Interrogating surface versus intracellular transmembrane receptor populations using cell-impermeable SNAP-tag substrates

Employing self-labelling protein tags for the attachment of fluorescent dyes has become a routine and powerful technique in optical microscopy to visualize and track fused proteins. However, membrane permeability of the dyes and the associated background signals can interfere with the analysis of extracellular labelling sites. Here we describe a novel approach to improve extracellular labelling by functionalizing the SNAP-tag substrate benzyl guanine (“BG”) with a charged sulfonate (“SBG”). This chemical manipulation can be applied to any SNAP-tag substrate, improves solubility, reduces non-specific staining and renders the bioconjugation handle impermeable while leaving its cargo untouched. We report SBG-conjugated fluorophores across the visible spectrum, which cleanly label SNAP-fused proteins in the plasma membrane of living cells. We demonstrate the utility of SBG-conjugated fluorophores to interrogate class A, B and C G protein-coupled receptors (GPCRs) using a range of imaging approaches including nanoscopic superresolution imaging, analysis of GPCR trafficking from intra- and extracellular pools, in vivo labelling in mouse brain and analysis of receptor stoichiometry using single molecule pull down.

Impermeable SNAP-tag substrates allow exclusive labelling of receptors on the cell membrane for nanoscopy, SiMPull and in vivo use.     

Palladium-catalyzed asymmetric allylic alkylation (AAA) with alkyl sulfones as nucleophiles

An efficient palladium-catalyzed AAA reaction with a simple α-sulfonyl carbon anion as nucleophiles is presented for the first time. Allyl fluorides are used as superior precursors for the generation of π-allyl complexes that upon ionization liberate fluoride anions for activation of silylated nucleophiles. With the unique bidentate diamidophosphite ligand ligated palladium as catalyst, the in situ generated α-sulfonyl carbon anion was quickly captured by the allylic intermediates, affording a series of chiral homo-allylic sulfones with high efficiency and selectivity. This work provides a mild in situ desilylation strategy to reveal nucleophilic carbon centers that could be used to overcome the pK_a limitation of “hard” nucleophiles in enantioselective transformations.

A variety of “hard” α-sulfonyl carbanions of aryl, heteroaryl and alkyl sulfones were successfully employed as nucleophiles in palladium-catalyzed asymmetric allylic alkylation with excellent enantioselectivities.     

A soft on/off switch based on the electrochemically reversible H–J interconversion of a floating porphyrin membrane

Soft molecular assemblies that respond reversibly to external stimuli are attractive materials as on/off switches, in optoelectronic, memory and sensor technologies. In this Edge Article, we present the reversible structural rearrangement of a soft porphyrin membrane under an electrical potential stimulus in the absence of solid-state architectures. The free-floating porphyrin membrane lies at the interface between immiscible aqueous and organic electrolyte solutions and is formed through interfacial self-assembly of zinc(ii) meso-tetrakis(4-carboxyphenyl)porphyrins (ZnPor). A potential difference between the two immiscible electrolyte solutions induces the intercalation of bis(triphenylphosphoranylidene)ammonium cations from the organic electrolyte that exchange with protons in the porphyrin membrane. In situ UV/vis absorbance spectroscopy shows that this ionic intercalation and exchange induces a structural interconversion of the individual porphyrin molecules in the membrane from an H- to a J-type molecular configuration. These structural rearrangements are reversible over 30 potential cycles. In situ polarisation-modulation fluorescence spectroscopy further provides clear evidence of structural interconversion of the porphyrin membrane, as intercalation of the organic electrolyte cations significantly affects the latter''s emissive properties. By adjusting the pH of the aqueous phase, additional control of the electrochemically reversible structural interconversion can be achieved, with total suppression at pH 3.

The structural rearrangement of a porphyrin membrane self-assembled at a “soft” liquid|liquid interface from a H- to J-molecular configuration is reversibly modulated by externally manipulating the interfacial Galvani potential difference.     

