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In this Perspective, we present a unique approach to the design and synthesis of giant molecules based on “nanoatoms” for engineering structures across multiple length scales and controlling their macroscopic properties. Herein, “nanoatoms” refer to shape-persistent molecular nanoparticles (MNPs) with precisely defined chemical structures and surface functionalities that can serve as elemental building blocks for the precision synthesis of giant molecules by methods such as sequential “click” approach. Typical “nanoatoms” include those MNPs based on fullerenes, polyhedral oligomeric silsesquioxanes, polyoxometalates, and folded globular proteins. The resulting giant molecules are precisely defined macromolecules. They include, but are not limited to, giant surfactants, giant shape amphiphiles, and giant polyhedra. Giant surfactants are polymer tail-tethered “nanoatoms” where the two components have drastic chemical differences to impart amphiphilicity. Giant shape amphiphiles not only are built up by covalently bonded MNPs of distinct shapes where the self-assembly is driven by chemical interactions but also are largely influenced by the packing constraints of each individual shape. Giant polyhedra are either made of a large MNP or by deliberately placing “nanoatoms” at the vertices of a polyhedron. In general, giant molecules capture the essential structural features of their small-molecule counterparts in many ways but possess much larger sizes. They are recognized in certain cases as size-amplified versions of those counterparts, and often, they bridge the gap between small molecules and traditional macromolecules. Highly diverse, thermodynamically stable and metastable hierarchal structures are commonly observed in the bulk, thin film, and solution states of these giant molecules. Controlled structural variations by precision synthesis further reveal a remarkable sensitivity of their self-assembled structures to the primary chemical structures. Unconventional nanostructures can be obtained in confined environments or through directed self-assembly. All the results demonstrate that MNPs are unique elements for macromolecular science, providing a versatile platform for engineering nanostructures that are not only scientifically intriguing but also technologically relevant.

Self-assembly of rigid building blocks with explicit shape and symmetry is substantially influenced by the geometric factors and remains largely unexplored. We report the selective assembly behaviors of a class of precisely defined, nanosized giant tetrahedra constructed by placing different polyhedral oligomeric silsesquioxane (POSS) molecular nanoparticles at the vertices of a rigid tetrahedral framework. Designed symmetry breaking of these giant tetrahedra introduces precise positional interactions and results in diverse selectively assembled, highly ordered supramolecular lattices including a Frank-Kasper A15 phase, which resembles the essential structural features of certain metal alloys but at a larger length scale. These results demonstrate the power of persistent molecular geometry with balanced enthalpy and entropy in creating thermodynamically stable supramolecular lattices with properties distinct from those of other self-assembling soft materials.

In the past decade, nanomedicine with its promise of improved therapy and diagnostics has revolutionized conventional health care and medical technology. Dendrimers and dendrimer-based therapeutics are outstanding candidates in this exciting field as more and more biological systems have benefited from these starburst molecules. Anticancer agents can be either encapsulated in or conjugated to dendrimer and be delivered to the tumour via enhanced permeability and retention (EPR) effect of the nanoparticle and/or with the help of a targeting moiety such as antibody, peptides, vitamins, and hormones. Imaging agents including MRI contrast agents, radionuclide probes, computed tomography contrast agents, and fluorescent dyes are combined with the multifunctional nanomedicine for targeted therapy with simultaneous cancer diagnosis. However, an important question reported with dendrimer-based therapeutics as well as other nanomedicines to date is the long-term viability and biocompatibility of the nanotherapeutics. This critical review focuses on the design of biocompatible dendrimers for cancer diagnosis and therapy. The biocompatibility aspects of dendrimers such as nanotoxicity, long-term circulation, and degradation are discussed. The construction of novel dendrimers with biocompatible components, and the surface modification of commercially available dendrimers by PEGylation, acetylation, glycosylation, and amino acid functionalization have been proposed as available strategies to solve the safety problem of dendrimer-based nanotherapeutics. Also, exciting opportunities and challenges on the development of dendrimer-based nanoplatforms for targeted cancer diagnosis and therapy are reviewed (404 references).

