Nanoscale coatings for encapsulation of biological entities

Abstract

Methods, systems, and devices are disclosed for encapsulating biological entities with preservation of their biological activity. In one aspect, a method of encapsulating a biological entity includes templating a biocompatible material onto a biological structure to form a coating structure enclosing the biological structure, the coating structure having a size in the nanometer range, in which the coated biological structure preserves its biological activity within the coating structure. In some implementations of the method, the biological structure includes a virus and the biocompatible material includes silica.

What is claimed is: 
     
         1 . A method to produce a bioactive payload delivery device, comprising:
 forming an intermediate structure by binding a polymer material with a biological substance based on an electrostatic force, wherein the formed intermediate structure includes a plurality of regions presenting a net surface charge; and   forming a coating structure of a biocompatible material directly on the formed intermediate structure to enclose the biological substance,   wherein the coating structure preserves biological activity of the biological substance enclosed therein, thereby producing a bioactive payload delivery device.   
     
     
         2 . The method of  claim 1 , wherein the coating structure includes a nanoparticle sized in a nanometer regime. 
     
     
         3 . The method of  claim 1 , wherein the biological substance includes at least one of a virus, bacteria, protein, enzyme, prodrug, or nucleic acid vector including a DNA or an RNA. 
     
     
         4 . The method of  claim 1 , wherein the biocompatible material includes silica. 
     
     
         5 . The method of  claim 1 , wherein the forming the intermediate structure includes cross-reacting the biological substance with a poly-cationic polymer material to form a positively-charged surface in the plurality of regions of the intermediate structure. 
     
     
         6 . The method of  claim 5 , wherein the poly-cationic polymer material includes poly-l-lysine. 
     
     
         7 . The method of  claim 6 , wherein the forming the coating structure includes a charge-mediated silica sol-gel condensation reaction directly onto the surface of the intermediate structure, wherein the formed coating structure includes an enveloping silica matrix encapsulating the biological substance. 
     
     
         8 . The method of  claim 1 , further comprising:
 adding a sensitizing agent to produce ultrasound triggered cavitation centers inside the coating structure,   wherein the adding the sensitizing agent is implemented prior to the forming the coating structure.   
     
     
         9 . The method of  claim 8 , wherein the sensitizing agent includes a fluorocarbon nanoemulsion. 
     
     
         10 . The method of  claim 8 , further comprising delivering the biological substance to a target cell or tissue in a living organism, the delivering comprising:
 injecting the produced bioactive payload delivery device through vasculature of the body, wherein the bioactive payload delivery device extravasates from the vasculature to the target cell or tissue; and   applying acoustic energy to an area of the living organism including or proximate to the target cell or tissue to cause the sensitizing agent to rupture the coating structure and release the biological substance to the target cell or tissue.   
     
     
         11 . The method of  claim 1 , further comprising:
 adding a pharmaceutical drug or a therapeutic agent with the intermediate structure to be enclosed in the coating structure,   wherein the adding the pharmaceutical drug or the therapeutic agent is implemented prior to the forming the coating structure.   
     
     
         12 . The method of  claim 1 , further comprising:
 adding an iron oxide constituent or other nanoscale material with the biocompatible material to form the coating structure,   wherein the added iron oxide constituent or the other nanoscale material provides an agent to enhance imaging of the coating structure.   
     
     
         13 . The method of  claim 1 , wherein the coating structure stabilizes the biological substance enclosed therein, thereby allowing thermal stability at temperatures including 80° C. to −37° C. 
     
     
         14 . The method of  claim 1 , further comprising:
 lyophilizing or critical point drying the produced bioactive payload delivery device,   wherein the coating structure preserves biological activity of the biological substance enclosed within the lyophilized or critical point dried bioactive payload delivery device.   
     
     
         15 . The method of  claim 1 , further comprising:
 functionalizing an exterior surface of the coating structure.   
     
     
         16 . The method of  claim 15 , wherein the functionalizing includes adding polyethylene glycol (PEG) to provide a secondary coating capable of preventing an immune system response within a living organism in which the bioactive payload delivery device is deployed. 
     
     
         17 . The method of  claim 15 , wherein the functionalizing includes attaching a targeting ligand capable of selectively binding to a particular region of a cell or tissue of a living organism in which the bioactive payload delivery device is deployed. 
     
     
         18 . The method of  claim 15 , wherein the functionalizing includes attaching an environmental sensing moiety to the external surface, the environmental sensing moiety capable of chemically changing form based on at least one of a redox reaction, hypoxic reaction, or acidic pH in a local environment to which the bioactive payload delivery device is deployed. 
     