Activation of apoptosis by rationally constructing NIR amphiphilic AIEgens: surmounting the shackle of mitochondrial membrane potential for amplified tumor ablation

In recent years, the use of aggregation-induced emission luminogens (AIEgens) for biological imaging and phototherapy has become an area of intense research. However, most traditional AIEgens suffer from undesired aggregation in aqueous media with “always on” fluorescence, or their targeting effects cannot be maintained accurately in live cells with the microenvironment changes. These drawbacks seriously impede their application in the fields of bio-imaging and antitumor therapy, which require a high signal-to-noise ratio. Herein, we propose a molecular design strategy to tune the dispersity of AIEgens in both lipophilic and hydrophilic systems to obtain the novel near-infrared (NIR, ∼737 nm) amphiphilic AIE photosensitizer (named TPA-S-TPP) with two positive charges as well as a triplet lifetime of 11.43 μs. The synergistic effects of lipophilicity, electrostatic interaction, and structure-anchoring enable the wider dynamic range of AIEgen TPA-S-TPP for mitochondrial targeting with tolerance to the changes of mitochondrial membrane potential (ΔΨ_m). Intriguingly, TPA-S-TPP was difficult for normal cells to be taken up, indicative of low inherent toxicity for normal cells and tissues. Deeper insight into the changes of mitochondrial membrane potential and cleaved caspase 3 levels further revealed the mechanism of tumor cell apoptosis activated by AIEgen TPA-S-TPP under light irradiation. With its advantages of low dark toxicity and good biocompatibility, acting as an efficient theranostic agent, TPA-S-TPP was successfully applied to kill cancer cells and to efficiently inhibit tumor growth in mice. This study will provide a new avenue for researchers to design more ideal amphiphilic AIE photosensitizers with NIR fluorescence.

In this contribution, based on a “step-by-step” molecular design strategy, a novel NIR amphiphilic AIEgen TPA-S-TPP with a triplet lifetime of 11.43 μs and surmounting the shackle of MMP was successfully fabricated for amplified tumor ablation.     

DNAzyme- and light-induced dissipative and gated DNA networks

Nucleic acid-based dissipative, out-of-equilibrium systems are introduced as functional assemblies emulating transient dissipative biological transformations. One system involves a Pb²⁺-ion-dependent DNAzyme fuel strand-driven network leading to the transient cleavage of the fuel strand to “waste” products. Applying the Pb²⁺-ion-dependent DNAzyme to two competitive fuel strand-driven systems yields two parallel operating networks. Blocking the competitively operating networks with selective inhibitors leads, however, to gated transient operation of dictated networks, yielding gated catalytic operations. A second system introduces a “non-waste” generating out-of-equilibrium, dissipative network driven by light. The system consists of a trans-azobenzene-functionalized photoactive module that is reconfigured by light to an intermediary state consisting of cis-azobenzene units that are thermally recovered to the original trans-azobenzene-modified module. The cyclic transient photoinduced operation of the device is demonstrated. The kinetic simulation of the systems allows the prediction of the transient behavior of the networks under different auxiliary conditions.

Functional DNA modules are triggered in the presence of appropriate inhibitors to yield transient gated catalytic functions, and a photoresponsive DNA module leads to “waste-free” operation of transient, dissipative dynamic transitions.     

Diboramacrocycles: reversible borole dimerisation–dissociation systems

We report that the outcome of the tin–boron exchange reaction of a mixed thiophene-benzo-fused stannole with aryldibromoboranes is associated with the steric bulk of the aryl substituent of the borane reagent, leading to either boroles or large diboracycles as products. NMR spectroscopic studies indicate that the two products can reversibly interconvert in solution, and mechanistic density functional theory (DFT) calculations reveal boroles to be intermediates in the formation of the diboracyclic products. The addition of Lewis bases to the diboracycles leads to the corresponding borole adducts, demonstrating that they react as “masked” boroles. Additionally, the reaction of the title compounds with a series of organic azides affords complex heteropropellanes, formally 2 : 1 borole-azide adducts, that deviate from the usual BN aromatic compounds formed via nitrogen atom insertion into the boroles.

Diboramacrocycles are a new form of borole dimers, participating in various addition reactions as “masked” boroles. The reaction of a less crowded diboramacrocycle with organic azides affords unprecedented complex heteropropellanes.     

