Search

Current interest in nanoparticle ensembles is motivated by their collective synergetic properties that are distinct from or better than those of individual nanoparticles and their bulk counterparts. These new advanced optical, electronic, magnetic, and catalytic properties can find applications in advanced nanomaterials and functional devices, if control is achieved over nanoparticle organization. Self-assembly offers a cost-efficient approach to produce ensembles of nanoparticles with well-defined and predictable structures. Nanoparticles functionalized with polymer molecules are promising building blocks for self-assembled nanostructures, due to the comparable dimensions of macromolecules and nanoparticles, the ability to synthesize polymers with various compositions, degrees of polymerization, and structures, and the ability of polymers to self-assemble in their own right. Moreover, polymer ligands can endow additional functionalities to nanoparticle assemblies, thus broadening the range of their applications.In this Account, we describe recent progress of our research groups in the development of new strategies for the self-assembly of nanoparticles tethered to macromolecules. At the beginning of our journey, we developed a new approach to patchy nanoparticles and their self-assembly. In a thermodynamically driven strategy, we used poor solvency conditions to induce homopolymer surface segregation in pinned micelles (patches). Patchy nanoparticles underwent self-assembly in a well-defined and controlled manner. Following this work, we overcame the limitation of low yield of the generation of patchy nanoparticles, by using block copolymer ligands. For block copolymer-capped nanoparticles, patch formation and self-assembly were "staged" by using distinct stimuli for each process. We expanded this work to the generation of patchy nanoparticles via dynamic exchange of block copolymer molecules between the nanoparticle surface and micelles in the solution. The scope of our work was further extended to a series of strategies that utilized the change in the configuration of block copolymer ligands during nanoparticle interactions. To this end, we explored the amphiphilicity of block copolymer-tethered nanoparticles and complementary interactions between reactive block copolymer ligands. Both approaches enabled exquisite control over directional and self-limiting self-assembly of complex hierarchical nanostructures. Next, we focused on the self-assembly of chiral nanostructures. To enable this goal, we attached chiral molecules to the surface of nanoparticles and organized these hybrid building blocks in ensembles with excellent chiroptical properties. In summary, our work enables surface engineering of polymer-capped nanoparticles and their controllable and predictable self-assembly. Future research in the field of nanoparticle self-assembly will include the development of effective characterization techniques, the synthesis of new functional polymers, and the development of environmentally responsive self-assembly of polymer-capped nanoparticles for the fabrication of nanomaterials with tailored functionalities.

Tumor fibrotic stroma forms complex barriers for therapeutic nanomedicine. Although nanoparticle vehicles are promising in overcoming biological barriers for drug delivery, fibrosis causes hypoxia, immunosuppression and limited immunocytes infiltration, and thus reduces antitumor efficacy of nanosystems. Herein, we report the development of cancer-associated fibroblasts (CAFs) responsive honeycomb-like nanoassemblies of carbon dots (CDs) to spatially program the delivery of multiple therapeutics for enhanced antitumor chemoimmunotherapy. Doxorubicin (DOX) and immunotherapeutic enhancer (Fe ions) are immobilized on the surface of CDs, whereas tumor microenvironment modifier (losartan, LOS) is encapsulated within the mesopores. The drugs-loaded nanoassemblies disassociate into individual CDs to release LOS to mitigate stroma and hypoxia in response to CAFs. The individual CDs carrying DOX and Fe ion efficiently penetrate deep into tumor to trigger intensified immune responses. Our in vitro and in vivo studies show that the nanoassemblies exhibit effective T cells infiltration, tumor growth inhibition and lung metastasis prevention, thereby providing a therapeutic platform for desmoplasia solid tumor.

Polymer-grafted hairy nanoparticles (HNPs) that combine the unique properties of inorganic nanoparticles (NPs) and polymers are attractive building blocks for the layer-by-layer assembly of functional hybrid materials, but the adsorption behaviors of HNPs on substrates remain unclear. This article describes a systematic study on the adsorption behaviors of charged polymer-grafted HNPs on oppositely charged substrates in different solvent media via a combination of experiments and simulations. It is shown in simulations that the adsorption process of HNPs is associated with the release of counterions around charged polymers on HNPs, thus resulting in a higher energy barrier of NP adsorption than bare NPs without charged polymer tethers. This energy barrier decreases with decreasing the dielectricity of solvents or ionization degree of grafted polymers or increasing ionic strength of the solution. Furthermore, the theoretical prediction is confirmed in experiments by using a model system of poly(acrylic acid)-grafted silica NPs and poly(diallyldimethylammonium chloride)-modified wafers. The work provides guidance for the electrostatic assembly of HNPs into functional hybrid composites with applications in membranes, optical devices, and biomedicines.

