. Dox itself or Dox-conjugated dendrimer NPs (5 mg/kg) were injected into the tail vein of each mouse. The major organs were removed from each mouse 48 h after injection .

Fig. 2

(A): a; Schematic representation of the glucose-sensitive insulin delivery system using glucose-sensitive BGNs, b; The glucose-sensitive insulin released from the MNs in vivo, c; Profiles of insulin release in different pH, d; SEM images of BGNs-GOx/CAT MNs, e; Profiles of blood glucose levels after Ins-BGNs-GOx/CAT MNs injection of insulin treated with diabetic rats, f; Fluorescence and bright-field histological of FITC-labeled insulin-loaded MNs attached on diabetes rats, g; Histological sections of spleen, lung, and kidney of diabetic rat after treated .

Fig. 3

A: a-b; Power outputs and polarization curves with varying concentration of glucose in artificial sweat; (a) 0.02 mg/mL (~100 µM); (b) 0.2 mg/mL (~1 mM), c; The glucose levels in sweat were monitored immediately 30 min after the beginning of the exercise . B: (a) Schematic diagram of a wireless operation of the iontophoretic-sensing tattoo device for transdermal alcohol sensing. In the diagrams of the tattoo-base device, blue and red highlights show the active zones during iontophoresis and amperometric detection, respectively, b; Control experiments without drinking, c; Experiments with consumption of 12 oz of beer measured from two different human subjects, before and after drinking alcohol beverage . C: a; Pictures demonstrating NFC between a sweat monitoring device and a smartphone to launch software for image capture and analysis, b; Results of stress distribution associated with the devices on phantom skin and respective optical images under bending with 5 cm radius, c; colorimetric detection reservoirs that enable determination of total water loss and concentrations of lactate, glucose, creatinine, pH, and chloride ions in sweat, d; images of two different types of sweat patches (small and large harvesting areas) applied to the lower back and volar forearm collected at various times during the study .