Dual enzyme responsive microcapsules simulating an “OR” logic gate for biologically triggered drug delivery applications

Abstract

Hollow microcapsules capable of disintegrating in response to dual biological stimuli have been synthesized from two FDA approved drug molecules. The capsules fabricated from protamine and chondroitin sulphate disintegrate in the presence of either trypsin or hyaluronidase enzymes, which are documented to be simultaneously over-expressed under some pathological conditions.

Fabrication of Electrochemical-Based Bioelectronic Device and Biosensor Composed of Biomaterial-Nanomaterial Hybrid

“…Besides these logic gates, enzyme-based logic gates using interfacial pH change (Pita et al 2009a), enzyme-functionalized nanoparticles (Pita et al 2008) and supramolecular enzymehydrogel hybrids (Ikeda et al 2014) were developed. These enzyme-based logic gates offer a huge potential for application in wide areas including clinical field for drug delivery and physiological conditioning assessment (Mailloux et al 2014;Pita et al 2009b;Radhakrishnan et al 2013).…”

“…There is also the case of programmable DNA-enzyme conjugates fabrication for logic gate (Gianneschi and Ghadiri 2007). These biomolecular logic gates give a chance to develop the effective complex computing functions demonstration for biocomputer system development (Ogihara and Ray 2000), also enrich the life of mankind due to the expanded application of biomolecules in clinical field (Mailloux et al 2014;Pita et al 2009b;Radhakrishnan et al 2013).…”

Coupling of Biomolecular Logic Gates with Electronic Transducers: From Single Enzyme Logic Gates to Sense/Act/Treat Chips

“…One of the most promising areas for biomolecular logic gates and systems is their application in the logically triggered activation of actuator devices. Coupling of logic output with actuators, capable for release and/or delivery of therapeutic agents (drugs), might lead to intelligent sense/act and sense/act/treat theranostic (therapeutic and diagnostic) devices [8,[45][46][47][48]. Recently, we proposed a challenging concept based on the on-chip integration of biomolecular gates with a biosensor/actuator system -a so-called biomolecular logic chip (BioLogicChip) [22]: The BioLogicChip will be capable of detecting multiple analytes (e. g., a panel of biomarkers) and subsequently convert them into electrical output signals in accordance to defining specific combinations of logic "0" and "1", which are characteristic for particular diseases.…”

“…These molecular logic elements might even enable gate-to-gate communication with the possibility of addressing and switching between "on" and 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 "off" states. Moreover, interfacing of biomolecular logic systems with electronic transducers and stimuli-responsive materials may result in novel digital biosensors and actuators [8,16], logically triggered drug-release systems [12,[17][18][19][20], and closed-loop intelligent sense/act/treat biochips [21,22]. Such biochips are considered as highly attractive for personalized medicine and theranostics.…”

Concept for a biomolecular logic chip with an integrated sensor and actuator function

“…In addition, a multi‐enzyme logic‐gate network has been developed to assess the traumatic brain injury and soft tissue injury . Moreover, biomolecular logic principles have been utilized for the development of a “Sense‐and‐Act” system for biologically triggered drug release application .…”