Hierarchical Self‐assembly of Discrete Metal–Organic Cages into Supramolecular Nanoparticles for Intracellular Protein Delivery

Abstract

Hierarchical self-assembly (HAS) is ap owerful approach to create supramolecular nanostructures for biomedical applications.T his potency,h owever,i sg enerally challenged by the difficulty of controlling the HAS of biomacromolecules and the functionality of resulted HAS nanostructures.H erein, we report am odular approachf or controlling the HAS of discrete metal-organic cages (MOC) into supramolecular nanoparticles,a nd its potential for intracellular protein delivery and cell-fate specification. The hierarchical coordination-driven self-assembly of adamantane-functionalized M 12 L 24 MOC (Ada-MOC) and the hostguest interaction of Ada-MOC with b-cyclodextrin-conjugated polyethylenimine (PEI-bCD) affords upramolecular nanoparticles in ac ontrollable manner.H AS maintains high efficiency and orthogonality in the presence of protein, enabling the encapsulation of protein into the nanoparticles for intracellular protein delivery for therapeutic application and CRISPR/Cas9 genome editing.

Tuning the Size and Geometry of Heteroleptic Coordination Cages by Varying the Ligand Bent Angle

“…Cage-like structures of the formula [Pd n L 2n ] 2n + have been investigated extensively over the last years, and applications in medicinal chemistry, [28][29][30][31][32][33][34][35][36] catalysis, [37][38][39][40][41] and materials science [42][43][44][45][46][47] reported to date display high symmetry. Low-symmetry assemblies could show interesting new properties.…”

“…Cage‐like structures of the formula [Pd n L 2 n ] 2 n + have been investigated extensively over the last years, and applications in medicinal chemistry, [28–36] catalysis, [37–41] and materials science [42–47] have emerged. Most of the [Pd n L 2 n ] 2 n + complexes reported to date display high symmetry.…”

Metallacycles, metallacages, and their aggregate/optical behavior

“…The structure of M60 [63a] ; (B) mice bearing different sizes of tumors after the injection of MNPs [63a] ; (C) the structures of M61-63 [63b] ; (D) images of a mouse and its different organs after the intratumoral injection of M62-based nanoparticles [63b] ; (E) the structures of M64 and M65 [63c] ; (F) 4T1 orthotopic tumors harvested from mice that received different treatments [63c] ; and (G) scheme of M66 and β-cyclodextrin-conjugated polyethylenimine along with intracellular protein delivery via supramolecular nanoparticles. [60] Copyright 2020, Wiley-VCH, Copyright 2019 American Chemical Society process increases the number of excited photocatalysts (eosin Y * ) that undergo a catalytic cycle to increase the catalytic activity. Moreover, hydrogen is produced by the combination of dissociated hydrogen radicals, offering a pathway for storing light energy (Figure 8G).…”

“…By utilizing the relationships between these factors and the resultant optical properties, MOCs can be designed to serve as light-emitting materials, [56] light-harvesting systems, [57] information-encryption media, [58] isomerization controllers, [59] protein-delivery carriers, [60] bacterial imaging materials [61] and antibacterial agents (Scheme 2). [62] Most importantly, as theranostic agents, [63] MOCs have been applied in the fields of chemotherapy, photochemotherapy, photodynamic therapy, NIR-II theranostics, etc.…”

In‐Situ Encapsulation of Protein into Nanoscale Hydrogen‐Bonded Organic Frameworks for Intracellular Biocatalysis

“…Enzyme catalysis in living cells not only enables in situ monitoring of cellular metabolism for disease diagnosis, [21] but also offers promising therapeutic benefits for defective enzyme‐induced diseases [22–24] . Native enzymes, however, tend to be unable to spontaneously enter cells and are also prone to degradation in complicated environment, [25, 26] making the development of delivery system to facilitate the cellular internalization of proteins especially crucial for enzyme catalysis‐associated disease diagnosis and therapy [27–37] . One attractive strategy to enhance the cellular uptake of enzymes is to immobilize them within nanoscale porous materials [38] .…”