The clearance of nanoparticles (NPs) by mononuclear phagocyte system (MPS) from blood leads to high liver and spleen uptake and negatively impacts their tumor delivery efficiency. Here we systematically evaluated the in vitro and in vivo nanobio interactions of a two-dimensional (2D) model, gold (Au) nanorings, which were compared with Au nanospheres and Au nanoplates of similar size. Among different shapes, Au nanorings achieved the lowest MPS uptake and highest tumor accumulation. Among different sizes, 50 nm Au nanorings showed the highest tumor delivery efficiency. In addition, we demonstrated the potential use of Au naonrings in photoacoustic imaging and photothermal therapy. Thus, engineering the shape, surface area, and size of Au nanostructures is important in controlling NP-MPS interactions and improving the tumor uptake efficiency.

Nanoparticle (NP)‐based vehicles are attractive for biomedical delivery and therapy, owing to improved therapeutic efficiency and reduced adverse effects compared to free drugs. Uncontrolled NP heterogeneity at the suspension level or single particle level poses grand challenges in the effective use of NPs for biology and medicines. Precision nanoparticles (PNPs) are a class of discrete nanostructures exhibiting elaborately tailored surface or structural heterogeneity, but minimal variations between nanostructures in one solution. Benefiting from their precisely controlled NP heterogeneity, PNPs have emerged as promising platforms for modulating various biological processes to improve the biomedical performance of NP‐based vehicles. This review summarizes recent advances in the development of precisely tailored PNPs for biomedical applications, with an emphasis on the nano‐bio interactions, and drug delivery and therapy. We start with a brief overview of the major categories of PNPs and their fabrication strategies (section 2). We then focus on reviewing the use of PNPs for enhancing biomolecular recognition or detection, regulating the NP‐protein interactions, modulating the NP‐biomembrane interactions, and improving the biological delivery and therapy (section 3). Finally, we discuss the challenges and perspectives on the design and use of PNPs for biomedical applications (section 4).

This article describes a nanoplatform based on matrix metalloproteinase (MMP)-responsive gold nanoparticles (AuNPs) for tumor-targeted photoacoustic (PA) imaging-guided photothermal therapy and drug delivery. AuNPs were grafted with complementary DNA strands, tethered with doxorubicin and coated with poly(ethylene glycol) via a thermal-labile linker and a MMP-cleavable peptide, respectively. The nanoprobes remained well-isolated in healthy tissues, but formed aggregates rapidly under MMP-abundant conditions. The DNA hybridization-induced assembly of the nanoprobes led to prolonged tumor retention and strong near-infrared (NIR) absorption, which is beneficial to deep-tissue imaging and therapy. Compared with MMP-inert nanoprobes, our platform demonstrated significantly enhanced efficiency in PA imaging and photothermal conversion upon NIR irradiation. Meanwhile, doxorubicin could be released rapidly in response to the localized elevation of temperature, leading to synergistic chemo-photothermal therapy. The unique nanoplatform may find applications in effective disease control by delivering imaging and therapy to tumors with high specificity, safety, and universality.

We present a reconstituted lipoprotein-based nanoparticle platform comprising a curcumin fluorescent motif and an NIR responsive gold core. This multifunctional nanosystem is successfully used for aggregation-dependent fluorescence detection and photothermal disassembly of insoluble amyloid aggregates.

Cancer evolves to evade or compromise the surveillance of the immune system, and cancer immunotherapy aims to harness the immune system in order to inhibit cancer development. Unmethylated CpG dinucleotide-containing oligonucleotides (CpG), a class of potent adjuvants that activate the toll-like receptor 9 (TLR9) located in the endolysosome of many antigen-presenting cells (APCs), are promising for cancer immunotherapy. However, clinical application of synthetic CpG confronts many challenges such as suboptimal delivery into APCs, unfavorable pharmacokinetics caused by limited biostability and short in vivo half-life, and side effects associated with leaking of CpG into the systemic circulation. Here we present DNA-inorganic hybrid nanovaccines (hNVs) for efficient uptake into APCs, prolonged tumor retention, and potent immunostimulation and cancer immunotherapy. hNVs were self-assembled from concatemer CpG analogs and magnesium pyrophosphate (Mg2PPi). Mg2PPi renders hNVs resistant to nuclease degradation and thermal denaturation, both of which are demanding characteristics for effective vaccination and the storage and transportation of vaccines. Fluorophore-labeled hNVs were tracked to be efficiently internalized into the endolysosomes of APCs, where Mg2PPi was dissolved in an acidic environment and thus CpG analogs were exposed to hNVs. Internalized hNVs in APCs led to (1) elevated secretion of proinflammatory factors, and (2) elevated expression of co-stimulatory factors. Compared with molecular CpG, hNVs dramatically prolonged the tissue retention of CpG analogs and reduced splenomegaly, a common side effect of CpG. In a melanoma mouse model, two injections of hNVs significantly inhibited the tumor growth and outperformed the molecular CpG. These results suggest hNVs are promising for cancer immunotherapy.

