Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy

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

doi:10.1016/j.jconrel.2026.115004

Journal article 43 views 7 downloads

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

PDF | Version of Record

© 2026 The Authors. This is an open access article under the CC BY-NC license.
Download (15.34MB)

Check full text

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...

Full description

Published in:	Journal of Controlled Release
ISSN:	0168-3659 1873-4995
Published:	Elsevier BV 2026
Online Access:	Check full text
URI:	https://cronfa.swan.ac.uk/Record/cronfa72177

first_indexed	2026-06-26T14:21:50Z
last_indexed	2026-06-27T05:12:00Z
id	cronfa72177
recordtype	SURis
fullrecord	<?xml version="1.0"?><rfc1807><datestamp>2026-06-26T15:24:05.8134939</datestamp><bib-version>v2</bib-version><id>72177</id><entry>2026-06-26</entry><title>Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy</title><swanseaauthors><author><sid>8d674c2fa7c650e8f9a5019984dfb61f</sid><firstname>FRANCESCO</firstname><surname>MANFREDI</surname><name>FRANCESCO MANFREDI</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>8083309c9574117c9be23bc37327e97e</sid><firstname>MARCO</firstname><surname>PACI</surname><name>MARCO PACI</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>0377fb8d8283cd86dd8ab123d298d870</sid><firstname>DANILO</firstname><surname>SETTIS</surname><name>DANILO SETTIS</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2026-06-26</date><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.</abstract><type>Journal Article</type><journal>Journal of Controlled Release</journal><volume>395</volume><journalNumber/><paginationStart>115004</paginationStart><paginationEnd/><publisher>Elsevier BV</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0168-3659</issnPrint><issnElectronic>1873-4995</issnElectronic><keywords>B-NDES; Biodegradable polymers; Intratumoral delivery; Triple negative breast cancer; Immunotherapy</keywords><publishedDay>10</publishedDay><publishedMonth>7</publishedMonth><publishedYear>2026</publishedYear><publishedDate>2026-07-10</publishedDate><doi>10.1016/j.jconrel.2026.115004</doi><url/><notes/><college>COLLEGE NANME</college><CollegeCode>COLLEGE CODE</CollegeCode><institution>Swansea University</institution><apcterm>Another institution paid the OA fee</apcterm><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).</funders><projectreference/><lastEdited>2026-06-26T15:24:05.8134939</lastEdited><Created>2026-06-26T15:14:13.5832976</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>FRANCESCO</firstname><surname>MANFREDI</surname><order>1</order></author><author><firstname>Jingyi</firstname><surname>Wang</surname><order>2</order></author><author><firstname>Eleonora</firstname><surname>Molinari</surname><order>3</order></author><author><firstname>Robin Vander</firstname><surname>Pol</surname><order>4</order></author><author><firstname>Casey</firstname><surname>Lewis</surname><order>5</order></author><author><firstname>Xinyi</firstname><surname>Peng</surname><order>6</order></author><author><firstname>Nicola Di</firstname><surname>Trani</surname><order>7</order></author><author><firstname>MARCO</firstname><surname>PACI</surname><order>8</order></author><author><firstname>DANILO</firstname><surname>SETTIS</surname><order>9</order></author><author><firstname>Madison Alexandra</firstname><surname>Deeson</surname><order>10</order></author><author><firstname>Yongbin</firstname><surname>Liu</surname><order>11</order></author><author><firstname>Andrew</firstname><surname>Badachhape</surname><order>12</order></author><author><firstname>Laxman</firstname><surname>Devkota</surname><order>13</order></author><author><firstname>Michael</firstname><surname>Ittmann</surname><order>14</order></author><author><firstname>Mahmoud</firstname><surname>Elsayad</surname><order>15</order></author><author><firstname>Dinh Chuong</firstname><surname>Nguyen</surname><order>16</order></author><author><firstname>Simbarashe</firstname><surname>Jokonya</surname><order>17</order></author><author><firstname>Patrick