An endogenous stimulus detonated nanocluster-bomb for contrast-enhanced cancer imaging and combination therapy

Exploitation of stimuli-responsive nanoplatforms is of great value for precise and efficient cancer theranostics. Herein, an in situ activable “nanocluster-bomb” detonated by endogenous overexpressing legumain is fabricated for contrast-enhanced tumor imaging and controlled gene/drug release. By utilizing the functional peptides as bioligands, TAMRA-encircled gold nanoclusters (AuNCs) endowed with targeting, positively charged and legumain-specific domains are prepared as quenched building blocks due to the AuNCs'' nanosurface energy transfer (NSET) effect on TAMRA. Importantly, the AuNCs can shelter therapeutic cargos of DNAzyme and Dox (Dzs-Dox) to aggregate larger nanoparticles as a “nanocluster-bomb” (AuNCs/Dzs-Dox), which could be selectively internalized into cancer cells by integrin-mediated endocytosis and in turn locally hydrolyzed in the lysosome with the aid of legumain. A “bomb-like” behavior including “spark-like” appearance (fluorescence on) derived from the diminished NSET effect of AuNCs and cargo release (disaggregation) of Dzs-Dox is subsequently monitored. The results showed that the AuNC-based disaggregation manner of the “nanobomb” triggered by legumain significantly improved the imaging contrast due to the activable mechanism and the enhanced cellular uptake of AuNCs. Meanwhile, the in vitro cytotoxicity tests revealed that the detonation strategy based on AuNCs/Dzs-Dox readily achieved efficient gene/chemo combination therapy. Moreover, the super efficacy of combinational therapy was further demonstrated by treating a xenografted MDA-MB-231 tumor model in vivo. We envision that our multipronged design of theranostic “nanocluster-bomb” with endogenous stimuli-responsiveness provides a novel strategy and great promise in the application of high contrast imaging and on-demand drug delivery for precise cancer theranostics.

An in situ activable “nanocluster-bomb” detonated by endogenous overexpressing legumain is fabricated for contrast enhanced cancer imaging and effective gene/chemo-therapy.     

Design and recognition of cucurbituril-secured platinum-bound oligopeptides

Platinum terpyridyl complexes, stacked on top of one another and secured as dimers with cucurbit[8]uril (CB[8]) in aqueous medium, were functionalized quantitatively and in situ with a pair of pentapeptides Phe-(Gly)₃-Cys by grafting their cysteine residues to the Pt centers. The resulting CB[8]·(Pt·peptide)₂ assemblies were used to target secondary hosts CB[7] and CB[8] via their pair of phenylalanine residues, again in situ. A series of well-defined architectures, including a supramolecular “pendant necklace” with hybrid head-to-head and head-to-tail arrangements inside CB[8], were obtained during the self-sorting process after combining only 3 or 4 simple building units.

A platinum terpyridyl complex, pentapeptide Phe-(Gly)₃-Cys and cucurbit[8]uril assemble into a “pendant necklace” with hybrid head-to-head and head-to-tail arrangements in aqueous medium.     

An “OFF–ON–OFF” fluorescence protein-labeling probe for real-time visualization of the degradation of short-lived proteins in cellular systems

The ability to monitor proteolytic pathways that remove unwanted and damaged proteins from cells is essential for understanding the multiple processes used to maintain cellular homeostasis. In this study, we have developed a new protein-labeling probe that employs an ‘OFF–ON–OFF’ fluorescence switch to enable real-time imaging of the expression (fluorescence ON) and degradation (fluorescence OFF) of PYP-tagged protein constructs in living cells. Fluorescence switching is modulated by intramolecular contact quenching interactions in the unbound probe (fluorescence OFF) being disrupted upon binding to the PYP-tag protein, which turns fluorescence ON. Quenching is then restored when the PYP-tag–probe complex undergoes proteolytic degradation, which results in fluorescence being turned OFF. Optimization of probe structures and PYP-tag mutants has enabled this fast reacting ‘OFF–ON–OFF’ probe to be used to fluorescently image the expression and degradation of short-lived proteins.

An “OFF–ON–OFF” fluorescence probe for real-time imaging of the expression (fluorescence ‘OFF’) and degradation (fluorescence ‘ON’) of short lived PYP-tag proteins in cellular systems.     

NIR-II cell endocytosis-activated fluorescent probes for in vivo high-contrast bioimaging diagnostics

Fluorescence probes have great potential to empower bioimaging, precision clinical diagnostics and surgery. However, current probes are limited to in vivo high-contrast diagnostics, due to the substantial background interference from tissue scattering and nonspecific activation in blood and normal tissues. Here, we developed a kind of cell endocytosis-activated fluorescence (CEAF) probe, which consists of a hydrophilic polymer unit and an acid pH-sensitive small-molecule fluorescent moiety that operates in the “tissue-transparent” second near-infrared (NIR-II) window. The CEAF probe stably presents in the form of quenched nanoaggregates in water and blood, and can be selectively activated and retained in lysosomes through cell endocytosis, driven by a synergetic mechanism of disaggregation and protonation. In vivo imaging of tumor and inflammation with a passive-targeting and affinity-tagged CEAF probe, respectively, yields highly specific signals with target-to-background ratios over 15 and prolonged observation time up to 35 hours, enabling positive implications for surgical, diagnostic and fundamental biomedical studies.

