Highly Efficient Near‐IR Photothermal Microneedles with Flame‐Made Plasmonic Nanoaggregates for Reduced Intradermal Nanoparticle Deposition

Abstract

PTT, nanoparticles (NPs) can be used to convert electromagnetic radiation to heat. Increasing the local temperature in the skin may improve the therapeutic outcome of various diseases, such as skin tumors and cancer, or bacterial, parasitic, and viral skin infections. [1] Target temperatures for PTT often range from 38 to 55 °C with a heating above ≈50 °C causing protein denaturation and tissue coagulation which may interfere with successful therapy. [4] The therapeutic effect of hyperthermia is to i) induce cellular apoptosis and necrosis in cells, ii) increase the blood flow, and iii) elicit immune responses. [1,4] Furthermore, combining hyperthermia with pharmaceutical treatments may reduce the required drug dose, which is specifically relevant for the prevention of further development of drug resistance. [5] For successful application of PTT in dermatological conditions, it is required that the heat is evenly distributed into potentially deep layers of the skin. [6] Microneedle (MN) arrays have been extensively studied in recent years for PTT-based skin therapy [7,8] and the photothermal agents that have been delivered via MNs include silica-coated lanthanum hexaboride, [9][10][11] gold nanorods [6,12,13] and nanocages, [14] Prussian blue NPs, [15] graphene oxide NPs, [16,17] black phosphorus quantum dots, [18] indocyanine green, [19][20][21] CuO 2 NPs, [22] and Nb 2 C nanosheets. [23] In all those examples, the photothermal agent is active in the near-infrared (NIR) wavelength region which avoids nonspecific thermal damage to tissue. [24] Importantly, MN-assisted delivery of PTT can enhance treatment outcomes in cancers and reduce bacterial infections while distributing the hyperthermia evenly and deep into the skin. [8] However, the broad employment of photothermal MN arrays is prohibited due to high production costs of some photothermal agents (e.g., gold nanorods), their poor long-term stability, and/or degradation by photobleaching (e.g., indocyanine green). [5,25] The lack of high photothermal efficiency of some proposed PTT-based MNs systems also requires high laser intensities up to 5 W cm −2 . [9,13,26] Such high laser intensities may limit clinical translation of MN arrays for PTT since laser intensities above 0.3-1.0 W cm −2 at 780-1050 nm are the maximum permissible exposure limit to skin according to the American National Standard for Safe Use of Lasers. [27] Furthermore, Near-infrared (NIR) photothermal therapy by microneedles (MNs) exhibits high potential against skin diseases. However, high costs, photobleaching of organic agents, low long-term stability, and potential nanotoxicity limit the clinical translation of photothermal MNs. Here, photothermal MNs are developed by utilizing Au nanoaggregates made by flame aerosol technology and incorporated in water-insoluble polymer matrix to reduce intradermal nanoparticle (NP) deposition. The individual Au interparticle distance and plasmonic coupling within the nanoaggregates are controlled by the addition of a spacer during their synthesis renderi...