Unimolecular Nanoparticles Research Articles

Diverse superlattices constructed via perylene bisimide type of giant shape amphiphiles: Assisted with unimolecular nanoparticles

Complex superlattices formed by spherical motifs in soft matter have attracted more interest in the last two decades. Herein, we report the supramolecular assembly behaviors of four types of giant shape amphiphiles composed of perylene bisimide and isooctyl-polyhedral oligomeric silsesquioxane (OPOSS) with different linkages. The glass forming temperatures of these giant shape amphiphiles decrease from 10.3 °C to -14.3 °C with increasing of the linker length. These giant molecules can self-assemble into well-ordered Frank-Kasper (FK) A15 phases. Furthermore, blending with unimolecular nanoparticles, diverse superlattices including FK (such as Laves C15, also called MgCu2) and quasi-FK (such as NaZn13) phases are found. This work could provide a basic understanding towards the phase behaviors of spherical motifs constructed by giant molecules, as well as supports our previous findings about binary blending in complex superlattices formation.

Unimolecular Nanoparticles toward More Precise Regulations of Self‐Assembled Superlattices in Soft Matter

AbstractThe hierarchical self‐assembly process opens up great potential for the construction of nanostructural superlattices. Precise regulation of self‐assembled superlattices, however, remains a challenge. Even when the primary molecules are precise, the supramolecular motifs (or secondary building blocks) can vary dramatically. In the present work, we propose the concept of unimolecular nanoparticles (UMNPs). The UMNPs act as the supramolecular motif and directly pack into the superlattices. A highly branched giant molecule is presented. We systematically explore its conformations and the superlattice of this giant molecule. Moreover, intriguing complex phases are discovered when blending this UMNP with other conventional giant molecules. These binary mixtures provide direct evidence to support our previously proposed self‐sorting process in the self‐assembly of “soft alloys”. The concept of UMNPs offers a unique approach toward more precise regulation of self‐assembled superlattices in soft matter.

Unimolecular Nanoparticles toward More Precise Regulations of Self-Assembled Superlattices in Soft Matter.

The hierarchical self-assembly process opens up great potential for the construction of nanostructural superlattices. Precise regulation of self-assembled superlattices, however, remains a challenge. Even when the primary molecules are precise, the supramolecular motifs (or secondary building blocks) can vary dramatically. In the present work, we propose the concept of unimolecular nanoparticles (UMNPs). The UMNPs act as the supramolecular motif and directly pack into the superlattices. A highly branched giant molecule is presented. We systematically explore its conformations and the superlattice of this giant molecule. Moreover, intriguing complex phases are discovered when blending this UMNP with other conventional giant molecules. These binary mixtures provide direct evidence to support our previously proposed self-sorting process in the self-assembly of "soft alloys". The concept of UMNPs offers a unique approach toward more precise regulation of self-assembled superlattices in soft matter.

Unimolecular Nano-contrast Agent with Ultrahigh Relaxivity and Very Long Retention for Magnetic Resonance Lymphography.

Magnetic resonance (MR) imaging is very important for noninvasive lymphography. However, the present MR contrast agents still cannot supply strong enough tissue contrast and long observation window. To improve the performance of contrast agents, we introduce one-dimensional unimolecular nanoparticles with a confined and compact poly(acrylic acid) core as nanoparticulate chelates of gadolinium ions. Thus, obtained nanoparticulate T1 contrast agents give r1 relaxivity as high as 136.3 mM-1·s-1 under 3.0 T. By injection at the footpad of mice, the contrast agents provide excellent contrast enhancement of lymphatic drainage and they may arrive at popliteal lymph nodes within 30 min and reside for more than 80 h. High performance of the present contrast agent is attributed to the confined and compact core of materials that increase hydration number, intershell water diffusion, and decrease rotational motion.

