A Microneedle Patch with Self-Oxygenation and Glutathione Depletion for Repeatable Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) has attained extensive attention as a noninvasive tumor treatment modality. However, the hypoxia in solid tumors, skin phototoxicity of “always on” photosensitizers (PSs), and abundant supply of glutathione (GSH) in cancer cells severely hampered the clinical applications of PDT. Herein, a self-oxygenation nanoplatform (denoted as CZCH) with GSH depletion ability was encapsulated into the hyaluronic acid microneedle patch (MN-CZCH) to simultaneously improve the biosafety and therapeutic efficacy of PDT. The Cu2+-doped porous zeolitic imidazolate framework incorporated with catalase (CAT) is capable of efficiently loading PS 2-(1-hexyloxyethyl)-2-divinylpyropheophorbic-a (HPPH). The CZCH intermingled MN patch (MN-CZCH) could effectively penetrate the stratum corneum, topically transport HPPH to the target tumor site, achieve a long tumor retention time, and enhance the efficacy of PDT via the simultaneously synergistic effect of CAT-catalyzed self-supplying O2 and Cu2+-mediated GSH depletion. Using traceable fluorescence (FL) imaging of the released HPPH from CZCH, the FL imaging-guided repeatable PDT can be achieved for enhanced antitumor efficacy. As a result, the MN-CZCH patch exhibited excellent therapeutic efficacy against melanoma with minimal toxicity, which has promising potential for cancer theranostics.

Strategic Design of Conquering Hypoxia in Tumor for Advanced Photodynamic Therapy

“…Moreover, due to the protease‐induced degradation, instability, and immunogenicity of exogenous proteins in vivo, the tumor‐targeted delivery of exogenous proteins such as CAT is still a big challenge. [ 97 ]…”

Multifunctional MOF‐Based Microneedle Patch With Synergistic Chemo‐Photodynamic Antibacterial Effect and Sustained Release of Growth Factor for Chronic Wound Healing

“…[29,30] MNs, which comprise of hundreds of micrometer-sized projections, can circumvent the skin barrier and efficiently deliver encapsulated payloads to the body in a minimally invasive manner. [31][32][33][34][35][36] By combining their beneficial properties, MOF-MN-based drug delivery systems have been utilized for the transdermal delivery of several types of therapeutic agents in biomedical applications, such as tumor therapy [37,38] and insulin delivery. [39] Recently, MN-based formulations integrated with MOFs have also been applied for accelerating diabetes wound healing, either by delivery of metal ions for antibacterial effect or by controlled release of NO for angiogenesis in the wound.…”

Revealing drug release and diffusion behavior in skin interstitial fluid by surface-enhanced Raman scattering microneedles

“…1 They can penetrate the stratum corneum and create microporous channels to release drugs into the dermal interstitial fluid (ISF) without damaging nerves or capillaries, and have attracted increasing attention for their painless, easy self-administration, and prominent therapeutic effects. 2,3 MNs have become an emerging technology in cutting-edge biomedical fields, especially in therapy [4][5][6] and biomarker detection. [7][8][9] Dermal ISF is the first biological reservoir after the puncture of MNs into the skin.…”