Self-assembled Pt(II) metallacycles enable precise cancer combination chemotherapy.

Combination chemotherapy, which involves the simultaneous use of multiple anticancer drugs in adequate combinations to disrupt multiple mechanisms associated with tumor growth, has shown advantages in enhanced therapeutic efficacy and lower systemic toxicity relative to monotherapy. Herein, we employed coordination-driven self-assembly to construct discrete Pt(II) metallacycles as monodisperse, modular platforms for combining camptothecin and combretastatin A4, two chemotherapy agents with a disparate mechanism of action, in precise arrangements for combination chemotherapy. Formulation of the drug-loaded metallacycles with folic acid­functionalized amphiphilic diblock copolymers furnished nanoparticles with good solubility and stability in physiological conditions. Folic acids on the surface of the nanoparticles promote their internalization into cancer cells. The intracellular reductive environment of cancer cells induces the release of the drug molecules at an exact 1:1 ratio, leading to a synergistic anticancer efficacy. In vivo studies on tumor-bearing mice demonstrated the favorable therapeutic outcome and minimal side effects of the combination chemotherapy approach based on a self-assembled metallacycle.

Supramolecular Assembly in Live Cells Mapped by Real-Time Phasor-Fluorescence Lifetime Imaging.

The complex dynamics and transience of assembly pathways in living systems complicate the understanding of these molecular to nanoscale processes. Current technologies are unable to track the molecular events leading to the onset of assembly, where real-time information is imperative to correlate their rich biology. Using a chemically designed pro-assembling molecule, we map its transformation into nanofibers and their fusion with endosomes to form hollow fiber clusters. Tracked by phasor-fluorescence lifetime imaging (phasor-FLIM) in epithelial cells (L929, A549, MDA-MB 231) and correlative light-electron microscopy and tomography (CLEM), spatiotemporal splicing of the assembly events shows time-correlated metabolic dysfunction. The biological impact begins with assembly-induced endosomal disruption that reduces glucose transport into the cells, which, in turn, stymies mitochondrial respiration.

"Zero" Intrinsic Fluorescence Sensing-Platforms Enable Ultrasensitive Whole Blood Diagnosis and In Vivo Imaging.

Abnormal physiological processes and diseases can lead to content or activity fluctuations of biocomponents in organelles and whole blood. However, precise monitoring of these abnormalities remains extremely challenging due to the insufficient sensitivity and accuracy of available fluorescence probes, which can be attributed to the background fluorescence arising from two sources, 1) biocomponent autofluorescence (BCAF) and 2) probe intrinsic fluorescence (PIF). To overcome these obstacles, we have re-engineered far-red to NIR II rhodol derivatives that possess weak BCAF interference. And a series of "zero" PIF sensing-platforms were created by systematically regulating the open-loop/spirocyclic forms. Leveraging these advancements, we devised various ultra-sensitive NIR indicators, achieving substantial fluorescence boosts (190 to 1300-fold). Among these indicators, 8-LAP demonstrated accurate tracking and quantifying of leucine aminopeptidase (LAP) in whole blood at various stages of tumor metastasis. Furthermore, coupling 8-LAP with an endoplasmic reticulum-targeting element enabled the detection of ERAP1 activity in HCT116 cells with p53 abnormalities. This delicate design of eliminating PIF provides insights into enhancing the sensitivity and accuracy of existing fluorescence probes toward the detection and imaging of biocomponents in abnormal physiological processes and diseases.

Dual-Locked Fluorescent Probes Activated by Aminopeptidase N and the Tumor Redox Environment for High-Precision Imaging of Tumor Boundaries.