Biomimetic, ROS-detonable nanoclusters — A multimodal nanoplatform for anti-restenotic therapy

The long-term success of endovascular intervention has long been overshadowed by vessel re-occlusion, also known as restenosis. Mainstream anti-restenotic devices, such as drug-eluting stent (DES) and drug-coated balloon (DCB), were recently shown with suboptimal performances and life-threatening complications, thereby underpinning the urgent need for alternative strategies with enhanced efficacy and safety profile. In our current study, we engineered a multimodal nanocluster formed by self-assembly of unimolecular nanoparticles and surface coated with platelet membrane, specifically tailored for precision drug delivery in endovascular applications. More specifically, it incorporates the combined merits of platelet membrane coating (lesion targetability and biocompatibility), reactive oxygen species (ROS)-detonable “cluster-bomb” chemistry (to trigger the large-to-small size transition at the target site, thereby achieving longer circulation time and higher tissue penetration), and sustained drug release. Using RVX-208 (an emerging anti-restenotic drug under clinical trials) as the model payload, we demonstrated the superior performances of our nanocluster over conventional poly(lactic-co-glycolic acid) (PLGA) nanoparticle. In cultured vascular smooth muscle cell (VSMC), the drug-loaded nanocluster induced effective inhibition of proliferation and protective gene expression (e.g., APOA-I) with a significantly reduced dosage of RVX-208 (1 μM). In a rat model of balloon angioplasty, intravenous injection of Cy5.5-tagged nanocluster led to greater lesion targetability, improved biodistribution, and deeper penetration into injured vessel walls featuring enriched ROS. Moreover, in contrast to either free drug solution or drug-loaded PLGA nanoparticle formulation, a single injection with the drug-loaded nanocluster (10 mg/kg of RVX-208) was sufficient to substantially mitigate restenosis. Additionally, this nanocluster also demonstrated biocompatibility according to in vitro cytotoxicity assay and in vivo histological and tissue qPCR analysis. Overall, our multimodal nanocluster offers improved targetability, tissue penetration, and ROS-responsive release over conventional nanoparticles, therefore making it a highly promising platform for development of next-generation endovascular therapies.

Bottlebrush Polymer Excipients Enhance Drug Solubility: Influence of End-Group Hydrophilicity and Thermoresponsiveness.

Bottlebrush polymers have great potential as vehicles to noncovalently sequester, stabilize, and deliver hydrophobic small molecule actives. To this end, we synthesized a poly(N-isopropylacrylamide-stat-N,N-dimethylacrylamide) bottlebrush copolymer using ring-opening metathesis polymerization and developed a facile method to control the thermoresponsive properties using postpolymerization modification. Six increasingly hydrophilic end-groups were installed, yielding cloud point temperature control over a range of 22-42 °C. Solubility enhancement of the antiseizure medication, phenytoin, increased significantly with the hydrophilicity of the end-group moiety. Notably, carboxylated bottlebrush copolymers solubilized formulations with higher drug loadings than linear copolymers because they exist as unimolecular nanoparticles with a synthetically defined density of polymer chains that are more stable in solution. This work provides the first investigation of bottlebrush polymers for hydrophobic noncovalent sequestration and solubilization of pharmaceuticals.

Antimicrobial Hyperbranched Polymer-Usnic Acid Complexes through a Combined ROP-RAFT Strategy.

Polymer-drug conjugates have received considerable attention over the last decades due to their potential for improving the clinical outcomes for a range of diseases. It is of importance to develop methods for their preparation that have simple synthesis and purification requirements but maintain high therapeutic efficacy and utilize macromolecules that can be cleared via natural excretory pathways upon breakdown. Herein, the combination of ring-opening polymerization (ROP) and reversible addition-fragmentation chain-transfer (RAFT) polymerization is described for the straightforward synthesis of amphiphilic, stimuli-responsive, biodegradable, and highly functionalizable hyperbranched polymers. These unimolecular nanoparticles demonstrate a versatile platform for the synthesis of polymer-drug conjugates owing to the inclusion of a Boc-protected polycarbonate moiety in either a block or random copolymer formation. A proof-of-concept study on the complexation of the poorly water-soluble antimicrobial drug usnic acid results in polymer-drug complexes with powerful antimicrobial properties against gram-positive bacteria. Therefore, this work highlights the potential of amphiphilic and biodegradable hyperbranched polymers for antimicrobial applications.

Hydrogen Bonding in a l-Glutamine-Based Polyamidoamino Acid and its pH-Dependent Self-Ordered Coil Conformation.

