Biology subjects

Poley, M.

Publications and source records attributed to Poley, M..

3 recordsLinked to original sources

bioRxiv2025

Injectable adhesive hydrogel-drug complexes synchronize the release of chemoimmunotherapy to treat brain tumors in mice

Brain tumor therapy remains limited by an immunosuppressive, monotherapy-resistant tumor microenvironment and by a paucity of technologies capable of controlling therapy delivery kinetics to the tumor. Here, we describe tissue-adhesive hydrogel-drug complexes (HDCs) for the controlled release of combination therapies synchronized with immune cycle responses following intracranial administration. Injected adhesive HDCs enabled the controlled co-delivery of multiple payloads (chemotherapy, stimulator of interferon genes agonist cyclic dinucleotide nanoparticles, immune checkpoint blockade antibodies), leading to enhanced long-term survival (>80%) and protection from contralateral hemisphere rechallenge after a single dose in multiple syngeneic orthotopic glioblastoma mouse models. Mechanistic studies revealed that tumor rejection is a consequence of reprogramming the tumor microenvironment, driven by three key phases: the initial rapid expression of inflammatory cytokines, notably IFN-{gamma}, and tumor sensitization with antigen exposure during chemoimmunotherapy release, followed by the recruitment and subsequent sustained activation of antigen-presenting and effector cells facilitated by the hydrogels multiweek delivery period. These findings point to tissue-adhesive HDCs, and therapeutic release synchronized with biological responses as key considerations for realizing robust immune activation without provoking toxicity in the treatment of solid tumors.

bioengineering↗

bioRxiv2021

Targeting neurons in the tumor microenvironment with bupivacaine nanoparticles reduces breast cancer progression and metastases

Neurons within the tumor microenvironment promote cancer progression, thus their local targeting has potential clinical benefits. We designed PEGylated lipid nanoparticles loaded with a non-opioid analgesic, bupivacaine, to target neurons within breast cancer tumors and suppress nerve-to-cancer crosstalk. In vitro, 100-nm nanoparticles were taken up readily by primary neurons, trafficking from the neuronal body and along the axons. We demonstrate that signaling between triple-negative breast cancer cells (4T1) and neurons involves secretion of cytokines stimulating neurite outgrowth. Reciprocally, neurons stimulated 4T1 proliferation, migration and survival through secretion of neurotransmitters. Bupivacaine curbs neurite growth and signaling with cancer cells, inhibiting cancer-cell viability. In vivo, bupivacaine-loaded nanoparticles administered intravenously, suppressed neurons in orthotopic triple-negative breast cancer tumors, inhibiting tumor growth and metastatic dissemination. Overall, our findings suggest that reducing nerve involvement in tumors is important for treating cancer.

cancer biology↗

bioRxiv2020

Chemotherapeutic Nanoparticles Accumulate in the Female Reproductive System during Ovulation Affecting Fertility and Anticancer Activity

Throughout the female menstrual cycle, physiological changes occur that affect the biodistribution of nanoparticles within the reproductive system. This can have positive or negative effects. We demonstrate a 2-fold increase in nanoparticle accumulation in the ovaries during female mouse ovulation compared to the non-ovulatory stage following intravenous administration. Accumulation in the reproductive system is favored by nanoparticles smaller than 100 nm. Chemotherapeutic nanoparticles administered during ovulation increased ovarian toxicity and decreased short-term and long-term fertility when compared to the free drug. Breast cancer treated with nanomedicines during ovulation results in higher drug accumulation in the reproductive system rather than at the site of the tumor, reducing treatment efficacy. Conversely, ovarian cancer treatment was improved by enhanced nanoparticle accumulation in the ovaries during ovulation. Our findings suggest that the menstrual cycle should be considered when designing and implementing nanotherapeutics for females.

bioengineering↗