A Cell Endocytosis-Activated Fluorescent (CEAF) probe triggered by disaggregation and protonation is designed for high contrast in vivo bioimaging and diagnostics in the second near-infrared window (1000–1700 nm).     

Non-metal with metal behavior: metal-free coordination-insertion ring-opening polymerization

The “coordination-insertion” ring-opening polymerization (ROP) mechanism has so far been the monopoly of metal catalysts. In this work, we present a metal-free “coordination-insertion” ROP of trimethylene carbonate (TMC) and ε-caprolactone (ε-CL), as well as their sequential block copolymerization, with N-trimethylsilyl-bis (trifluoromethanesulfonyl)imide (TMSNTf₂) as the non-metallic initiator/catalyst. TMSNTf₂ was proposed to work through an unprecedented metal-free “coordination-insertion” mechanism, which involves the coordination of monomer to the Si atom of TMSNTf₂, the nucleophilic attack of the –NTf₂ group on the coordinated monomer, and the cleavage of the acyl–oxygen bond of the monomer. The proposed metal-free “coordination-insertion” ROP was studied by NMR, SEC, and MALDI-TOF analyses. In addition, the TMSNTf₂-mediated ROP of TMC and ε-CL led to linear and cyclic polymers following two-stage first-order polymerization processes, as evidenced by structural analyses and kinetics study, which further demonstrated the metal-free “coordination-insertion” mechanism.

The first metal-free “coordination-insertion” ROP of cyclic carbonate and lactones mediated by N-trimethylsilyl-bis(trifluoromethanesulfonyl)imide (TMSNTf₂) was proposed, which in the past was exclusively the monopoly of metal complex catalysts.     

A homogeneous high-DAR antibody–drug conjugate platform combining THIOMAB antibodies and XTEN polypeptides

The antibody–drug conjugate (ADC) is a well-validated modality for the cell-specific delivery of small molecules with impact expanding rapidly beyond their originally-intended purpose of treating cancer. However, antibody-mediated delivery (AMD) remains inefficient, limiting its applicability to targeting highly potent payloads to cells with high antigen expression. Maximizing the number of payloads delivered per antibody is one key way in which delivery efficiency can be improved, although this has been challenging to carry out; with few exceptions, increasing the drug-to-antibody ratio (DAR) above ∼4 typically destroys the biophysical properties and in vivo efficacy for ADCs. Herein, we describe the development of a novel bioconjugation platform combining cysteine-engineered (THIOMAB) antibodies and recombinant XTEN polypeptides for the unprecedented generation of homogeneous, stable “TXCs” with DAR of up to 18. Across three different bioactive payloads, we demonstrated improved AMD to tumors and Staphylococcus aureus bacteria for high-DAR TXCs relative to conventional low-DAR ADCs.

Efficiency of targeted cell delivery of small molecules was enhanced in cells and animals via a novel well-defined bioconjugation platform combining site-specific antibody conjugation and XTEN polypeptides to enable high payload loading.     

SiRNA-templated 3D framework nucleic acids for chemotactic recognition,and programmable and visualized precise delivery for synergistic cancer therapy

Developments in framework nucleic acids (FNAs) are limited by complicated synthesis, by-product interference, and low framework utilization. Herein, simple core–shell spherical 3D FNAs (ST-SFNAs) preparation is presented based on siRNA-templated linear polymerization followed by hybridization chain reaction branched polymerization. Without by-products, all components exhibited their special functions to obtain high space utilization of ST-SFNAs. ST-SFNAs were covered by catalase and folic acid-functionalized liposome membranes. The catalase endowed ST-SFNAs with chemotactic activities in the H₂O₂ reaction catalyzed by catalase. Furthermore, combined with functionalized folic acids'' targeting folate receptors, the synergistic chemotactic recognition of cancer cells was obtained. This dramatically promoted targeted cellular uptakes compared with traditional active or passive targeting pathways. Subsequently, the cascaded-logical programmable release of drugs was precisely controlled by targeting glutathione and ATP (via S–S bond and ATP aptamer on the inner g-DNA cover). This was visualized by “turn on” fluorescent signals generated by special hybridization of released hairpin DNAs with survivin mRNA biomarkers. Simultaneously, biocompatible synergistic therapy was achieved by simultaneously releasing doxorubicin and siRNA. With its high utilization for synergistic chemotactic recognition, programmable and visualized delivery, as well as synergistic therapy, an efficient platform for maximizing the therapeutic efficacy has been developed. This would initiate further FNA-based material development for a variety of biological applications.