Clear delineation of tumor margins is essential for accurate resection and decreased recurrence rate in the clinic. Fluorescence imaging is emerging as a promising alternative to traditional visual inspection by surgeons for intraoperative imaging. However, traditional probes lack accuracy in tumor diagnosis, making it difficult to depict tumor boundaries accurately. Herein, we proposed an offensive and defensive integration (ODI) strategy based on the "attack systems (invasive peptidase) and defense systems (reductive microenvironment)" of multi-dimensional tumor characteristics to design activatable fluorescent probes for imaging tumor boundaries precisely. Screened out from a series of ODI strategy-based probes, ANQ performed better than traditional probes based on tumor unilateral correlation by distinguishing between tumor cells and normal cells and minimizing false-positive signals from living metabolic organs. To further improve the signal-to-background ratio in vivo, derivatized FANQ, was prepared and successfully applied to distinguish orthotopic hepatocellular carcinoma tissues from adjacent tissues in mice models and clinical samples. This work highlights an innovative strategy to develop activatable probes for rapid diagnosis of tumors and high-precision imaging of tumor boundaries, providing more efficient tools for future clinical applications in intraoperative assisted resection.

A Cohort Study on Deficiency of ADA2 from China.

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

Long-term follow-up of Janus-kinase inhibitor and novel active disease biomarker in juvenile dermatomyositis.

OBJECTIVE: To evaluate the use of Janus kinase inhibitor (JAKi) in treating JDM and develop cytokine biomarkers of active disease. METHODS: This study involved a retrospective cohort study that evaluated JAKi in 101 JDM patients as well as a cross-sectional study of cytokines in 128 JDM patients and 30 controls between November 2017 and December 2021 in the Affiliated Children's Hospital of Capital Institute of Pediatrics (China). RESULTS: During the median follow-up period of 19 months, 65.5% of the patients had improved rashes, and CAT-BM scores decreased. Overall, 39.6% of JDM patients eliminated glucocorticoids. Muscle strength was improved in all patients who had abnormal muscle strength before JAKi use. Patients and parents provided positive subjective reviews of JAKi, and no serious adverse events were reported. Potential side effects of JAKi included abnormal leukopoenia (14/95) and cough (16/83), which affected over 10% of the JDM patients. In the cytokine analysis, 12/34 cytokines were significantly elevated in active JDM patients. Compared with active JDM patients with multiple phenotypes, active JDM patients with only rashes demonstrated lower cytokine levels. Anti-NXP2-positive active patients had lower cytokine levels compared with those without positive anti-NXP2 antibodies. Among all increased cytokines, IL-1RA changed most dramatically, reaching over 793 times the mean of normal values. We developed a panel composed of six cytokines to differentiate active or stable status in our cohort (area under the curve = 0.8486, P < 0.05). CONCLUSION: The preliminary evidence suggested that JAKi is a relatively safe and effective alternative for JDM patients. Cytokine profiles could well reflect the inflammatory status of JDM patients.

Polymer Chemistry in Living Cells.

The polymerization of biomolecules is a central operation in biology that connects molecular signals with proliferative and information-rich events in cells. As molecules arrange precisely across 3-D space, they create new functional capabilities such as catalysis and transport highways and exhibit new phase separation phenomena that fuel nonequilibrium dynamics in cells. Hence, the observed polymer chemistry manifests itself as a molecular basis leading to cellular phenotypes, expressed as a multitude of hierarchical structures found in cell biology. Although many milestone discoveries had accompanied the rise of the synthetic polymer era, fundamental studies were realized within a closed, pristine environment and that their behavior in a complex multicomponent system remains challenging and thus unexplored. From this perspective, there is a rich trove of undiscovered knowledge that awaits the polymer science community that can revolutionize understanding in the interactive nanoscale world of the living cell.In this Account, we discuss the strategies that have enabled synthetic polymer chemistry to be conducted within the cells (membrane inclusive) and to establish monomer design principles that offer spatiotemporal control of the polymerization. As reaction considerations such as monomer concentration, polymer growth dynamics, and reactivities are intertwined with the subcellular environment and transport processes, we first provide a chemical narrative of each major cellular compartment. The conditions within each compartment will therefore set the boundaries on the type of polymer chemistry that can be conducted. Both covalent and supramolecular polymerization concepts are explored separately in the context of scaffold design, polymerization mechanism, and activation. To facilitate transport into a localized subcellular space, we show that monomers can be reversibly modified by targeting groups or stimulus-responsive motifs that react within the specific compartment. Upon polymerization, we discuss the characterization of the resultant polymeric structures and how these phase-separated structures would impact biological processes such as cell cycle, metabolism, and apoptosis. As we begin to integrate cellular biochemistry with in situ polymer science, we identify landmark challenges and technological hurdles that, when overcome, would lead to invaluable discoveries in macromolecular therapeutics and biology.

