Towards feedback-controlled nanomedicines for smart, adaptive delivery

Abstract

Nanomedicines for controlled drug release provide temporal and spatial regulation of drug bioavailability in the body. The timing of drug release is usually engineered either for slow gradual release over an extended period of time or for rapid release triggered by a specific change in its physicochemical environment. However, between these two extremes, there is the desirable possibility of adaptive nanomedicines that dynamically modulate drug release in tune with its changing environment. Adaptation and response through communication with its environment is a fundamental trait of living systems; therefore, the design of biomimetic nanomedicines through the approaches of bottom-up synthetic biology provides a viable route to this goal. This could enable drug delivery systems to optimize release in synchronicity with the body's natural biological rhythms and the personalized physiological characteristics of the patient, e.g. their metabolic rate. Living systems achieve this responsiveness through feedback-controlled biochemical processes that regulate their functional outputs. Towards this goal of adaptive drug delivery systems, we review the general benefits of nanomedicine formulations, provide existing examples of experimental nanomedicines that encapsulate the metabolic function of enzymes, and give relevant examples of feedback-controlled chemical systems. These are the underpinning concepts that hold promise to be combined to form novel adaptive release systems. Furthermore, we motivate the advantages of adaptive release through chronobiological examples. By providing a brief review of these topics and an assessment of the state of the art, we aim to provide a useful resource to accelerate developments in this field. Impact statement The timing and rate of release of pharmaceuticals from advanced drug delivery systems is an important property that has received considerable attention in the scientific literature. Broadly, these mostly fall into two classes: controlled release with a prolonged release rate or triggered release where the drug is rapidly released in response to an environmental stimulus. This review aims to highlight the potential for developing adaptive release systems that more subtlety modulate the drug release profile through continuous communication with its environment facilitated through feedback control. By reviewing the key elements of this approach in one place (fundamental principles of nanomedicine, enzymatic nanoreactors for medical therapies and feedback-controlled chemical systems) and providing additional motivating case studies in the context of chronobiology, we hope to inspire innovative development of novel "chrononanomedicines."

Viewpoint: Homeostasis as Inspiration—Toward Interactive Materials

“…In this way, bending of the fins stops the reaction, allowing the structure to cool and resurrect, leading to sustained oscillations. Stimuli‐responsive hydrogels are ideal for creating chemomechanical feedback loops, as volume changes, in turn, influence mass transport and chemical reaction rates, for example, in self‐oscillating gels and rhythmic drug‐release systems . Other types of chemomechanical feedback can include self‐shadowing, as has been demonstrated for light‐responsive liquid‐crystalline elastomer thin‐films (Figure c‐ii) .…”

Nucleotide‐Selective Templated Self‐Assembly of Nanoreactors under Dissipative Conditions

“…[8] New properties are envisioned for materials, diagnostics and delivery systems able to display such kinetics. [9][10][11] Theg eneral approach to constructing chemical reaction networks involves the use of mixtures of DNA, [12] peptides, [13] enzymes [14] or entirely synthetic molecules [15] in which molecular recognition between the components directly affects the kinetic evolution of the system through allosteric effects and feedback mechanisms.Y et, in this context one element has received relatively less attention, which is the role of structure formation by the mixture of components in directing kinetic evolution of the system. [16][17][18][19][20][21][22] From this perspective,i ti si mportant to note that recently various examples of chemically fuelled transient formation of selfassembled structures have been reported.…”

Nucleotide‐Selective Templated Self‐Assembly of Nanoreactors under Dissipative Conditions

“…that cannot be observed in traditional reaction mixtures [8] . New properties are envisioned for materials, diagnostics and delivery systems able to display such kinetics [9–11] . The general approach to constructing chemical reaction networks involves the use of mixtures of DNA, [12] peptides, [13] enzymes [14] or entirely synthetic molecules [15] in which molecular recognition between the components directly affects the kinetic evolution of the system through allosteric effects and feedback mechanisms.…”

“…[8] New properties are envisioned for materials,d ia-gnostics and delivery systems able to display such kinetics. [9][10][11] Theg eneral approach to constructing chemical reaction networks involves the use of mixtures of DNA, [12] peptides, [13] enzymes [14] or entirely synthetic molecules [15] in which molecular recognition between the components directly affects the kinetic evolution of the system through allosteric effects and feedback mechanisms.Y et, in this context one element has received relatively less attention, which is the role of structure formation by the mixture of components in directing kinetic evolution of the system. [16][17][18][19][20][21][22] From this perspective,i ti si mportant to note that recently various examples of chemically fuelled transient formation of self-assembled structures have been reported.…”