This paper reports on synthesis, acid–base properties, and self-structuring in water of a chiral polyamidoamino acid, M-l-Gln, obtained from the polyaddition of N,N′-methylenebisacrylamide with l-glutamine, with the potential of establishing hydrogen bonds through its prim-amide pendants. The M-l-Gln showed pH-responsive circular dichroism spectra, revealing ordered conformations. Structuring was nearly insensitive to ionic strength but sensitive to denaturing agents. The NMR diffusion studies were consistent with a population of unimolecular nanoparticles thus excluding aggregation. The M-l-Gln had the highest molecular weight and hydrodynamic radius among all polyamidoamino acids described. Possibly, transient hydrogen bonds between l-glutamine molecules and M-l-Gln growing chains facilitated the polyaddition reaction. Theoretical modeling showed that M-l-Gln assumed pH-dependent self-ordered coil conformations with main chain transoid arrangements reminiscent of the protein hairpin motif owing to intramolecular dipole moments and hydrogen bonds. The latter were most numerous at the isoelectric point (pH 4.5), where they mainly involved even topologically distant main chain amide N–H and side chain amide C=O brought to proximity by structuring. Hydrogen bonds at pH 4.5 were also suggested by variable temperature NMR. The 2D NOESY experiments at pH 4.5 confirmed the formation of compact structures through the analysis of the main chain/side chain hydrogen contacts, in line with MD simulations.

Shell of amphiphilic molecular bottlebrush matters as unimolecular micelle

Molecular bottlebrushes (MBBs) with a hydrophobic core and a hydrophilic shell may exist as well-defined unimolecular nanoparticles in water. However, they may also aggregate to form large particles if the structure of the hydrophilic and hydrophobic segments fail to be rationally controlled. Herein, a series of core-shell amphiphilic MBBs with a poly (ε-caprolactone) (PCL) backbone bearing two block copolymer side chains, poly (butyl acrylate)-b-poly ((oligo (ethylene glycol) acrylate) (PBA-b-POEGA) and poly (butyl acrylate)-b-poly (ethylene glycol) (PBA-b-PEG), were synthesized through grafting-from and grafting-onto strategies. Their hydrophilic shells are different in topology: POEGA is comblike whereas PEG is linear. The stability of the two kinds of MBB with the similar composition as unimolecular nanoparticles in water and their encapsulation capacity for guest-molecule were evaluated. Compared to the MBB with a linear PEG shell, those with comblike POEGA side chains remained stable against aggregation as demonstrated by atomic force microscopy and dynamic light scattering measurement. The MBB with a POEGA shell also displayed a much higher encapsulating capacity to a model guest molecule, pyrene, by hydrophobic interaction. This study provides guidance to the rational preparation of MBBs for applications as molecular vehicles.

A review on core-shell structured unimolecular nanoparticles for biomedical applications.

Polymeric unimolecular nanoparticles (NPs) exhibiting a core-shell structure and formed by a single multi-arm molecule containing only covalent bonds have attracted increasing attention for numerous biomedical applications. This unique single-molecular architecture provides the unimolecular NP with superior stability both in vitro and in vivo, a high drug loading capacity, as well as versatile surface chemistry, thereby making it a desirable nanoplatform for therapeutic and diagnostic applications. In this review, we surveyed the architecture of various types of polymeric unimolecular NPs, including water-dispersible unimolecular micelles and water-soluble unimolecular NPs used for the delivery of hydrophobic and hydrophilic agents, respectively, as well as their diverse biomedical applications. Future opportunities and challenges of unimolecular NPs were also briefly discussed.

Fabrication of Thermosensitive Cyclic Brush Copolymer with Enhanced Therapeutic Efficacy for Anticancer Drug Delivery.

Adaptation of cyclic brush polymer for drug delivery applications remains largely unexplored. Herein, cyclic brush copolymer of poly(2-hydroxyethyl methacrylate-g-poly(N-isopropylacrylamide-st-N-hydroxyethylacrylamide)) (cb-P(HEMA-g-P(NIPAAm-st-HEAAm))), comprising a cyclic core of PHEMA and thermosensitive brushes of statistical copolymer of P(NIPAAm-st-HEAAm), is designed and synthesized successfully via a graft-from approach using atom transfer free radical polymerization from a cyclic multimacroinitiator. The composition of the brush is optimized to endow the resulting cyclic brush copolymer with a lower critical solution temperature (LCST) slightly above the physiological temperature, but lower than the localized temperature of tumor tissue, which is suitable for the hyperthermia-triggered anticancer drug delivery. Critical aggregation concentration determination reveals better stability for the unimolecular nanoparticle formed by the cyclic brush copolymer than that formed by the bottlebrush analogue. The dramatically increased size with elevated temperatures from below to above the LCST confirms hyperthermia-induced aggregation for both formulations. Such structural destabilization promotes significantly the drug release at 40 °C. Most importantly, the drug-loaded cyclic brush copolymer shows enhanced in vitro cytotoxicity against HeLa cells than the bottlebrush counterpart. The better stability and higher therapeutic efficacy demonstrates that the thermosensitive cyclic brush copolymer is a better formulation than bottle brush copolymer for controlled drug release applications.