[Association of Serine/Threonine Phosphoprotein Phosphatase 4C Expression With Prognosis of Gastric Cancer].

Objective To investigate the expression level of serine/threonine phosphoprotein phosphatase 4C(PPP4C)in gastric cancer,and analyze its relationship with prognosis and the underlying regulatory mechanism.Methods The clinical data of 104 gastric cancer patients admitted to the First Affiliated Hospital of Bengbu Medical College between January 2012 and August 2016 were collected.Immunohistochemical staining was employed to determine the expression levels of PPP4C and Ki-67 in the gastric cancer tissue.The gastric cancer cell lines BGC823 and HGC27 were cultured and transfected with the vector for PPP4C knockdown,the vector for PPP4C overexpression,and the lentiviral vector(control),respectively.The effects of PPP4C on the cell cycle and proliferation were analyzed and the possible regulatory mechanisms were explored.Results PPP4C was highly expressed in gastric cancer(P<0.001),and its expression promoted malignant progression of the tumor(all P<0.01).Univariate and Cox multivariate analysis clarified that high expression of PPP4C was an independent risk factor affecting the 5-year survival rate of gastric cancer patients(P=0.003).Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that PPP4C may be involved in the cell cycle.The correlation analysis showed that the expression of PPP4C was positively correlated with that of Ki-67 in gastric cancer(P<0.001).The up-regulation of PPP4C expression increased the proportion of tumor cells in the S phase,alleviated the G2/M phase arrest,and promoted the proliferation of gastric cancer cells and the expression of cyclin D1 and cyclin-dependent kinase 6(CDK6)(all P<0.05).The down-regulation of PPP4C decreased the proportion of gastric cancer cells in the S phase,promoted G2/M phase arrest,and inhibited cell proliferation and the expression of cyclin D1,CDK6,and p53(all P<0.05).p53 inhibitors promoted the proliferation of BGC823 and HGC27 cells in the PPP4C knockdown group(P<0.001,P<0.001),while p53 activators inhibited the proliferation of BGC823 and HGC27 cells in the PPP4C overexpression group(P<0.001,P=0.002).Conclusions PPP4C is highly expressed in gastric cancer and affects the prognosis of the patients.It may increase the proportion of gastric cancer cells in the S phase and alleviate the G2/M phase arrest by inhibiting p53 signaling,thereby promoting cell proliferation.

In Situ Assembly of Platinum(II)-Metallopeptide Nanostructures Disrupts Energy Homeostasis and Cellular Metabolism.

Nanostructure-based functions are omnipresent in nature and essential for the diversity of life. Unlike small molecules, which are often inhibitors of enzymes or biomimetics with established methods of elucidation, we show that functions of nanoscale structures in cells are complex and can implicate system-level effects such as the regulation of energy and redox homeostasis. Herein, we design a platinum(II)-containing tripeptide that assembles into intracellular fibrillar nanostructures upon molecular rearrangement in the presence of endogenous H2O2. The formed nanostructures blocked metabolic functions, including aerobic glycolysis and oxidative phosphorylation, thereby shutting down ATP production. As a consequence, ATP-dependent actin formation and glucose metabolite-dependent histone deacetylase activity are downregulated. We demonstrate that assembly-driven nanomaterials offer a rich avenue to achieve broad-spectrum bioactivities that could provide new opportunities in drug discovery.

A self-assembled Ru-Pt metallacage as a lysosome-targeting photosensitizer for 2-photon photodynamic therapy.