     
         19 . The method of  claim 1 , further comprising:
 prior to the forming the coating structure, binding a targeting moiety to the intermediate structure to enable controlled release of the biological substance from the coating structure.   
     
     
         20 . The method of  claim 19 , further comprising:
 deploying the produced bioactive payload delivery device in a fluidic media to a target substance; and   applying an external triggering signal to an area including or proximate to the target substance to cause the targeting moiety to release the biological substance from the coating structure to the target substance.   
     
     
         21 . A bioactive payload delivery device, comprising:
 an interior material structure including a polymer material and a biological substance that are bound to each other via an electrostatic interaction, wherein the interior material structure includes a plurality of regions presenting a net surface charge; and   an exterior nanostructure formed of a biocompatible material to encapsulate the interior structured material, thus preserving biological activity of the encapsulated biological substance.   
     
     
         22 . The device of  claim 21 , wherein the exterior nanostructure protects the biological substance from degradation from external environmental factors including pH, temperature, pressure, and chemical substances in an environment where the bioactive payload delivery device is deployed. 
     
     
         23 . The device of  claim 21 , wherein an outer surface of the exterior nanostructure is functionalized with a tumor targeting ligand to cause the bioactive payload delivery device to selectively accumulate in a tumor region over other tissues. 
     
     
         24 . The device of  claim 21 , wherein an outer surface of the exterior nanostructure is functionalized with an agent to increase circulation time by reducing uptake from undesired body tissues, organs, and systems, the agent including at least one of polyethylene glycol, a zwitterionic compound, or a patient-specific coating such as cell membranes. 
     
     
         25 . The device of  claim 21 , wherein the biological substance includes at least one of a virus, bacteria, protein, enzyme, prodrug, or nucleic acid vector including a DNA or an RNA. 
     
     
         26 . The device of  claim 21 , wherein the biocompatible material includes silica. 
     
     
         27 . The device of  claim 21 , further comprising:
 an acoustic sensitizing agent coupled to the interior material structure to produce ultrasound triggered cavitation centers inside the exterior nanostructure.   
     
     
         28 . The device of  claim 27 , wherein the acoustic sensitizing agent includes a fluorocarbon nanoemulsion. 
     
     
         29 . The device of  claim 27 , wherein, when deployed in a living organism, the exterior nanostructure of the device ruptures based on an applied acoustic pulse to release the biological substance within the living organism. 
     
     
         30 . The device of  claim 21 , further comprising:
 an external coating formed of polyethylene glycol (PEG) on the outer surface of the exterior nanostructure, the external coating capable of preventing an immune system response within a living organism when the device is deployed.   
     
     
         31 . The device of  claim 21 , further comprising:
 a targeting ligand formed on the outer surface of the exterior nanostructure, the targeting ligand capable of selectively binding to a particular region of a cell or tissue of a living organism when the device is deployed.   
     
     
         32 . The device of  claim 21 , further comprising:
 an environmental sensing moiety formed on the outer surface of the exterior nanostructure, the environmental sensing moiety capable of chemically changing form to release the biological substance based on at least one of a redox reaction, hypoxic reaction, or acidic pH in a local environment to which the device is deployed.   
     
     
         33 . A method for encapsulating a biological substance, comprising:
 forming a biocompatible material onto a biological structure to form a coating structure enclosing the biological structure, the coating structure having a size in the nanometer range,   wherein the biological structure preserves biological activity within the coating structure.   
     
     
         34 . The method of  claim 33 , wherein the biocompatible material includes silica. 
     
     
         35 . The method of  claim 33 , further comprising:
 forming the biological structure comprising by cross-reacting a biological substance with a poly-cationic polymer material to form a positively-charged surface in the plurality of regions of the biological structure.   
     
     
         36 . The method of  claim 35 , wherein the biological substance includes at least one of a virus, bacteria, protein, enzyme, prodrug, or nucleic acid vector including a DNA or an RNA. 
     
     
         37 . The method of  claim 35 , wherein the poly-cationic polymer material includes poly-l-lysine. 
     
     
         38 . The method of  claim 35 , wherein the forming the coating structure includes a charge-mediated silica sol-gel condensation reaction directly onto the surface of the biological structure, wherein the formed coating structure includes an enveloping silica matrix encapsulating the biological structure. 
     
     
         39 . The method of  claim 33 , further comprising:
 attaching a sensitizing agent to the biological structure, prior to the forming the biological material onto the biological structure, to produce ultrasound triggered cavitation centers inside the coating structure.   
     
     
         40 . The method of  claim 39 , wherein the sensitizing agent includes a fluorocarbon nanoemulsion.