ST-SFNAs were developed by siRNA-templated linear-branched polymerizations with high space utilizations for loadings, which obtained synergistic cancer therapy via chemotactic recognition, visualized delivery, and cascaded-logical controlled release.     

Free three-dimensional carborane carbanions

Carbon atom functionalization via generation of carbanions is the cornerstone of carborane chemistry. In this work, we report the synthesis and structural characterization of free ortho-carboranyl [C₂B₁₀H₁₁]⁻, a three-dimensional inorganic analog of the elusive phenyl anion that features a “naked” carbanion center. The first example of a stable, discrete C(H)-deprotonated carborane anion was isolated as a completely separated ion pair with a crown ether-encapsulated potassium cation. An analogous approach led to the isolation and structural characterization of a doubly deprotonated 1,1′-bis(o-carborane) anion [C₂B₁₀H₁₀]₂²⁻, which is the first example of a discrete molecular dicarbanion. These reactive carbanions are key intermediates in carbon vertex chemistry of carborane clusters.

Free three-dimensional carborane carbanions, which are inorganic siblings of deprotonated aryls with the “naked” anionic carbon atom are reported.     

A highly stable RNA aptamer probe for the retinoblastoma protein in live cells

Although RNA aptamers can show comparable or better specificity and affinity to antibodies and have the advantage of being able to access different live cell compartments, they are often much less stable in vivo. We report here the first aptamer that binds human retinoblastoma protein (RB) and is stable in live cells. RB is both a key protein in cell cycle control and also a tumour suppressor. The aptamer was selected from an RNA library against a unique 12-residue helical peptide derived from RB rather than the whole protein molecule. It binds RB with high affinity (K_d = 5.1 ± 0.1 nM) and is a putative RNA G-quadruplex structure formed by an 18-nucleotide sequence (18E16 - GGA GGG UGG AGG GAA GGG), which may account for its high stability. Confocal fluorescence microscopy of live cells transfected with the aptamer shows it is stable intracellularly and efficient in entering the nucleus where an analogous antibody was inaccessible. The findings demonstrate this aptamer is an advanced probe for RB in live cell applications.

An RNA G-quadruplex aptamer, specific for the human retinoblastoma protein (RB) and highly stable inside cells, is selected and its application to live cell probing of the protein illustrated.     

Ex vivo identification of circulating tumor cells in peripheral blood by fluorometric “turn on” aptamer nanoparticles

The detection of the circulating tumor cells (CTCs) detached from solid tumors has emerged as a burgeoning topic for cancer diagnosis and treatment. The conventional CTC enrichment and identification mainly rely on the specific binding of the antibodies on the capture interface of the magnetic nanoparticles with the corresponding biomarkers on the cell membranes. However, these methods could easily generate false-negative results due to the extremely low concentration of CTCs and the internal heterogeneity of the tumor cells. Herein, with the aim of selectively identifying CTCs and improving the detection accuracy in peripheral blood, we designed the fluorometric “turn on” Au nanoparticles (DHANs) with the modification of a tumor-targeted moiety, dehydroascorbic acid (DHA) and a fluorometric aptamer, which could be “switched-on” by an over-expressed intracellular protein, namely hypoxia-inducible factor-1α (HIF 1α). This novel nanoformulated detection platform demonstrated the great capacity for visualizing various CTCs in peripheral blood with significantly improved detection efficiency and sensitivity. As a result, the nanoplatform has a great potential to be further applied for CTC detection in vitro or in vivo, which holds promise for extensive CTC studies.

The detection of the circulating tumor cells (CTCs) detached from solid tumors has emerged as a burgeoning topic for cancer diagnosis and treatment.     