Photodynamic therapy (PDT) is a treatment procedure that relies on cytotoxic reactive oxygen species (ROS) generated by the light activation of a photosensitizer. The photophysical and biological properties of photosensitizers are vital for the therapeutic outcome of PDT. In this work a 2D rhomboidal metallacycle and a 3D octahedral metallacage were designed and synthesized via the coordination-driven self-assembly of a Ru(II)-based photosensitizer and complementary Pt(II)-based building blocks. The metallacage showed deep-red luminescence, a large 2-photon absorption cross-section, and highly efficient ROS generation. The metallacage was encapsulated into an amphiphilic block copolymer to form nanoparticles to encourage cell uptake and localization. Upon internalization into cells, the nanoparticles selectively accumulate in the lysosomes, a favorable location for PDT. The nanoparticles are almost nontoxic in the dark, and can efficiently destroy tumor cells via the generation of ROS in the lysosomes under 2-photon near-infrared light irradiation. The superb PDT efficacy of the metallacage-containing nanoparticles was further validated by studies on 3D multicellular spheroids (MCS) and in vivo studies on A549 tumor-bearing mice.

Rhomboidal Pt(II) metallacycle-based NIR-II theranostic nanoprobe for tumor diagnosis and image-guided therapy.

Fluorescent theranostics probes at the second near-IR region (NIR-II; 1.0-1.7 µm) are in high demand for precise theranostics that minimize autofluorescence, reduce photon scattering, and improve the penetration depth. Herein, we designed and synthesized an NIR-II theranostic nanoprobe 1 that incorporates a Pt(II) metallacycle 2 and an organic molecular dye 3 into DSPE-mPEG5000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]). This design endows 1 with good photostability and passive targeting ability. Our studies show that 1 accurately diagnoses cancer with high resolution and selectively delivers the Pt(II) metallacycle to tumor regions via an enhanced permeability and retention effect. In vivo studies reveal that 1 efficiently inhibits the growth of tumor with minimal side effects. At the same time, improved fluorescent imaging quality and signal-to-noise ratios are shown due to the long emission wavelengths. These studies demonstrate that 1 is a potential theranostic platform for tumor diagnosis and treatment in the NIR-II region.

Analysis of five cases of monogenic lupus related to primary immunodeficiency diseases.

OBJECTIVE AND DESIGN: We studied five cases of PID-related monogenic lupus to explore the characteristics. MATERIAL OR SUBJECTS: Among 42 cases of PID patients between 2017-2020, 5 patients were diagnosed as PID-related monogenic lupus, including 2 males and 3 females, with age range from 2 years 3 months to 13 years old. TREATMENTS: DMARDs, biological agents and stem cell transplantation were used to treat different patients. METHODS: We collected the clinical observation indicators, auxiliary examination and treatment of the five patients. RESULTS: Patient 1 was diagnosed with monogenic lupus secondary to severe combined immunodeficiency and received prednisone and methotrexate treatment. Patient 2 was diagnosed with monogenic lupus secondary to activated phosphoinositide 3-kinase δ syndrome. Allogeneic stem cell transplantation was conducted. Patient 3 was diagnosed with monogenic lupus secondary to RAS-associated lymphoproliferative disease. The child was treated with prednisone and rituximab. Patient 4 was diagnosed with monogenic lupus secondary to PSTPIP1-associated myeloid-related proteinaemia inflammatory syndrome. The child was given methylprednisolone, methotrexate, and infliximab. Patient 5 was diagnosed with monogenic lupus secondary to A20 haploinsufficiency. The child was treated with methylprednisolone and infliximab. CONCLUSIONS: Multiple PIDs can lead to monogenic lupus. Different PID-related monogenic lupus has different suitable targeted drugs.

Heterometallic Ru-Pt metallacycle for two-photon photodynamic therapy.

