Cancer remains one of the world's leading causes of death. However, most conventional chemotherapeutic drugs only show a narrow therapeutic window in patients because of their inability to discriminate cancer cells from healthy cells. Nanoparticle‐based therapeutics (termed nanotherapeutics) have emerged as potential solutions to mitigate many obstacles posed by these free drugs. Deep insights into knowledge of the tumor microenvironment and materials science make it possible to construct nanotherapeutics that are able to release cargoes in response to a variety of internal stimuli and external triggers. Therefore, such highly sophisticated nanosystems could help impede the premature release of toxic drugs in the blood circulation or healthy tissues, thus enhancing the safety profiles of encapsulated drugs. In this context, this review offers a comprehensive overview of several specific stimuli, including internal stimuli (e.g., pH, temperature, enzyme, redox, and H₂O₂) and external stimuli (e.g., magnetic, photo, and ultrasound). We envision that applications of these smart nanotherapeutics can benefit cancer patients and provide a good chance for clinical translation of many nanoparticle formulas.This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > Diagnostic Nanodevices Diagnostic Tools > in vitro Nanoparticle‐Based Sensing

In recent years, as an energy storage device with a fast charge and discharge speed, long cycle life, and good stability, flexible supercapacitors (SCs) have been extensively used in flexible electronic devices such as smart textiles, flexible display screens, and micro-robots. Combining the advantages of conductive materials and hydrogels, conductive polymer hydrogels have good flexibility, biocompatibility, and adjustable mechanical and electrochemical properties, which enable them to be used as electrolyte or electrode materials for flexible SCs, endowing flexible SCs with various excellent properties and meeting their various working requirements. This paper comprehensively reviews the flexible SCs based on conductive polymer hydrogels, from the design, synthesis and application aspects of conductive polymer hydrogels, the various superior functions (e.g., self-healing, high stretchability and compressibility, high toughness, electrochromic and shape memory) of flexible SCs based on conductive polymer hydrogels to different structures of flexible SCs, including fiber-shaped structures, all-in-one sandwich structures, and in-plane interdigital microstructures. Finally, we summarize the challenges faced by flexible SCs based on conductive polymer hydrogels, which provides new research directions and prospects for future development in this field.

The often immune-suppressive tumor microenvironment (TME) may hinder immune evasion and response to checkpoint blockade therapies. Pharmacological activation of the STING pathway does create an immunologically hot TME, however, systemic delivery might lead to undesired off-target inflammatory responses. Here, we generate a small panel of esterase-activatable pro-drugs based on the structure of the non-nucleotide STING agonist MSA-2 that are subsequently stably incorporated into a liposomal vesicle for intravenous administration. The pharmacokinetic properties and immune stimulatory capacity of pro-drugs delivered via liposomes (SAProsomes) are enhanced compared to the free drug form. By performing efficacy screening among the SAProsomes incorporating different pro-drugs in syngeneic mouse tumor models, we find that superior therapeutic performance relies on improved delivery to the desired tumor and lymphoid compartments. The best candidate, SAProsome-3, highly stimulates secretion of inflammatory cytokines and creates a tumoricidal immune landscape. Notably, upon application to breast cancer or melanoma mouse models, SAProsome-3 elicits durable remission of established tumors and postsurgical tumor-free survival while decreasing metastatic burden without significant systemic toxicity. In summary, our work establishes the proof of principle for a better targeted and more efficient and safe STING agonist therapy.

Ruthenium complexes with bioactive ligands are becoming promising substitutes for platinum complexes due to their precise action against various cancers. In the present study, the synthesis of three new arene Ru(II) complexes containing new carbazole-based hydrazone ligands of general formula [(η⁶-benzene)Ru(L)Cl] (1–3; L = carbazolone benzhydrazone ligands), and their anticancer properties are described. The structural characterization of the ligands and their ruthenium complexes has been realized with the aid of elemental analysis, IR, UV-vis, NMR and HR-MS techniques. The molecular structures of all three complexes have been elucidated by single crystal X-ray crystallography and reveal the existence of pseudo-octahedral geometry around the ruthenium. The in vitro cancer cell growth inhibition property of the complexes against A549 (lung carcinoma), A2780 (ovarian adenocarcinoma) and non-cancerous 16HBE (human lung bronchial epithelium) cells were examined by MTT assay. All the complexes display good cytotoxicity towards both of these types of cancer cell compared to the standard drug cisplatin, with low IC₅₀ values. Remarkably, complex 3, which contains an electron-donating substituent, induces a significant reduction of viability in A2780 cells. The inhibition capacity of the complexes towards A2780 cells proliferation was further confirmed using 5-ethynyl-2-deoxyuridine (EdU) assay via minimal DNA synthesis. The result of the acridine orange-ethidium bromide (AO-EB) fluorescent staining assay establishes that the cytotoxicity of the complexes was mediated by apoptosis in cancer cells. Furthermore, flow cytometry using Annexin V-FITC/propidium iodide (PI) double staining determines the quantitative discrimination of early apoptosis by the externalization of phosphatidylserine. In addition, cell cycle distribution indicates that the complexes block the cell cycle progression in the S-phase. The outcome of our investigation shows the promising scope and potency of tailored arene ruthenium complexes for precise cancer chemotherapy beyond platinum drugs.