Selpercatinib in Chinese patients with -fusion-positive non-small-cell lung cancer: updated efficacy and safety analysis from the randomized LIBRETTO-321 phase II trial.

Background: Selpercatinib is approved for the treatment of -fusion-positive non-small-cell lung cancer (NSCLC).

Objective: We present a final update on LIBRETTO-321 to enhance the understanding of long-term efficacy and safety in Chinese patients.

Design: This open-label, multicenter, phase II study included patients with advanced -altered solid tumors.

Understanding, Mimicking, and Mitigating Radiolytic Damage to Polymers in Liquid Phase Transmission Electron Microscopy.

Advances in liquid phase transmission electron microscopy (LP-TEM) have enabled the monitoring of polymer dynamics in solution at the nanoscale, but radiolytic damage during LP-TEM imaging limits its routine use in polymer science. This study focuses on understanding, mimicking, and mitigating radiolytic damage observed in functional polymers in LP-TEM. It is quantitatively demonstrated how polymer damage occurs across all conceivable (LP-)TEM environments, and the key characteristics and differences between polymer degradation in water vapor and liquid water are elucidated.

Nanogel-based nitric oxide-driven nanomotor for deep tissue penetration and enhanced tumor therapy.

Antitumor agents often lack effective penetration and accumulation to achieve high therapeutic efficacy in treating solid tumors. Nanomotor-based nanomaterials offer a potential solution to address this obstacle. Among them, nitric oxide (NO) based nanomotors have garnered attention for their potential applications in nanomedicine.

Ultrafast light-activated polymeric nanomotors.

Synthetic micro/nanomotors have been extensively exploited over the past decade to achieve active transportation. This interest is a result of their broad range of potential applications, from environmental remediation to nanomedicine. Nevertheless, it still remains a challenge to build a fast-moving biodegradable polymeric nanomotor.

Positively Charged Biodegradable Polymersomes with Structure Inherent Fluorescence as Artificial Organelles.

Polymersomes, nanosized polymeric vesicles, have attracted significant interest in the areas of artificial cells and nanomedicine. Given their size, their visualization via confocal microscopy techniques is often achieved through the physical incorporation of fluorescent dyes, which however present challenges due to potential leaching. A promising alternative is the incorporation of molecules with aggregation-induced emission (AIE) behavior that are capable of fluorescing exclusively in their assembled state.

Polymer Vesicles with Integrated Photothermal Responsiveness.

Functionalized polymer vesicles have been proven to be highly promising in biomedical applications due to their good biocompatibility, easy processability, and multifunctional responsive capacities. However, photothermal-responsive polymer vesicles triggered by near-infrared (NIR) light have not been widely reported until now. Herein, we propose a new strategy for designing NIR light-mediated photothermal polymer vesicles.

Patient-reported outcomes following selpercatinib treatment in Chinese patients with advanced fusion-positive non-small-cell lung cancer and thyroid cancer, and -mutant medullary thyroid cancer in the phase II LIBRETTO-321 trial.

Background: Patient-reported outcomes (PROs) are increasingly becoming an important part of clinical trials as they are helpful in analyzing the safety and efficacy of treatment in chronic diseases like cancer.

Objectives: We report PROs and health-related quality of life (HRQoL) with selpercatinib treatment among Chinese patients with rearranged in transfection () fusion-positive non-small-cell lung cancer (NSCLC), fusion-positive thyroid cancer (TC), and -mutant medullary TC (MTC) as an exploratory analysis of the LIBRETTO-321 trial.

Design: A total of 77 patients (47 fusion-positive NSCLC, 1 fusion-positive TC, and 29 -mutant MTC) were enrolled.

Biodegradable Grubbs-Loaded Artificial Organelles for Endosomal Ring-Closing Metathesis.

The application of transition-metal catalysts in living cells presents a promising approach to facilitate reactions that otherwise would not occur in nature. However, the usage of metal complexes is often restricted by their limited biocompatibility, toxicity, and susceptibility to inactivation and loss of activity by the cell's defensive mechanisms. This is especially relevant for ruthenium-mediated reactions, such as ring-closing metathesis.

Inherently Fluorescent Peanut-Shaped Polymersomes for Active Cargo Transportation.

Nanomotors have been extensively explored for various applications in nanomedicine, especially in cargo transportation. Motile properties enable them to deliver pharmaceutical ingredients more efficiently to the targeted site. However, it still remains a challenge to design motor systems that are therapeutically active and can also be effectively traced when taken up by cells.

Intracranial Activity of Selpercatinib in Chinese Patients With Advanced Fusion-Positive Non-Small-Cell Lung Cancer in the Phase II LIBRETTO-321 Trial.

Purpose: Selpercatinib, a highly selective, potent RET inhibitor with CNS activity, demonstrated sustained antitumor responses and intracranial activity in patients with -altered advanced non-small-cell lung cancer (NSCLC) in the global LIBRETTO-001 and Chinese LIBRETTO-321 trials. We report a prospective case series based on updated data from patients with brain metastases at baseline in LIBRETTO-321.

Materials And Methods: We included patients with advanced NSCLC and brain metastasis with a centrally confirmed // fusion.

Selpercatinib monotherapy in a Chinese patient with RET fusion/ EGFR co-mutated nonsmall cell lung cancer from the Phase II LIBRETTO-321 study: a case report.

Rearranged during transfection ( RET ) fusions and epidermal growth factor receptor ( EGFR ) mutations are potent oncogenic drivers in patients with nonsmall cell lung cancer (NSCLC), but rarely co-exist. Concurrent RET/EGFR mutations have been reported in patients with NSCLC who develop resistance to EGFR tyrosine kinase inhibitors but are even less frequent in treatment-naïve patients. Consequently, there is no standard treatment for RET/EGFR -mutated NSCLC.

