Nucleic acid delivery scaffolds

Abstract

Disclosed herein, inter alia, are degradable nanoparticles, nanoarrays, and methods of use thereof in nucleic acid sequencing.

1 .- 30 . (canceled) 
     
     
         31 . A method of forming a multilayer polymer composition, said method comprising:
 contacting a solid support with a first plurality of first particles to form a first layer of first particles, wherein each first particle comprises a first degradable particle core and a first polymer shell attached to said particle core, wherein said first polymer shell comprises a first bioconjugate reactive moiety;   contacting the first layer of first particles with a first degrading agent and decomposing the first degradable particle core and forming a first polymer layer;   contacting the solid support with a second plurality of second particles to form a second layer of second particles, wherein each second particle comprises a second degradable particle core and a second polymer shell attached to said particle core, wherein said second polymer shell comprises a second bioconjugate reactive moiety; and   contacting the second with a second degrading agent and decomposing the second degradable particle core and forming a second polymer layer, thereby forming a multilayer polymer composition.   
     
     
         32 . The method of  claim 31 , wherein the first particles comprise a plurality of first bioconjugate reactive moieties and the second particles comprises a plurality of second bioconjugate reactive moieties. 
     
     
         33 . The method of  claim 31 , further comprising contacting the solid support with a first biomolecule comprising a third bioconjugate reactive moiety and attaching the first biomolecule to the first polymer shell via a bioconjugate linker formed via a reaction between the first bioconjugate reactive moiety and the third bioconjugate reactive moiety. 
     
     
         34 . The method of  claim 33 , further comprising contacting the solid support with a second biomolecule comprising a fourth bioconjugate reactive moiety and attaching the second biomolecule to the second polymer shell via a bioconjugate linker formed via a second bioconjugate reactive moiety and the fourth bioconjugate reactive moiety. 
     
     
         35 . The method of  claim 34 , wherein the first and second biomolecule independently comprise an oligonucleotide comprising two different primer sequences. 
     
     
         36 . The method of  claim 31 , wherein the first degrading agent and the second degrading agent independently comprise an acid. 
     
     
         37 . The method of  claim 31 , wherein the first degrading agent and the second degrading agent independently comprise a base. 
     
     
         38 . The method of  claim 31 , wherein the first degrading agent and second degrading agent independently comprise a pH of 8.0 or greater. 
     
     
         39 . The method of  claim 31 , comprising contacting the first layer of first particles and the second layer of second particles with the degrading agent for about 10 seconds to about 20 minutes. 
     
     
         40 . The method of  claim 31 , wherein the solid support comprises a surface, wherein the surface comprises a plurality of wells separated from each other by interstitial regions on the surface. 
     
     
         41 . The method of  claim 31 , wherein the solid support comprises about 1×10 5  to about 5×10 10  wells. 
     
     
         42 . The method of  claim 31 , wherein the average longest dimension of the first particle and second particle is about 100 nm to about 3,000 nm. 
     
     
         43 . The method of  claim 31 , wherein the average longest dimension of the first degradable particle core and the second degradable core is about 100 nm to about 3,000 nm. 
     
     
         44 . The method of  claim 31 , wherein the first degradable particle core and the second degradable particle core comprise a metal-organic framework (MOF) core. 
     
     
         45 . The method of  claim 31 , wherein the first degradable particle core and the second degradable particle core independently comprise a Isoreticular Metal-Organic Framework (IR-MOF) core, Zeolitic Imidazolate Framework (ZIF) core, Porous Coordination Network (PCN) core, Materials Institute Lavoisier (MIL) MOF core, Porous Coordination Polymer (PCP) core, or University of Oslo (UiO) MOF core. 
     
     
         46 . The method of  claim 44 , wherein the MOF particle is a Zeolitic Imidazolate Framework 8 (ZIF-8) core or a UiO-66 MOF core. 
     
     
         47 . The method of  claim 31 , wherein the first polymer shell and the second polymer shell independently comprise polyacrylamide (AAm), poly-N-isopropylacrylamide, poly N-isopropylpolyacrylamide, sulfobetaine acrylate (SBA), carboxybetaine acrylate (CBA), phosphorylcholine acrylate (PCA), sulfobetaine methacrylate (SBMA), carboxybetaine methacrylate (CBMA), phosphorylcholine methacrylate (PCMA), polyethylene glycol acrylate, methacrylate, polyethylene glycol (PEG)-thiol/PEG-acrylate, acrylamide/N,N′-bis(acryloyl)cystamine (BACy), PEG/polypropylene oxide (PPO), polyacrylic acid, poly(hydroxyethyl methacrylate) (PHEMA), poly(methyl methacrylate) (PMMA), poly(N-isopropylacrylamide) (PNIPAAm), poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), poly(vinylsulfonic acid) (PVSA), poly(L-aspartic acid), poly(L-glutamic acid), polylysine, glicydyl methacrylate (GMA), glicydyl methacrylate (GMA) azide, hydroxyethylmethacrylate (HEMA), hydroxyethylacrylate (HEA), hydroxypropylmethacrylate (HPMA), polyethylene glycol methacrylate (PEGMA), polyethylene glycol acrylate (PEGA), isocyanatoethyl methacrylate (IEM), or a copolymer thereof. 
     
     
         48 . The method of  claim 31 , wherein the first polymer shell and the second polymer shell independently comprises polyacrylamide (AAm), glicydyl methacrylate (GMA), polyethylene glycol methacrylate (PEGMA), polyethylene glycol acrylate (PEGA), isocyanatoethyl methacrylate (IEM), or a copolymer thereof. 
     
     
         49 . The method of  claim 31 , wherein the first bioconjugate reactive moiety and the second bioconjugate reactive moiety are independently an amine moiety, aldehyde moiety, alkyne moiety, azide moiety, carboxylic acid moiety, dibenzocyclooctyne (DBCO) moiety, tetrazine moiety, epoxy moiety, isocyanate moiety, furan moiety, maleimide moiety, thiol moiety, or transcyclooctene (TCO) moiety.