Xiaoyong Wang

Platinum complexes play an important role in contemporary cancer therapy. The rational design of modern anticancer platinum complexes is largely based on the hallmarks of cancers, such as resistance to cell death, reprogramming of energy metabolism, angiogenesis, metastasis, and immunosuppressive tumor microenvironment (TME). Platinum complexes are evolving from DNA‐targeted pure chemotherapeutics to multitarget multifunctional anticancer drugs. Diverse platinum complexes with distinct cellular or molecular targets intervene in cancerous or immune cells through different mechanisms, displaying potent anticancer activities and clinical translation potential. Multimodal platinum complexes that integrate chemotherapy, immunotherapy, photodynamic therapy (PDT), sonodynamic therapy (SDT), or radiotherapy in one molecule provide new options for precise cancer treatment via synergy. This review summarizes a variety of platinum complexes designed according to different mechanisms aiming to improve therapeutic efficacy and minimize side effects of existing platinum drugs. The information is mainly extracted from representative literature published since 2020. These complexes represent the diversified development of platinum anticancer drugs in the present era.

Platinum complexes play an important role in contemporary cancer therapy. The rational design of modern anticancer platinum complexes is largely based on the hallmarks of cancers, such as resistance to cell death, reprogramming of energy metabolism, angiogenesis, metastasis, and immunosuppressive tumor microenvironment (TME). Platinum complexes are evolving from DNA‐targeted pure chemotherapeutics to multitarget multifunctional anticancer drugs. Diverse platinum complexes with distinct cellular or molecular targets intervene in cancerous or immune cells through different mechanisms, displaying potent anticancer activities and clinical translation potential. Multimodal platinum complexes that integrate chemotherapy, immunotherapy, photodynamic therapy (PDT), sonodynamic therapy (SDT), or radiotherapy in one molecule provide new options for precise cancer treatment via synergy. This review summarizes a variety of platinum complexes designed according to different mechanisms aiming to improve therapeutic efficacy and minimize side effects of existing platinum drugs. The information is mainly extracted from representative literature published since 2020. These complexes represent the diversified development of platinum anticancer drugs in the present era.

Understanding single-cell transcriptional dynamics during cellular differentiation and transition is fundamental to developmental biology. RNA velocity serves as a valuable approach for inferring these dynamics but is constrained by its reliance on simplified splicing kinetics. As a kinetics-free alternative, pseudotime-based approaches have been developed to reconstruct cellular transitions. Nevertheless, these approaches merely estimate cell–cell transitions by biasing the edges of a nearest-neighbor graph toward mature cell states. Here, we present PseudoVelo, a computational method that infers gene expression derivatives along pseudotime as “pseudo-velocity”. Utilizing the Generalized Additive Models commonly applied in pseudotime analysis, PseudoVelo fits the expression of each gene as a function of pseudotime. Then, by employing a central difference approximation, our method directly calculates the derivative of gene expression with respect to pseudotime, thereby obtaining the pseudo-velocity for each individual cell. Evaluated on multiple developmental processes, PseudoVelo demonstrates strong performance compared to CellRank 2, effectively recovering correct cellular trajectories using diverse temporal priors and demonstrating high resilience against various data perturbations.

Modulation of mitochondrial dynamics is a viable strategy for lifespan extension. Reactive oxygen species (ROS) play key roles in aging, acting either as signaling molecules to facilitate longevity-associated processes or as stimulators of oxidative stress, exerting deleterious effects on physiological functions. The hybrid molecule MC1 is designed by integrating melatonin and catechol moieties to reconstruct mitochondrial dynamics and selectively regulate the generation of ROS. MC1 combats cell senescence under oxidative stress and DNA damage, and reprograms the mitochondrial energy metabolism by inhibiting the tricarboxylic acid cycle and glycolysis, while initiating fatty acid oxidation to increase energy production. More importantly, MC1 significantly extends the lifespan of Caenorhabditis elegans, accompanied by an improvement in muscle strength and physiological functions. The lifespan-extending effect of MC1 arises from its intervention in mitochondrial membrane fusion, the electron transport chain, and differential modulation of ROS. Regulating mitochondrial dynamics and ROS production shows great potential for longevity extension.