Compartmentalized Intracellular Click Chemistry with Biodegradable Polymersomes.

Polymersome nanoreactors that can be employed as artificial organelles have gained much interest over the past decades. Such systems often include biological catalysts (i.e.

Efficacy and safety of selpercatinib in Chinese patients with advanced -altered thyroid cancers: results from the phase II LIBRETTO-321 study.

Background: Selpercatinib, a highly selective and potent REarranged during Transfection (RET) kinase inhibitor, is effective in advanced -altered thyroid cancer (TC). However, the efficacy and safety in Chinese patients are unknown.

Patients And Methods: In the open-label, multi-center phase II LIBRETTO-321 (NCT04280081) study, Chinese patients with advanced solid tumors harboring alterations received selpercatinib 160 mg twice daily.

Efficacy and safety of selpercatinib in Chinese patients with advanced fusion-positive non-small-cell lung cancer: a phase II clinical trial (LIBRETTO-321).

Introduction: Oncogenic alterations in occur in 1-2% of non-small-cell lung cancers (NSCLCs). The efficacy and safety of the first-in-class, highly selective, and potent RET inhibitor selpercatinib in Chinese patients with fusion-positive NSCLC remains unknown.

Methods: In this open-label, multicenter, phase II study (NCT04280081), patients with advanced -altered solid tumors received selpercatinib (160 mg orally twice daily) in a 28-day cycle.

Twin-Engine Janus Supramolecular Nanomotors with Counterbalanced Motion.

Supramolecular nanomotors were created with two types of propelling forces that were able to counterbalance each other. The particles were based on bowl-shaped polymer vesicles, or stomatocytes, assembled from the amphiphilic block copolymer poly(ethylene glycol)--polystyrene. The first method of propulsion was installed by loading the nanocavity of the stomatocytes with the enzyme catalase, which enabled the decomposition of hydrogen peroxide into water and oxygen, leading to a chemically induced motion.

Therapeutic Stomatocytes with Aggregation Induced Emission for Intracellular Delivery.

Bowl-shaped biodegradable polymersomes, or stomatocytes, have much potential as drug delivery systems, due to their intriguing properties, such as controllable size, programmable morphology, and versatile cargo encapsulation capability. In this contribution, we developed well-defined therapeutically active stomatocytes with aggregation-induced emission (AIE) features by self-assembly of biodegradable amphiphilic block copolymers, comprising poly(ethylene glycol) (PEG) and AIEgenic poly(trimethylene carbonate) (PTMC) moieties. The presence of the AIEgens endowed the as-prepared stomatocytes with intrinsic fluorescence, which was employed for imaging of cellular uptake of the particles.

Cucurbit-Like Polymersomes with Aggregation-Induced Emission Properties Show Enzyme-Mediated Motility.

Polymersomes that incorporate aggregation-induced emission (AIE) moieties are attractive inherently fluorescent nanoparticles with biomedical application potential for cell/tissue imaging and tracking, as well as phototherapeutics. An intriguing feature that has not been explored yet is their ability to adopt a range of asymmetric morphologies. Structural asymmetry allows nanoparticles to be exploited as active (motile) systems.

Biodegradable Polymersomes with Structure Inherent Fluorescence and Targeting Capacity for Enhanced Photo-Dynamic Therapy.

Biodegradable nanostructures displaying aggregation-induced emission (AIE) are desirable from a biomedical point of view, due to the advantageous features of loading capacity, emission brightness, and fluorescence stability. Herein, biodegradable polymers comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG-P(CLgTMC)), with tetraphenylethylene pyridinium-TMC (PAIE) side chains have been developed, which self-assembled into well-defined polymersomes. The resultant AIEgenic polymersomes are intrinsically fluorescent delivery vehicles.

Self-Assembly or Coassembly of Multiresponsive Histidine-Containing Elastin-Like Polypeptide Block Copolymers.

In this study a histidine containing elastin-like polypeptide (ELP) diblock copolymer is described with multiresponsive assembly behavior. Self-assembly into micelles is examined by two methods. First, the self-assembly is triggered by the addition of divalent metal ions, with Zn being the most suitable one.

Photoactivated nanomotors via aggregation induced emission for enhanced phototherapy.

Aggregation-induced emission (AIE) has, since its discovery, become a valuable tool in the field of nanoscience. AIEgenic molecules, which display highly stable fluorescence in an assembled state, have applications in various biomedical fields-including photodynamic therapy. Engineering structure-inherent, AIEgenic nanomaterials with motile properties is, however, still an unexplored frontier in the evolution of this potent technology.

Photoactivated Polymersome Nanomotors: Traversing Biological Barriers.

Synthetic nanomotors are appealing delivery vehicles for the dynamic transport of functional cargo. Their translation toward biological applications is limited owing to the use of non-degradable components. Furthermore, size has been an impediment owing to the importance of achieving nanoscale (ca.

Mimicking Cellular Compartmentalization in a Hierarchical Protocell through Spontaneous Spatial Organization.

A systemic feature of eukaryotic cells is the spatial organization of functional components through compartmentalization. Developing protocells with compartmentalized synthetic organelles is, therefore, a critical milestone toward emulating one of the core characteristics of cellular life. Here we demonstrate the bottom-up, multistep, noncovalent, assembly of rudimentary subcompartmentalized protocells through the spontaneous encapsulation of semipermeable, polymersome proto-organelles inside cell-sized coacervates.