As an effective and noninvasive treatment of various diseases, photodynamic therapy (PTD) relies on the combination of light, a photosensitizer, and oxygen to generate cytotoxic reactive oxygen species that can damage malignant tissue. Much attention has been paid to covalent modifications of the photosensitizers to improve their photophysical properties and to optimize the pathway of the photosensitizers interacting with cells within the target tissue. Herein we report the design and synthesis of a supramolecular heterometallic Ru-Pt metallacycle via coordination-driven self-assembly. While inheriting the excellent photostability and two-photon absorption characteristics of the Ru(II) polypyridyl precursor, the metallacycle also exhibits red-shifted luminescence to the near-infrared region, a larger two-photon absorption cross-section, and higher singlet oxygen generation efficiency, making it an excellent candidate as a photosensitizer for PTD. Cellular studies reveal that the metallacycle selectively accumulates in mitochondria and nuclei upon internalization. As a result, singlet oxygen generated by photoexcitation of the metallacycle can efficiently trigger cell death via the simultaneous damage to mitochondrial function and intranuclear DNA. In vivo studies on tumor-bearing mice show that the metallacycle can efficiently inhibit tumor growth under a low light dose with minimal side effects. The supramolecular approach presented in this work provides a paradigm for the development of PDT agents with high efficacy.

Self-Assembly of Porphyrin-Containing Metalla-Assemblies and Cancer Photodynamic Therapy.

In this report, we describe the synthesis of two porphyrin-containing Pt(II) supramolecular assemblies via coordination-driven self-assembly. X-ray crystallographic analysis on one assembly reveals that the metalla-assembly formation imposes large interchromophore distances, leading to a higher 1O2 generation efficiency, relative to the corresponding small molecular precursors. The metalla-assemblies were examined as photosensitizers for photodynamic therapy as the potential reduction of the unfavorable self-aggregation phenomenon. In vivo and in vitro investigations demonstrate that the metalla-assemblies exhibit enhanced anticancer activity with minimal dose requirement and side effects comparable to the small molecule precursors. Thus, our work demonstrates that self-assembly provides a promising methodology for enhancing the therapeutic effectiveness of anticancer agents.

Metallacycle-cored supramolecular assemblies with tunable fluorescence including white-light emission.

Control over the fluorescence of supramolecular assemblies is crucial for the development of chemosensors and light-emitting materials. Consequently, the postsynthetic modification of supramolecular structures via host-guest interactions has emerged as an efficient strategy in recent years that allows the facile tuning of the photophysical properties without requiring a tedious chemical synthesis. Herein, we used a phenanthrene-21-crown-7 (P21C7)-based 60° diplatinum(II) acceptor 8 in the construction of three exohedral P21C7 functionalized rhomboidal metallacycles 1-3 which display orange, cyan, and green emission colors, respectively. Although these colors originate from the dipyridyl precursors 10-12, containing triphenylamine-, tetraphenylethene-, and pyrene-based fluorophores, respectively, the metal-ligand coordination strongly influences their emission properties. The metallacycles were further linked into emissive supramolecular oligomers by the addition of a fluorescent bis-ammonium linker 4 that forms complementary host-guest interactions with the pendant P21C7 units. Notably, the final ensemble derived from a 1:1 mixture of 1 and 4 displays a concentration-dependent emission. At low concentration, i.e., <25 µM, it emits a blue color, whereas an orange emission was observed when the concentration exceeds >5 mM. Moreover, white-light emission was observed from the same sample at a concentration of 29 µM, representing a pathway to construct supramolecular assemblies with tunable fluorescence properties.

Trackable Supramolecular Fusion: Cage to Cage Transformation of Tetraphenylethylene-Based Metalloassemblies.

Herein, the trackable supramolecular transformation of a two-component molecular cage to a three-component cage through supramolecular fusion with another two-component molecular square is described. The use of tetraphenylethene (TPE), a chromophore with aggregation-induced emission (AIE) character, as a component for the molecular cages enables facile fluorescence monitoring of the transformation process: while both cages exhibit fluorescence emission via the restriction of intramolecular motion of the TPE motif, the interactions between TPE and 4,4'-bipyridine introduced in the supramolecular fusion process result in partial fluorescence quenching and shifts in the emission maximum. This study provides a simple and efficient approach towards complex supramolecular cages with emergent functions and demonstrates that AIE features could provide unique opportunities for the characterization of complex, dynamic supramolecular transformation processes.

