Issue

Vol. 18 (2026)

A Hierarchical Short Microneedle-Cupping Dual-Amplified Patch Enables Accelerated, Uniform, Pain-Free Transdermal Delivery of Extracellular Vesicles

https://doi.org/10.1007/s40820-025-01853-7
Minwoo Song
School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu‑ro, Jangan‑gu, Suwon 16419, Republic of Korea
Minji Ha
School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu‑ro, Jangan‑gu, Suwon 16419, Republic of Korea
Sol Shin
School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu‑ro, Jangan‑gu, Suwon 16419, Republic of Korea
Minjin Kim
School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu‑ro, Jangan‑gu, Suwon 16419, Republic of Korea
Soyoung Son
School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu‑ro, Jangan‑gu, Suwon 16419, Republic of Korea
Jihyun Lee
School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu‑ro, Jangan‑gu, Suwon 16419, Republic of Korea
Gui Won Hwang
School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu‑ro, Jangan‑gu, Suwon 16419, Republic of Korea
Jeongyun Kim
School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu‑ro, Jangan‑gu, Suwon 16419, Republic of Korea
Van Hieu Duong
School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu‑ro, Jangan‑gu, Suwon 16419, Republic of Korea
Jae Hyung Park
School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu‑ro, Jangan‑gu, Suwon 16419, Republic of Korea
Changhyun Pang
School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu‑ro, Jangan‑gu, Suwon 16419, Republic of Korea

Corresponding Author: Changhyun Pang

chpang@skku.edu

Nano-Micro Letters, Vol. 18 (2026), Article Number: 11

Abstract

Microneedles (MNs) have been extensively investigated for transdermal delivery of large-sized drugs, including proteins, nucleic acids, and even extracellular vesicles (EVs). However, for their sufficient skin penetration, conventional MNs employ long needles (≥ 600 μm), leading to pain and skin irritation. Moreover, it is critical to stably apply MNs against complex skin surfaces for uniform nanoscale drug delivery. Herein, a dually amplified transdermal patch (MN@EV/SC) is developed as the stem cell-derived EV delivery platform by hierarchically integrating an octopus-inspired suction cup (SC) with short MNs (≤ 300 μm). While leveraging the suction effect to induce nanoscale deformation of the stratum corneum, MN@EV/SC minimizes skin damage and enhances the adhesion of MNs, allowing EV to penetrate deeper into the dermis. When MNs of various lengths are applied to mouse skin, the short MNs can elicit comparable corticosterone release to chemical adhesives, whereas long MNs induce a prompt stress response. MN@EV/SC can achieve a remarkable penetration depth (290 µm) for EV, compared to that of MN alone (111 µm). Consequently, MN@EV/SC facilitates the revitalization of fibroblasts and enhances collagen synthesis in middle-aged mice. Overall, MN@EV/SC exhibits the potential for skin regeneration by modulating the dermal microenvironment and ensuring patient comfort.


Highlights:
1 A bio-inspired dual-amplified patch (MN@EV/SC) was fabricated by integrating extracellular vesicle-loaded microneedles with a soft suction chamber for effective transdermal delivery.
2 The MN@EV/SC system achieved an exceptional penetration depth of 290 μm, while minimizing plasma corticosterone levels with short microneedles, ensuring patient comfort through pain-free application.
3 This system showed the potential for dermatological application by revitalizing dermal fibroblasts, and enhancing collagen synthesis through effective delivery of extracellular vesicles while preserving their biological functionality.

Keywords

Biomimetics Cupping Microneedle Transdermal patch Extracellular vesicles
Song, Minwoo, Minji Ha, Sol Shin, Minjin Kim, Soyoung Son, Jihyun Lee, Gui Won Hwang, Jeongyun Kim, Van Hieu Duong, Jae Hyung Park, and Changhyun Pang. 2025. “A Hierarchical Short Microneedle-Cupping Dual-Amplified Patch Enables Accelerated, Uniform, Pain-Free Transdermal Delivery of Extracellular Vesicles”. Nano-Micro Letters 18 (July):11. https://doi.org/10.1007/s40820-025-01853-7.
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