Shieldable Tumor Targeting Based on pH Responsive Self-Assembly/Disassembly of Gold Nanoparticles

Abstract

A new approach to shield/deshield ligands for controllable tumor targeting was reported, which was based on amphiphilic self-assembly and disassembly of gold nanoparticles (Au NPs). Thanks to the excellent pH response of the system, glycyrrhetinic acid (GA) ligands can be buried inside the Au NPs' assembly at normal tissue pH (pH 7.4), while exposed when the nanostructure is disassembled at tumor extracellular pH (pHe 6.8). Hydrophobic GA molecules not only acted as ligands targeting tumor cells but also provided the major interparticle attractive force for Au NPs' assembling. An ordered assembly of Au NPs with regular shape, proper size and ultrasharp pH sensitivity (ΔpH ∼ 0.2) was achieved by fine-tuning of materials modified on Au NPs. Mechanism studies for assembly and disassembly of Au NPs indicated the possibility of a GA shield when the assembly formed, which was further demonstrated by bovine serum albumin absorption and cellular uptake. The assembly/disassembly process was reversible within extrinsic pH changes, which provides a perspective for reversible tumor targeting.

Colloidal Clusters of Plasmonic Nanoparticles with Controlled Topological Parameters

“…[28,29] The structurals tability of NP assemblies under various pH and temperature conditions is oneo ft he most criticali ssues for their applications in SERS-based bio/chemicals ensing and catalytic or photocatalytic reactions. Contrary to conventional NP assemblies generatedu sing DNA-or molecule-mediated assembly techniques, in whichs tructural integrity is vulnerable to the changes in their physicochemical environments, [10][11][12][13] the prepared Au NPCs showed remarkable structural stability under various conditions. For instance, the UV-vis extinction spectra of the Au NPCs measured under variousp Hc onditions ranging from pH 2t o1 2, which were adjusted with HNO 3 and NaOH, showedm inute changes in the SPR characteristics upon the change in pH (Figure 2a-e).…”

“…In this regard, numerous approaches for the assembly of NPs in colloidal states have been developed, in which specific molecular or charge interactions between passivating ligands on NP surfaces, solvent‐ligand interactions, and van der Waals (vdW) interactions between NPs have been exploited to the formation of NP assemblies . However, the extent and features of these interactions that can drive the assembly of NPs are very sensitive to their physicochemical environments, including solvent, pH, temperature, light, ionic strength, and foreign organic or inorganic species, and the balance between the repulsive and attractive forces applied among NPs is hard to be controlled . Accordingly, the generation of robust colloidal NP assemblies with fine control over their topological parameters, such as the dimension and morphology of assemblies, average number and size of constituent NPs in individual assemblies, and shape homogeneity of NPs, is still a challenging task.…”

“…[8,9] However,t he extent and features of these interactions that can drive the assembly of NPs are very sensitive to their physicochemical environments,i ncluding solvent, pH, temperature, light, ionic strength,a nd foreigno rganic or inorganic species, and the balance between the repulsivea nd attractive forces applied amongN Ps is hard to be controlled. [2,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Accordingly,t he generationo fr obust colloidal NP assemblies with fine control over their topological parameters, such as the dimension and morphologyofassemblies, average number and size of constituent NPs in individual assemblies, and shape homogeneity of NPs, is still achallenging task.…”

Dynamic Nanoparticle Assemblies for Biomedical Applications

“…Tian et al prepared a tertiary amine derivative of glycyrrhetinic acid (GA) together with lipoyl tertiary amines as pH‐responsive ligands for self‐assembly/disassembly of gold nanoparticles . In neutral environments, a hydrophobic reaction between ligands leads to a nanoparticle self‐assembly, which is subsequently dispersed into separate nanoparticles in a more acidic environment due to the presence of positively charged amino groups.…”

Two‐Step Assembly of Thermoresponsive Gold Nanorods Coated with a Single Kind of Ligand

“…However, the reversibility of the multistep assembly process has not been exploited sufficiently. For the fabrication of sophisticated assemblies with dynamic structural changes, hierarchical structures composed of nanoparticles require controllable reversibility of assembly/disassembly in response to changes in the environment, [27] such as temperature, [28][29][30][31][32][33] pH, [34][35][36] and light. [37,38]…”