Triticum urartu (diploid, AA) is the progenitor of the A subgenome of tetraploid (Triticum turgidum, AABB) and hexaploid (Triticum aestivum, AABBDD) wheat. Genomic studies of T. urartu have been useful for investigating the structure, function and evolution of polyploid wheat genomes. Here we report the generation of a high-quality genome sequence of T. urartu by combining bacterial artificial chromosome (BAC)-by-BAC sequencing, single molecule real-time whole-genome shotgun sequencing , linked reads and optical mapping. We assembled seven chromosome-scale pseudomolecules and identified protein-coding genes, and we suggest a model for the evolution of T. urartu chromosomes. Comparative analyses with genomes of other grasses showed gene loss and amplification in the numbers of transposable elements in the T. urartu genome. Population genomics analysis of 147 T. urartu accessions from across the Fertile Crescent showed clustering of three groups, with differences in altitude and biostress, such as powdery mildew disease. The T. urartu genome assembly provides a valuable resource for studying genetic variation in wheat and related grasses, and promises to facilitate the discovery of genes that could be useful for wheat improvement.

Structural colors arising from interactions of light with submicron scale periodic structures have been found in many species across all taxa, serving multiple biological functions including sexual signaling, camouflage, and aposematism. Directly inspired by the extensive use of self-assembled melanosomes to produce colors in avian feathers, we set out to synthesize and assemble polydopamine-based synthetic melanin nanoparticles in an effort to fabricate colored films. We have quantitatively demonstrated that synthetic melanin nanoparticles have a high refractive index and broad absorption spanning across the UV-visible range, similar to natural melanins. Utilizing a thin-film interference model, we demonstrated the coloration mechanism of deposited films and showed that the unique optical properties of synthetic melanin nanoparticles provide advantages for structural colors over other polymeric nanoparticles (i.e., polystyrene colloidal particles).

SummaryA costimulatory signal through B7 to its counter-receptor CD28 on T cells enhances T cell activation. We have generated recombinant retroviruses containing cDNA for routine B7 and transduced a pand of murine tumor lines with varying immunogenicity to study the effect of B7 costimulation on antitumor immunity. In contrast to the progressive outgrowth of all wildtype (B7-) tumors in unimmunized syngeneic mice, four immunogenic tumors, lymphoma RMA, EL4, mastocytoma P815, and melanoma E6B2, regressed completely when transduced with the B7 gene. In contrast, four nonimmunogenic tumors, sarcomas MCA101, MCA102, and Agl04, and mdanoma B16, remained tumorigenic after transduction of the B7 gene. Immunization with B7-tranduced immunogenic tumors enhanced protective immunity and increased specific cytotoxic T lymphocyte (CTL) activity against the respective wild-type tumors as compared to immunization with nontransduced or mock-transduced tumors. Moreover, cocultivation of CTL with B7-transduced EL4 cells augmented the specificity of tumor-reactive CTL in long-term cultures. Treatment by injection of B7-transduced tumor cells cured 60% of mice with established wild-type EL4 lymphoma. In contrast, immunization with nonimmunogenic tumors transduced with B7 did not provide protective immunity and did not increase specific CTL activity. Our results show that tumor immunogenicity is critical to the outcome of costimulation of T cell-mediated tumor immunity by B7.

Bread wheat expanded its habitats from a small core area of the Fertile Crescent to global environments within ~10,000 years. Genetic mechanisms of this remarkable evolutionary success are not well understood. By whole-genome sequencing of populations from 25 subspecies within genera Triticum and Aegilops, we identified composite introgression from these wild populations contributing 13%~36% of the bread wheat genome, which tremendously increased the genetic diversity of bread wheat and allowed its divergent adaptation. Meanwhile, convergent adaption to human selection showed 2-to 16-fold enrichment relative to random expectation in Triticum species despite their drastic differences in ploidy levels and growing zones, indicating the vital importance of adaptive constraints in the success of bread wheat. These results showed the genetic necessities of wheat as a global crop and provided new perspectives on leveraging adaptation success across species for crop improvement.