Density functionals with asymptotic-potential corrections are required for the simulation of spectroscopic properties of materials

Five effects of correction of the asymptotic potential error in density functionals are identified that significantly improve calculated properties of molecular excited states involving charge-transfer character. Newly developed materials-science computational methods are used to demonstrate how these effects manifest in materials spectroscopy. Connection is made considering chlorophyll-a as a paradigm for molecular spectroscopy, 22 iconic materials as paradigms for 3D materials spectroscopy, and the V_N⁻ defect in hexagonal boron nitride as an example of the spectroscopy of defects in 2D materials pertaining to nanophotonics. Defects can equally be thought of as being “molecular” and “materials” in nature and hence bridge the relms of molecular and materials spectroscopies. It is concluded that the density functional HSE06, currently considered as the standard for accurate calculations of materials spectroscopy, should be replaced, in most instances, by the computationally similar but asymptotically corrected CAM-B3LYP functional, with some specific functionals for materials-use only providing further improvements.

Spectroscopic transitions in materials that involve charge transfer require asymptotically corrected density functionals. As most transitions do have some charge transfer character, use of such methods are generally warranted.     

Peptoid-based reprogrammable template for cell-permeable inhibitors of protein–protein interactions

The development of inhibitors of intracellular protein–protein interactions (PPIs) is of great significance for drug discovery, but the generation of a cell-permeable molecule with high affinity to protein is challenging. Oligo(N-substituted glycines) (oligo-NSGs), referred to as peptoids, are attractive as potential intracellular PPI inhibitors owing to their high membrane permeability. However, their intrinsically flexible backbones make the rational design of inhibitors difficult. Here, we propose a peptoid-based rational approach to develop cell-permeable PPI inhibitors using oligo(N-substituted alanines) (oligo-NSAs). The rigid structures of oligo-NSAs enable independent optimization of each N-substituent to improve binding affinity and membrane permeability, while preserving the backbone shape. A molecule with optimized N-substituents inhibited a target PPI in cells, which demonstrated the utility of oligo-NSA as a reprogrammable template to develop intracellular PPI inhibitors.

A peptoid-based modular approach using oligo(N-substituted alanine) as a reprogrammable template enables independent optimization of N-substituents and facile development of cell-permeable inhibitors of protein–protein interactions.     

Reusable Co-nanoparticles for general and selective N-alkylation of amines and ammonia with alcohols

A general cobalt-catalyzed N-alkylation of amines with alcohols by borrowing hydrogen methodology to prepare different kinds of amines is reported. The optimal catalyst for this transformation is prepared by pyrolysis of a specific templated material, which is generated in situ by mixing cobalt salts, nitrogen ligands and colloidal silica, and subsequent removal of silica. Applying this novel Co-nanoparticle-based material, >100 primary, secondary, and tertiary amines including N-methylamines and selected drug molecules were conveniently prepared starting from inexpensive and easily accessible alcohols and amines or ammonia.

A general cobalt-catalyzed N-alkylation of amines with alcohols by borrowing hydrogen methodology to prepare different kinds of amines is reported.     

A dendritic cell-like biomimetic nanoparticle enhances T cell activation for breast cancer immunotherapy

Cancer immunotherapy has remarkably improved the therapeutic effect of melanoma and non-small cell lung cancer in the clinic. Nevertheless, it showed disappointing clinical outcomes for treating immunosuppressive tumors, wherein aggressive T cells are rather limited in tumor sites. Therefore, regulating the behavior of T cells in tumor sites to increase their attack ability for suppressing the immunosuppressive tumor is highly desirable. Inspiringly, we designed a dendritic cell-like biomimetic nanoparticle (DMSNs³@HA) to regulate the behavior of T cells for improving the immunotherapy effect against immunosuppressive tumors. In this work, anti-CD3 and anti-CD28 were responsible for mimicking dendritic cells to activate T cells, and anti-PD-1 for blocking the pathway of PD-1/PD-L1 to break the immune “brake”, which synergistically regulated the behavior of T cells to attack cancer cells. Experimental results indicated that DMSNs³@HA can effectively activate T cells and improve their immune response to significantly inhibit the growth of breast cancer. Moreover, it also proved that T cell activation combining immune checkpoint blocking induced the “1 + 1 >2” immunotherapy effect against immunosuppressive tumors. We expect that this strategy will provide new insights into tumor immunotherapy by modulating T cell behavior.

A dendritic cell-like biomimetic nanoparticle has been designed to regulate the behavior of T cells for improving the immunotherapy effect against immunosuppressive tumors.