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Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy

FRANCESCO MANFREDI, Jingyi Wang, Eleonora Molinari, Robin Vander Pol, Casey Lewis, Xinyi Peng, Nicola Di Trani, MARCO PACI, DANILO SETTIS, Madison Alexandra Deeson, Yongbin Liu, Andrew Badachhape, Laxman Devkota, Michael Ittmann, Mahmoud Elsayad, Dinh Chuong Nguyen, Simbarashe Jokonya, Patrick S Stayton, Corrine Ying Xuan Chua, Alessandro Grattoni

Journal of Controlled Release, Volume: 395, Start page: 115004

Swansea University Authors: FRANCESCO MANFREDI, MARCO PACI, DANILO SETTIS

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DOI (Published version): 10.1016/j.jconrel.2026.115004

Abstract

Intratumoral immunotherapy presents a promising approach for enhancing cancer treatment; however, its effectiveness is limited by heterogeneous intratumoral drug distribution and rapid drug leakage following direct injection. To address these limitations, we developed a biodegradable nanofibrous dru...

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Published in: Journal of Controlled Release
ISSN: 0168-3659 1873-4995
Published: Elsevier BV 2026
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URI: https://cronfa.swan.ac.uk/Record/cronfa72177
Abstract: Intratumoral immunotherapy presents a promising approach for enhancing cancer treatment; however, its effectiveness is limited by heterogeneous intratumoral drug distribution and rapid drug leakage following direct injection. To address these limitations, we developed a biodegradable nanofibrous drug-eluting seed (b-NDES), a reservoir-based implant designed for sustained, localized diffusive delivery of immunotherapeutics. The b-NDES reduces systemic exposure and eliminates the necessity for surgical removal through gradual biodegradation. Implant bodies were fabricated by electrospinning polymeric formulations comprising varying ratios of polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and barium sulfate to provide radiopacity. Surface modifications were implemented to adjust the porous structure, allowing for tailored drug elution rates. Comparative comprehensive evaluations of morphology, in vitro release profiles, and degradation kinetics were performed. The optimized 1:4 PCL:PLGA formulation reduced permeable porosity from 18.99 ± 1.26% to 2.74 ± 1.04%, effectively decreasing the rhodamine delivery rate from 162.58 ± 16.11 μg/h to 30.68 ± 11.60 μg/h in vitro. The 1:4 PCL:PLGA structure achieved controlled diffusive drug release profile that extended intratumoral drug persistance in a 4 T1 triple-negative breast cancer (TNBC) murine model, with negligible systemic off-target exposure. Further, long-term degradation studies showed an overall mass loss of 46.32 ± 12.01% at 6 months. When loaded with a combination of CD40 agonist antibody (α-CD40) and a STING agonist (STINGa) and paired with stereotactic radiotherapy, the b-NDES platform achieved complete tumor eradication in 60% of animals. Importantly, no systemic adverse effects were observed with the intratumoral administration of the immunotherapeutic combination via b-NDES. By providing a minimally invasive, sustained-release strategy that naturally degrades to eliminate the need for surgical removal, the b-NDES represents a versatile platform for delivering potent immunotherapeutic combinations against aggressive malignancies.
Keywords: B-NDES; Biodegradable polymers; Intratumoral delivery; Triple negative breast cancer; Immunotherapy
College: Faculty of Medicine, Health and Life Sciences
Funders: This work is supported by the Houston Methodist Research Institute, the Nancy Owens Breast Cancer Foundation (A.G. and C.C.Y.X.) the U Foundation (C.C.Y.X.), and the National Institutes of Health/National Cancer Institute grant R01CA257563 (P.S·S).
Start Page: 115004

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