Immune checkpoint inhibitors (ICIs) have brought revolutionary therapeutic opportunities to advanced cancers. However, the insufficient accuracy of ICIs necessitates urgent advancements in precise targeting. Herein, leveraging the high compatibility of chiral configurations with chiral biomolecules, we constructed a pair of metal-centered chiral iridium(III) nanoparticles Δ-IrBMS8-NPs and Λ-IrBMS8-NPs featuring the BMS-8 moiety to enhance the chiral adaptability with immune checkpoint biomacromolecules while avoiding the use of nanocarriers. The resulting chiral nanoparticles demonstrate markedly distinct chirality-dependent biological activities. Specifically, Δ-IrBMS8-NPs achieve a 129-fold enhancement in tumor targeting, driven by the stereoselective recognition and binding of Δ-IrBMS8-NPs to tumor-specific PD-L1. This elevated targeting accuracy of Δ-IrBMS8-NPs with PD-L1 subsequently results in significantly enhanced anticancer immune responses in vivo, especially in activating the response to cytokine pathways in dendritic cells (DCs) and the recruitment of effector CD8⁺ T cells to remodel the tumor microenvironment. This work pioneers the discovery of nanoscale metal-centered chirality in precisely targeting immune checkpoints and highlights the pivotal role of delta configurations in enhancing anticancer immune responses, paving the way for the future rational design of effective metal-based immunotherapies.

Melanoma is a refractory skin cancer with a poor response to chemotherapy and immunotherapy. Activation of the ERK pathway drives cell proliferation, metastasis, and pain in melanoma. Platinum-paeonol complexes PAP and DPAP were synthesized to inhibit melanoma and alleviate the associated pain. DPAP showed significant antimelanoma activity in vitro and vivo. It damaged DNA and mitochondria, triggering apoptosis via the mitochondrial pathway; moreover, it inhibited the expression of p-MEK1/2 and p-ERK1/2, thereby suppressing the metastasis and angiogenesis of melanoma. Uncommonly, DPAP showed the potential to relieve cancer pain by inhibiting the expressions of p-ERK1/2 and COX-2 in nerve cells and inactivating microglia and astrocytes in the spinal cord of mice. Contrary to conventional ERK inhibitors, DPAP upregulated programmed cell death ligand 1 (PD-L1), creating a unique susceptible tumor microenvironment for immunotherapy with anti-PD-1 monoclonal antibody. The combined therapy of DPAP and anti-PD-1 antibody remarkably improved their respective antitumor efficacy.

Time-series single-cell RNA sequencing enables longitudinal tracking of biological processes, yet cellular trajectory reconstruction informed by experimental time remains challenging. Existing trajectory inference methods either perform de novo reconstruction without leveraging experimental time points, or prioritize transitions between time points while paying less attention to intra-time-point dynamics. To reconcile experimental time points with local precision, we present CellDyc, a semi-supervised learning framework that leverages experimental time-point supervision to reconstruct transcriptomic velocities and recover an intrinsic gene-embedded time. CellDyc consistently outperforms existing approaches in reconstructing cellular trajectories across development, disease, and reprogramming contexts. Biologically, CellDyc provides novel insights, such as resolving temporal heterogeneity in erythroid maturation and quantitatively demonstrating that the immunosuppressive environment delays monocyte differentiation in glioblastoma. CellDyc integrates seamlessly with downstream tools like CellRank and remains robust even when only inferred temporal information is available. Collectively, CellDyc offers a rigorous, data-driven solution for deciphering time-resolved cellular dynamics.

A retinamide–platinum complex (RP) inhibits self- and metal-induced Aβ42 aggregation, reduces the generation of ROS, prevents neuroinflammation and neuronal impairment, and relieves the Aβ42-induced neurotoxicity in the AD model organism C. elegans .