S</firstname><surname>Stayton</surname><order>18</order></author><author><firstname>Corrine Ying Xuan</firstname><surname>Chua</surname><order>19</order></author><author><firstname>Alessandro</firstname><surname>Grattoni</surname><order>20</order></author></authors><documents><document><filename>72177__37063__e360a3794e2543cea3d98e7ae5eff7c8.pdf</filename><originalFilename>72177.VOR.pdf</originalFilename><uploaded>2026-06-26T15:20:47.0485597</uploaded><type>Output</type><contentLength>16088202</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>© 2026 The Authors. This is an open access article under the CC BY-NC license.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language><licence>http://creativecommons.org/licenses/by-nc/4.0/</licence></document></documents><OutputDurs/></rfc1807>
spelling	2026-06-26T15:24:05.8134939 v2 72177 2026-06-26 Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy 8d674c2fa7c650e8f9a5019984dfb61f FRANCESCO MANFREDI FRANCESCO MANFREDI true false 8083309c9574117c9be23bc37327e97e MARCO PACI MARCO PACI true false 0377fb8d8283cd86dd8ab123d298d870 DANILO SETTIS DANILO SETTIS true false 2026-06-26 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. Journal Article Journal of Controlled Release 395 115004 Elsevier BV 0168-3659 1873-4995 B-NDES; Biodegradable polymers; Intratumoral delivery; Triple negative breast cancer; Immunotherapy 10 7 2026 2026-07-10 10.1016/j.jconrel.2026.115004 COLLEGE NANME COLLEGE CODE Swansea University Another institution paid the OA fee 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). 2026-06-26T15:24:05.8134939 2026-06-26T15:14:13.5832976 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science FRANCESCO MANFREDI 1 Jingyi Wang 2 Eleonora Molinari 3 Robin Vander Pol 4 Casey Lewis 5 Xinyi Peng 6 Nicola Di Trani 7 MARCO PACI 8 DANILO SETTIS 9 Madison Alexandra Deeson 10 Yongbin Liu 11 Andrew Badachhape 12 Laxman Devkota 13 Michael Ittmann 14 Mahmoud Elsayad 15 Dinh Chuong Nguyen 16 Simbarashe Jokonya 17 Patrick S Stayton 18 Corrine Ying Xuan Chua 19 Alessandro Grattoni 20 72177__37063__e360a3794e2543cea3d98e7ae5eff7c8.pdf 72177.VOR.pdf 2026-06-26T15:20:47.0485597 Output 16088202 application/pdf Version of Record true © 2026 The Authors. This is an open access article under the CC BY-NC license. true eng http://creativecommons.org/licenses/by-nc/4.0/
title	Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy
spellingShingle	Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy FRANCESCO MANFREDI MARCO PACI DANILO SETTIS
title_short	Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy
title_full	Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy
title_fullStr	Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy
title_full_unstemmed	Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy
title_sort	Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy
author_id_str_mv	8d674c2fa7c650e8f9a5019984dfb61f 8083309c9574117c9be23bc37327e97e 0377fb8d8283cd86dd8ab123d298d870
author_id_fullname_str_mv	8d674c2fa7c650e8f9a5019984dfb61f_*_FRANCESCO MANFREDI 8083309c9574117c9be23bc37327e97e__MARCO PACI 0377fb8d8283cd86dd8ab123d298d870_**_DANILO SETTIS
author	FRANCESCO MANFREDI MARCO PACI DANILO SETTIS
author2	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
format	Journal article
container_title	Journal of Controlled Release
container_volume	395
container_start_page	115004
publishDate	2026
institution	Swansea University
issn	0168-3659 1873-4995
doi_str_mv	10.1016/j.jconrel.2026.115004
publisher	Elsevier BV
college_str	Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id	facultyofmedicinehealthandlifesciences
hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id	facultyofmedicinehealthandlifesciences
hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str	1
active_str	0
description	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.
published_date	2026-07-10T06:26:31Z
_version_	1869307750781026304
score	11.110583

Biodegradable nanofibrous drug-eluting seed for sustained intratumoral immunotherapy

Similar Items