Photothermal and Acid-Responsive Fucoidan-CuS Bubble Pump Microneedles for Combined CDT/PTT/CT Treatment of Melanoma

Abstract

Transdermal cancer therapy faces great challenges in clinical practice due to the low drug transdermal efficiency and the unsatisfactory effect of monotherapy. Herein, we develop a novel bubble pump microneedle system (BPMN-CuS/DOX) by embedding sodium bicarbonate (NaHCO 3 ) into hyaluronic acid microneedles (MNs) loaded with fucoidan-based copper sulfide nanoparticles (Fuc-CuS NPs) and doxorubicin (DOX). BPMN-CuS/DOX can generate CO 2 bubbles triggered by an acidic tumor microenvironment for deep and rapid intradermal drug delivery. Fuc-CuS NPs exhibit excellent photothermal effect and Fenton-like catalytic activity, producing more reactive oxygen species (ROS) by photothermal therapy (PTT) and chemodynamic therapy (CDT), which enhances the antitumor efficacy of DOX and reduces the dosage of its chemotherapy (CT). Simultaneously, DOX increases intracellular hydrogen peroxide (H 2 O 2 ) supplementation and promotes the sustained production of ROS. BPMN-CuS/ DOX significantly inhibits melanoma both in vitro and in vivo by the combination of CDT, PTT, and CT. In short, our study significantly enhances the effectiveness of transdermal drug delivery by constructing BPMNs and provides a promising novel strategy for transdermal cancer treatment with multiple therapies.

The Necessity to Investigate In Vivo Fate of Nanoparticle-Loaded Dissolving Microneedles

“…In addition, many new types of DMNs have been developed and gained more attention. For example, gas-propelled DMNs were fabricated to improve drug transdermal efficiency, which utilizes gas as the driving force for skin permeation [ 134 ]. Moreover, to achieve transmucosal sequential delivery of multiple drugs, double-layer DMNs were developed to treat oral mucosa diseases [ 130 ].…”

The Advancing Role of Nanocomposites in Cancer Diagnosis and Treatment

“…100 The problem of low drug transdermal efficiency and poor efficacy of monotherapy was solved using PTT in combination with chemodynamic therapy (CDT) and chemotherapy (CT). The constructed BPMN-CuS/DOX system significantly 102 Also, an anticancer drug, nanocomposites of the poly(N-isopropylacrylamide) (PNIPAM) containing graphene oxide (GO), PNIPAM/GO-and PNIPAMAAM/GO-based nanogels were effectively transported to cancer cells using PNIPAM/GO-DOX through the photothermal effects of NIR irradiation. 103…”

“…The constructed BPMN-CuS/DOX system significantly inhibited melanoma. 102 Also, an anticancer drug, nanocomposites of the poly(N-isopropylacrylamide) (PNIPAM) containing graphene oxide (GO), PNIPAM/GO- and PNIPAMAAM/GO-based nanogels were effectively transported to cancer cells using PNIPAM/GO-DOX through the photothermal effects of NIR irradiation. 103 …”

Metastable FeSe2 nanosheets as a one-for-all platform for stepwise synergistic tumor therapy

“…Therefore, the utilization of comprehensive multimodal therapy to obtain sufficient antitumor activity at a low dose has been investigated, in which the PTT/CDT method has shown a higher therapeutic efficiency than monomodal CDT. [11][12][13] Although such comprehensive therapeutic strategies have shown good results, their complexity hinders the further promotion of their clinical application in this field. Therefore, it would be of great significance to fully exploit the inherent physical and chemical properties of nanomaterials to facilitate their concrete implementation in the clinic.…”