An enzyme-controlled mesoporous nanomachine for triple-responsive delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Enzyme Engineering

Background:

• Developing targeted drug delivery systems is crucial for improving therapeutic efficacy and reducing side effects.
• Enzyme-responsive nanomaterials offer precise control over drug release based on biological cues.
• Mesoporous silica nanoparticles (MSNs) are versatile platforms for drug encapsulation and controlled release.

Purpose of the Study:

• To construct a novel enzyme-controlled nanomachine with multiple release mechanisms.
• To investigate the triggered release of encapsulated payloads using specific chemical and biological signals.
• To evaluate the efficacy of the nanodevice for targeted drug delivery in cancer cells.

Main Methods:

• Assembly of a nanodevice using mesoporous silica nanoparticles modified with specific moieties and capped with a neoglycoenzyme.
• Utilizing β-cyclodextrin-modified glucose oxidase for enzyme-controlled payload release.
• Investigating release mechanisms triggered by hydrogen peroxide (H2O2), acidic conditions, and glucose.
• Employing doxorubicin as a model drug for release studies in HeLa cancer cells.

Main Results:

• The nanodevice demonstrated triggered release of encapsulated payload in the presence of H2O2 and acidic media.
• Glucose acted as an input signal, initiating cargo release via enzymatic production of gluconic acid and H2O2.
• The enzymatic activity successfully disrupted the mesoporous silica nanoparticle gating mechanism.
• Successful enzyme-controlled release of doxorubicin was achieved in HeLa cancer cells.

Conclusions:

• A novel enzyme-controlled nanomachine with multiple, on-demand release mechanisms was successfully constructed.
• The nanodevice utilizes a combination of chemical and enzyme-triggered responses for precise cargo delivery.
• This platform shows significant potential for targeted cancer therapy and advanced drug delivery applications.