Organized arrays of anisotropic nanoparticles show electronic and optical properties that originate from the coupling of shape-dependent properties of the individual nanorods. The organization of nanorods in a controllable and predictable way provides a route to the fabrication of new materials and functional devices. So far, significant progress has been achieved in the self-assembly of nanorod arrays, yet the realization of a range of different structures requires changing the surface chemistry of the nanoparticles. We organized metal nanorods in structures with varying geometries by using a striking analogy between amphiphilic ABA triblock copolymers and the hydrophilic nanorods tethered with hydrophobic polymer chains at both ends. The self-assembly was tuneable and reversible and it was achieved solely by changing the solvent quality for the constituent blocks. This approach provides a new route to the organization of anisotropic nanoparticles by using the strategies that are established for the self-assembly of block copolymers.

Colloidal molecules constructed from polymers and nanoparticles (NPs) have recently emerged as a novel class of building blocks for assembling functional hybrid materials. Particularly, self-assembly of amphiphilic block copolymer (BCP)-tethered NPs (BNPs) has shown great promise in the nanoscale design of functional hybrid materials. On the one hand, structurally the BNPs can be considered as molecular equivalents that are capable of self-assembly at multiple hierarchical levels. On the other hand, the assembly of BNPs shows significant differences from molecular assembly due to their large dimension, complex geometry, and multi-scale interactions involved in the assembly process. The manipulation of BCPs localized near the surface of the NPs offers an effective tool for engineering the interactions between NPs and hence the complexity of NP assembly. In this Feature Article, recent progresses on the self-assembly of BNPs into functional materials are summarized. First, major strategies for assembling amphiphilic BNPs are highlighted. Secondly, the application of hybrid nanostructures (e.g., vesicles) assembled from BNPs in the field of biomedical imaging and delivery is discussed. Finally, current challenges and perspectives at this frontier are outlined.

Hierarchical assembling of gold nanoparticles (GNPs) allows one to engineer the localized surface plasmon resonance (LSPR) peaks to the near-infrared (NIR) region for enhanced photothermal Therapy (PTT). Herein we report a novel theranostic platform based on biodegradable plasmonic gold nanovesicles for photoacoustic (PA) Imaging and PTT. The disulfide bond (S-S) termed PEG-b-PCL block copolymer graft allows dense packing of GNPs during the assembly process and induces ultra-strong plasmonic coupling effect between adjacent GNPs. The strong NIR absorption induced by plasmon coupling and very high photothermal conversion efficiency (η= 37 %) enable simultaneous thermal/PA imaging and enhanced PTT efficacy with improved clearance of the dissociated particles after the completion of PTT. These vesicle-architectures assembling of various nanocrystals with tailored optical, magnetic, and electronic properties opens new possibilities for constructing multifunctional biodegradable platforms for biomedical applications, particularly in cancer theranotics.

Amphiphilic plasmonic micelle-like nanoparticles (APMNs) composed of gold nanoparticles (AuNPs) and amphiphilic block copolymers (BCPs) structurally resemble polymer micelles with well-defined architectures and chemistry. The APMNs can be potentially considered as a prototype for modeling a higher-level self-assembly of micelles. The understanding of such secondary self-assembly is of particular importance for the bottom-up design of new hierarchical nanostructures. This article describes the self-assembly, modeling, and applications of APMN assemblies in selective solvents. In a mixture of water/tetrahydrofuran, APMNs assembled into various superstructures, including unimolecular micelles, clusters with controlled number of APMNs, and vesicles, depending on the lengths of polymer tethers and the sizes of AuNP cores. The delicate interplay of entropy and enthalpy contributions to the overall free energy associated with the assembly process, which is strongly dependent on the spherical architecture of APMNs, yields an assembly diagram that is different from the assembly of linear BCPs. Our experimental and computational studies suggested that the morphologies of assemblies were largely determined by the deformability of the effective nanoparticles (that is, nanoparticles together with tethered chains as a whole). The assemblies of APMNs resulted in strong absorption in near-infrared range due to the remarkable plasmonic coupling of Au cores, thus facilitating their biomedical applications in bioimaging and photothermal therapy of cancer.

Asymmetric multicomponent nanoparticles (AMNPs) offer new opportunities for new-generation materials with improved or new synergetic properties not found in their individual components. There is, however, an urgent need for a synthetic strategy capable of preparing hybrid AMNPs with fine-tuned structural and compositional complexities. Herein, we report a new paradigm for the controllable synthesis of polymer/metal AMNPs with well-controlled size, shape, composition, and morphology by utilizing interfacial polymerization. The hybrid AMNPs display a new level of structural–architectural sophistication, such as controlled domain size and the number of each component of AMNPs. The approach is simple, versatile, cost-effective, and scalable for synthesizing large quantities of AMNPs. Our method may pave a new route to the design and synthesis of advanced breeds of building blocks for functional materials and devices.