Solute-Triggered Morphological Transitions of an Amphiphilic Heterografted Brush Copolymer as a Single-Molecule Drug Carrier

We describe the use of an amphiphilic macromolecular brush based on poly(ethylene glycol) (PEG) and poly(d,l-lactide) (PLA) as a stabilizer of hydrophobic solutes. The brush, which in solution adopted an extended backbone conformation consequent with excluded volume effects of the side chains, retained an elongated character in water following the hydrophobic collapse of PLA and the backbone triggered by a rapid change in solvent quality. However, in the presence of hydrophobic solutes at low concentrations in a homogeneous environment, the brush formed spherical unimolecular nanoparticles achieving high solute encapsulation efficiency. As solute content increased and exceeded what appears to be a limit for intramolecular solubilization, intermolecular assembly took place along with the formation of large aggregates, the properties of which were highly dependent on the solute. This first observation of the solute-triggered unimolecular collapse of an amphiphilic macromolecular brush should find important ...

Tumor-targeted pH/redox dual-sensitive unimolecular nanoparticles for efficient siRNA delivery

A unique pH/redox dual-sensitive cationic unimolecular nanoparticle (NP) enabling excellent endosomal/lysosomal escape and efficient siRNA decomplexation inside the target cells was developed for tumor-targeted delivery of siRNA. siRNA was complexed into the cationic core of the unimolecular NP through electrostatic interactions. The cationic core used for complexing siRNA contained reducible disulfide bonds that underwent intracellular reduction owing to the presence of high concentrations of reduced glutathione (GSH) inside the cells, thereby facilitating the decomplexation of siRNA from the unimolecular NPs. The cationic polymers were conjugated onto the hyperbranched core (H40) via a pH-sensitive bond, which further facilitated the decomplexation of siRNA from the NPs. In vitro studies on the siRNA release behaviors showed that dual stimuli (pH=5.3, 10mM GSH) induced the quickest release of siRNA from the NPs. In addition, the imidazole groups attached to the cationic polymer segments enhanced the endosomal/lysosomal escape of NPs via the proton sponge effect. Intracellular tracking studies revealed that siRNA delivered by unimolecular NPs was efficiently released to the cytosol. Moreover, the GE11 peptide, an anti-EGFR peptide, enhanced the cellular uptake of NPs in MDA-MB-468, an EFGR-overexpressing triple negative breast cancer (TNBC) cell line. The GE11-conjugated, GFP-siRNA-complexed NPs exhibited excellent GFP gene silencing efficiency in GFP-MDA-MB-468 TNBC cells without any significant cytotoxicity. Therefore, these studies suggest that this smart unimolecular NP could be a promising nanoplatform for targeted siRNA delivery to EFGR-overexpressing cancer cells.

Carboplatin-Complexed and cRGD-Conjugated Unimolecular Nanoparticles for Targeted Ovarian Cancer Therapy.

Platinum-based chemotherapy has been widely used to treat cancers including ovarian cancer; however, it suffers from dose-limiting toxicity. Judiciously designed drug nanocarriers can enhance the anticancer efficacy of platinum-based chemotherapy while reducing its systemic toxicity. Herein the authors report a stable and water-soluble unimolecular nanoparticle constructed from a hydrophilic multi-arm star block copolymer poly(amidoamine)-b-poly(aspartic acid)-b-poly(ethylene glycol) (PAMAM-PAsp-PEG) conjugated with both cRGD (cyclo(Arg-Gly-Asp-D-Phe-Cys) peptide and cyanine5 (Cy5) fluorescent dye as a platinum-based drug nanocarrier for targeted ovarian cancer therapy. Carboplatin is complexed to the poly(aspartic acid) inner shell via pH-responsive ion-dipole interactions between carboplatin and the carboxylate groups of poly(aspartic acid). Based on flow cytometry and confocal laser scanning microscopy analyses, cRGD-conjugated unimolecular nanoparticles exhibit much higher cellular uptake by ovarian cancer cells overexpressing αv β3 integrin than nontargeted (i.e., cRGD-lacking) ones. Carboplatin-complexed cRGD-conjugated nanoparticles also exhibit higher cytotoxicity than nontargeted nanoparticles as well as free carboplatin, while empty unimolecular nanoparticles show no cytotoxicity. These results indicate that stable unimolecular nanoparticles made of individual hydrophilic multi-arm star block copolymer molecules conjugate with tumor-targeting ligands and dyes (i.e., PAMAM-PAsp-PEG-cRGD/Cy5) are promising nanocarriers for platinum-based anticancer drugs for targeted cancer therapy.

