2. Academic Validation
  3. Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy

Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy

  • J Control Release. 2026 Jul 10:395:115004. doi: 10.1016/j.jconrel.2026.115004.
Francesco Manfredi 1,  Jingyi Wang 2,  Eleonora Molinari 3,  Robin Vander Pol 4,  Casey Lewis 4,  Xinyi Peng 4,  Nicola Di Trani 4,  Marco Maria Paci 1,  Danilo Settis 1,  Madison Alexandra Deeson 5,  Yongbin Liu 4,  Andrew Badachhape 6,  Laxman Devkota 6,  Michael Ittmann 7,  Mahmoud Elsayad 8,  Dinh Chuong Nguyen 9,  Simbarashe Jokonya 9,  Patrick S Stayton 9,  Corrine Ying Xuan Chua 10,  Alessandro Grattoni 11
Affiliations

Affiliations

  • 1 Center of BioNanoengineering, Houston Methodist Research Institute, Houston, TX 77030, USA; College of Engineering, Swansea University, Swansea SA1 8EN, UK.
  • 2 Center of BioNanoengineering, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Nuclear Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 3 Center of BioNanoengineering, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Mechanical and Aerospace Engineering, Polytechnic of Turin, Turin 10129, Italy.
  • 4 Center of BioNanoengineering, Houston Methodist Research Institute, Houston, TX 77030, USA.
  • 5 Center of BioNanoengineering, Houston Methodist Research Institute, Houston, TX 77030, USA; Texas A&M University Naresh K. Vashisht College of Medicine, Bryan, TX 77807, USA.
  • 6 Department of Radiology, Baylor College of Medicine, Houston, TX 77030, USA.
  • 7 Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
  • 8 Department of Pathology and Laboratory Medicine, McGovern Medical School, Houston, TX 77030, USA.
  • 9 Department of Bioengineering and Molecular Engineering & Science Institute, University of Washington, Seattle, WA, USA.
  • 10 Center of BioNanoengineering, Houston Methodist Research Institute, Houston, TX 77030, USA. Electronic address: [email protected].
  • 11 Center of BioNanoengineering, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA; Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX 77030, USA. Electronic address: [email protected].
PMID: 42128062 DOI: 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 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; Immunotherapy; Intratumoral delivery; Triple negative breast cancer.

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