Understanding the Effects of Coordination and Self-Assembly on an Emissive Phenothiazine.

The local environment surrounding luminophores can significantly influence their photophysical properties. Herein, we report the self-assembly of a highly emissive platinum(II)-based metallacage. In order to accommodate the connectivity of the platinum(II) building block used in the self-assembly process, the luminophore-containing building block adopts a highly twisted geometry relative to its free form, leading to the emergence of an emissive transition with a radiative rate constant an order of magnitude higher than that of the free luminophore. This increased rate constant is the primary driver for the 10-fold increase in quantum yield from 4.2% to 40%. Model complexes with platinum or methyl groups bound to the nitrogen were synthesized. These complexes had lower quantum yields (10% and non-emissive, respectively) due mainly to decreases in radiative rate constants. Computational studies were conducted and indicated that the excited state of the ensembles, as well as the model complexes, is a result of charge transfer to the pyridyl groups, in contrast to the free luminophore, which involves the diphenyl sulfone moiety. The differences in quantum yields can be explained by a twist in the chromophore upon coordination of platinum or methylation on the pyridyl group, leading to intersystem crossing to a triplet state. This state then becomes more emissive with the addition of platinum, which increases the radiative rate constant via the heavy atom effect. The formation of a metallacage also decreases the non-radiative rate constant by inhibiting the intramolecular motions of the incorporated luminophore.

Spontaneous Supramolecular Polymerization Driven by Discrete Platinum Metallacycle-Based Host-Guest Complexation.

Considerable progress in platinum metallacycle-based supramolecular polymerization has promoted the fabrication and application of supramolecular materials. However, despite recent advances, supramolecular polymers constructed through platinum metallacycle-based host-guest complexation remain rare because of the dynamics of platinum metallacycles. Here, we achieve linear supramolecular polymerization via platinum metallacycle-based host-guest complexation by following the design rule of suppressing the dynamics of the metallacycles. The establishment of the platinum metallacycle-based host-guest system and the realization of this type of supramolecular polymerization are expected to open opportunities for platinum metallacycle-based functional materials.

Designed Conformation and Fluorescence Properties of Self-Assembled Phenazine-Cored Platinum(II) Metallacycles.

A series of platinum(II) metallacycles were prepared via the coordination-driven self-assembly of a phenazine-cored dipyridyl donor with a 90° Pt(II) acceptor and various dicarboxylate donors in a 1:1:2 ratio. While the metallacycles display similar absorption profiles, they exhibit a trend of blue-shifted fluorescence emission with the decrease in the bite angles between the carboxylate building blocks. Comprehensive spectroscopic and dynamic studies as well as a computational approach were conducted, revealing that the difference in the degree of constraint imposed on the excited-state planarization of the phenazine core within these metallacycles results in their distinct photophysical behaviors. As such, a small initial difference in the dicarboxylate building blocks is amplified into distinct photophysical properties of the metallacycles, which is reminiscent of the efficient functional tuning observed in natural systems. In addition to the pre-assembly approach, the photophysical properties of a metallacycle can also be modulated using a post-assembly modification to the dicarboxylate building block, suggesting another strategy for functional tuning. This research illustrated the potential of coordination-driven self-assembly for the preparation of materials with precisely tailored functionalities at the molecular level.

Spontaneous Formation of a Cross-Linked Supramolecular Polymer Both in the Solid State and in Solution, Driven by Platinum(II) Metallacycle-Based Host-Guest Interactions.

The recent progress in platinum(II) coordination-driven supramolecular polymers has had a substantial effect on the design of functional soft materials. However, the prospect of realizing polymerization induced by platinum(II) metallacycle-based host-guest interactions has received little attention until recently. Here we report the realization of supramolecular polymerization driven by platinum(II) metallacycle-based host-guest interactions both in the solid state and in solution. On the basis of the disclosed polymerization mechanism, we present a new strategy for the preparation of platinum(II) metallacycle-based supramolecular polymers.