Abstract 5379: Targeting epidermal growth factor receptor positive breast cancer using nanoparticles loaded with the anti-cancer drug aminoflavone

Abstract Breast cancer is the second leading cause of cancer-related death in American women. Triple negative breast cancers (TNBCs), which lack expression of common therapeutic targets ERα and HER2, are particularly aggressive and correlated with decreased survival. While TNBCs make up 15-20% of all breast cancer cases, they account for a disproportionately large amount of breast cancer morbidity. Recently, our group has developed a novel therapeutic approach utilizing nanoparticle technology to increase targeted delivery of chemotherapeutic agents, specifically aminoflavone (AF, NSC 686288) to a model TNBC cell line that shows exquisite sensitivity to AF. We have found that AF, a synthetic flavonoid compound, exerts growth inhibitory effects in two TNBC cell lines, MDA-MB-468 and Cal51, with IC50 values in the low nanomolar range. However, in vivo studies examining the efficacy of AF indicate dose-limiting pulmonary toxicity, creating a need for drug delivery systems that circumvent toxicity through specific targeting mechanisms. This method exploits the overexpression of epidermal growth factor receptor (EGFR) commonly associated with TNBC by utilizing a unimolecular micelle nanoparticle conjugated with an EGFR-specific peptide (GE11) formed by dendritic poly(amido amine) (PAMAM) polylactide (PLA)- polyethylene glycol (PEG) amphiphilic block copolymers. The unimolecular micelle nanoparticle was also conjugated with Cy5.5 dye to allow for visualization and detection of the particles at the cellular level. Uniform size distribution and spherical morphology of the particles was confirmed using dynamic light scattering and transmission electron microscopy. Using the EGFR-overexpressing and AF-sensitive human MDA-MB-468 TNBC cell line, we were able to show that nanoparticles containing the EGFR-specific peptide GE11 exhibited increased cellular uptake, as shown using confocal microscopy for imaging and subsequent fluorescence intensity analysis. Furthermore, flow cytometric analysis confirmed that MDA-MB-468 cells treated with GE11-containing nanoparticles exhibit increased fluorescence intensity as compared to cells treated with non-targeting particles, which were not conjugated to GE11. This data suggests that the use of GE11-conjugated unimolecular micelles is an effective means of specifically targeted drug delivery in an EGFR-overexpressing TNBC cell line. The preparation and development of these nanoparticles has established a basis for further studies involving cellular toxicity and in vivo anti-tumor action of AF loaded, EGFR-targeted nanoparticles. Citation Format: Ashley M. Brinkman, Guojun Chen, Nathan Sherer, Shaoqin Gong, Wei Xu. Targeting epidermal growth factor receptor positive breast cancer using nanoparticles loaded with the anti-cancer drug aminoflavone. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5379. doi:10.1158/1538-7445.AM2014-5379

Amphiphilic Unimolecular Nanoparticles Based on a Hyperbranched Polyacrylate Core and a PNIPAm Shell: Synthesis via ATRP and Properties

A novel amphiphilic unimolecular nanoparticle, multi-HPBPEA-g-PNIPAm, for encapsulation and release of hydrophobic guest molecules, is developed. The polymer shows core–shell architecture and is synthesized from inimer 2-((2-bromopropionyl)oxy)ethyl acrylate (BPEA) by atom transfer radical polymerization (ATRP) in three steps. The hydrophobic core (multi-HPBPEA) is composed of hyperbranched poly(2-((2-bromopropionyl)oxy)ethyl acrylate) (HPBPEA), which is synthesized by self-condensing vinyl polymerization (SCVP) of BPEA. Multi-HPBPEA-g-PNIPAm is obtained by multi-HPBPEA core initiating ATRP of N-isopropylacrylamide (NIPAm). The encapsulation behavior of the core of multi-HPBPEA-g-PNIPAm in an aqueous solution is investigated by fluorescent spectra. It is found that multi-HPBPEA-g-PNIPAm can efficiently encapsulate and release a hydrophobic drug like nifedipine.

