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Systemic HER3 ligand-mimicking nanobioparticles enter the brain and reduce intracranial tumour growth

Crossing the blood–brain barrier (BBB) and reaching intracranial tumours is a clinical challenge for current targeted interventions including antibody-based therapies, contributing to poor patient outcomes. Increased cell surface density of human epidermal growth factor receptor 3 (HER3) is associated with a growing number of metastatic tumour types and is observed on tumour cells that acquire resistance to a growing number of clinical targeted therapies. Here we describe the evaluation of HER3-homing nanobiological particles (nanobioparticles (NBPs)) on such tumours in preclinical models and our discovery that systemic NBPs could be found in the brain even in the absence of such tumours. Our subsequent studies described here show that HER3 is prominently associated with both mouse and human brain endothelium and with extravasation of systemic NBPs in mice and in human-derived BBB chips in contrast to non-targeted agents. In mice, systemically delivered NBPs carrying tumoricidal agents reduced the growth of intracranial triple-negative breast cancer cells, which also express HER3, with improved therapeutic profile compared to current therapies and compared to agents using traditional BBB transport routes. As HER3 associates with a growing number of metastatic tumours, the NBPs described here may offer targeted efficacy especially when such tumours localize to the brain.

Pelvic physical therapy for male sexual disorders: a narrative review

Pelvic physical therapy is an evidence-based, first-line treatment for many pelvic floor disorders and sexual dysfunction. Studies have shown that pelvic physical therapy programs can both improve pelvic floor dysfunctions and sexual function. This article aims to provide an overview of the current state of the art regarding pelvic physical therapy for male sexual dysfunction to inform healthcare providers who treat men with sexual dysfunction better. A literature review was performed in Google Scholar, PubMed, and Science Direct to find review articles, research articles, and case studies about the effect of pelvic physical therapy treatments for male sexual dysfunction. Twenty-six articles were found about various pelvic physical therapy interventions. Besides this overview of the literature, an overview of interventions used in clinical practice is also provided. This narrative review supports the potential efficacy of pelvic physical therapy in addressing male sexual dysfunction. Pelvic physical therapy approaches that comprise exercise modalities, electrotherapy approaches, manipulative techniques, lifestyle changes, behavioral suggestions, and pain management strategies, should be suggested for potential benefits in improving erectile function, premature ejaculation, and sexual dysfunction-associated chronic pelvic pain. More research is needed to examine the effect of pelvic physical therapy on hypoactive sexual desire and delayed ejaculation.

A detoxified TLR4 agonist inhibits tumour growth and lung metastasis of osteosarcoma by promoting CD8+ cytotoxic lymphocyte infiltration

Osteosarcoma is the most common malignant bone tumour with limited treatment options and poor outcomes in advanced metastatic cases. Current immunotherapies show limited efficacy, highlighting the need for novel therapeutic approaches. Systemic immune activation by Toll-like receptor 4 (TLR4) immunostimulants has shown great promise; however, current TLR4 agonists’ toxicity hinders this systemic approach in patients with osteosarcoma.

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