Multistage responsive microneedle delivery system loaded oncolytic virus for topical therapy of melanoma

TY - JOUR

T1 - Multistage responsive microneedle delivery system loaded oncolytic virus for topical therapy of melanoma

AU - Wang, Zhongjie

AU - Yan, Zewei

AU - Chen, Hanlin

AU - Wang, Yue

AU - Shi, Yingjie

AU - Jing, Yuantian

AU - Ming, Ruiqi

AU - Liu, Shujun

AU - Jin, Pengfei

AU - Wu, Guanghao

AU - Huang, Lili

N1 - Publisher Copyright: © 2026 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/

PY - 2026/5

Y1 - 2026/5

N2 - Melanoma, the most aggressive form of skin cancer, remains a formidable therapeutic challenge. While oncolytic viruses (OVs) exhibit promising antitumor potential, their efficacy is often limited by insufficient intratumoral viral replication, poor tissue penetration, and the immunosuppressive tumor microenvironment (TME). Herein, a multistage microneedle (MN-OJ) system designed to amplify both local oncolysis and systemic antitumor immunity mediated by oncolytic adenovirus (OA) in melanoma. The dissolvable MN base facilitates rapid OA delivery, inducing tumor cell lysis and subsequent release of tumor-associated antigens to prime T-cell responses. Concurrently, the degradable MN tip enables sustained release of JQ1, which enhances OA replication, modulates lactic acid levels and PD-L1 expression, thereby reprogramming the immunosuppressive TME to promote T-cell infiltration and cytotoxicity. In murine models, MN-OJ demonstrated potent inhibition of both primary and distal tumors, without systemic toxicity. This innovative platform combines immediate tumor destruction with sustained immune modulation, offering a promising clinical approach for melanoma therapy.

AB - Melanoma, the most aggressive form of skin cancer, remains a formidable therapeutic challenge. While oncolytic viruses (OVs) exhibit promising antitumor potential, their efficacy is often limited by insufficient intratumoral viral replication, poor tissue penetration, and the immunosuppressive tumor microenvironment (TME). Herein, a multistage microneedle (MN-OJ) system designed to amplify both local oncolysis and systemic antitumor immunity mediated by oncolytic adenovirus (OA) in melanoma. The dissolvable MN base facilitates rapid OA delivery, inducing tumor cell lysis and subsequent release of tumor-associated antigens to prime T-cell responses. Concurrently, the degradable MN tip enables sustained release of JQ1, which enhances OA replication, modulates lactic acid levels and PD-L1 expression, thereby reprogramming the immunosuppressive TME to promote T-cell infiltration and cytotoxicity. In murine models, MN-OJ demonstrated potent inhibition of both primary and distal tumors, without systemic toxicity. This innovative platform combines immediate tumor destruction with sustained immune modulation, offering a promising clinical approach for melanoma therapy.

KW - Immune synergism

KW - JQ1

KW - Lactate metabolism

KW - Melanoma

KW - Multistage microneedle

KW - Oncolytic viruses

KW - PD-L1

KW - Tumor microenvironment

UR - https://www.scopus.com/pages/publications/105033770969

U2 - 10.1016/j.apsb.2026.02.015

DO - 10.1016/j.apsb.2026.02.015

M3 - Article

AN - SCOPUS:105033770969

SN - 2211-3835

VL - 16

SP - 3211

EP - 3223

JO - Acta Pharmaceutica Sinica B

JF - Acta Pharmaceutica Sinica B

IS - 5

ER -