Unimolecular Nanoparticles via Carbon‐Carbon “Click” Chemistry for All‐Polymer Nanocomposites

AbstractSummary: We report for the first time the synthesis of unimolecular polystyrene‐based nanoparticles (PS‐NPs) under normal air atmosphere by direct carbon‐carbon “click” chemistry (i.e., “self‐click” chemistry). First, statistical poly(styrene‐co‐4‐vinylbenzyl chloride) copolymers synthesized by RAFT polymerization were decorated in a facile manner with alkyne groups by reaction with potassium propiolate, providing well‐defined nanoparticle precursors (PS‐Prec). Next, individual PS‐Prec chains were collapsed irreversibly to unimolecular nanoparticles of ca. 12 nm in size by intrachain Cu(II)‐catalyzed alkyne dimerization under high‐dilution conditions, as revealed by SEC, H1‐NMR, DLS and TEM measurements. Based on predictions from a recent compressible thermodynamic model, the resulting nanoparticles could be promising materials for the development of homogeneous, miscible PS‐NPs / polycarbonate all‐polymer nanocomposites.

Ethynyl-Capped Hyperbranched Conjugated Polytriazole: Click Polymerization, Clickable Modification, and Aggregation-Enhanced Emission

Cu(I)-catalyzed azide–alkyne click polymerization, developed based on the click reaction, has become a powerful tool for the construction of functional polytriazoles with linear and hyperbranched structures. This method has, however, rarely been used for the preparation of functional hyperbranched conjugated polytriazoles (hb-CPTA). In this paper, soluble ethynyl-capped hb-CPTA with weight-averaged molecular weight of 39 500 was synthesized in high yield (84.4%) by the Cu(I)-catalyzed azide–alkyne click polymerization of tetraphenylethene containing diazide [1,2-bis(4-azidophenyl)-1,2-diphenylethene] and tetrayne [1,1,2,2-tetrakis(4-ethynylphenyl)ethane] in equal concentration. By taking advantage of the ethynyl groups on its periphery, the polymer could be efficiently postfunctionalized by azide–alkyne and thiol–yne click reactions. The polymers are thermally stable and loss 5% of their weights at temperatures higher than 340.0 °C. hb-CPTA also possesses high char yield (74.8%) at 800 °C. The polymers feature the unique characteristics of aggregation-enhanced emission. Furthermore, the PL intensities of the hb-CPTA and thiol–yne postfunctionalized polytriazoles increase linearly with water fraction in THF/water mixtures. Thanks to their rigid structures, the polymers could be fabricated into unimolecular nanoparticles with sizes of ca. 100 nm. Thus, this paper provides a powerful method to synthesize soluble ethynyl-capped hyperbranched polymers, which could be a useful platform for preparation of versatile functional polymers via postreactions.

On the Apparent SEC Molecular Weight and Polydispersity Reduction upon Intramolecular Collapse of Polydisperse Chains to Unimolecular Nanoparticles

I.P.-B. thanks CSIC for her JAE-PREDOC grant. L.B. acknowledges financial support by Basque Excellence Research Center (BERC)-Materials Physics Center. Authors gratefully acknowledge financial support from the Spanish Ministry of Science and Innovation, project MAT-22007-63681, the Basque Government, project IT-436-07, and Diputacion de Gipuzkoa, project 2011-CIEN-000085-01.

Cationic Oligofluorene‐Substituted Polyhedral Oligomeric Silsesquioxane as Light‐Harvesting Unimolecular Nanoparticle for Fluorescence Amplification in Cellular Imaging

A new bottom-up strategy is used to construct water-soluble organic/inorganic fluorescent unimolecular nanoparticles based on polyhedral oligomeric silsesquioxane (POSS) and conjugated oligoelectrolyte. Their high quantum yield, good cytocompatibility, and unique whole-cell permeability could serve as a light-harvesting energy donor to amplify the intracellular dye fluorescence for high-quality biological imaging through fluorescence resonance energy transfer (see image).