Near-Infrared Light-Activatable Microneedle System for Treating Superficial Tumors by Combination of Chemotherapy and Photothermal Therapy

Abstract

Because of the aggressive and recurrent nature of cancers, repeated and multimodal treatments are often necessary. Traditional cancer therapies have a risk of serious toxicity and side effects. Hence, it is crucial to develop an alternative treatment modality that is minimally invasive, effectively treats cancers with low toxicity, and can be repeated as required. We developed a light-activatable microneedle (MN) system that can repeatedly and simultaneously provide photothermal therapy and chemotherapy to superficial tumors and exert synergistic anticancer effects. This system consists of embeddable polycaprolactone MNs containing a photosensitive nanomaterial (lanthanum hexaboride) and an anticancer drug (doxorubicin; DOX), and a dissolvable poly(vinyl alcohol)/polyvinylpyrrolidone supporting array patch. Because of this supporting array, the MNs can be completely inserted into the skin and embedded within the target tissue for locoregional cancer treatment. When exposed to near-infrared light, the embedded MN array uniformly heats the target tissue to induce a large thermal ablation area and then melts at 50 °C to release DOX in a broad area, thus destroying tumors. This light-activated heating and releasing behavior can be precisely controlled and switched on and off on demand for several cycles. We demonstrated that the MN-mediated synergistic therapy completely eradicated 4T1 tumors within 1 week after a single application of the MN and three cycles of laser treatment. No tumor recurrence and no significant body weight loss of mice were observed. Thus, the developed light-activatable MN with a unique embeddable feature offers an effective, user-friendly, and low-toxicity option for patients requiring long-term and multiple cancer treatments.

A54 peptide-mediated functionalized gold nanocages for targeted delivery of DOX as a combinational photothermal-chemotherapy for liver cancer

“…4,5 PTT utilizes heat generated from photothermal agents under near-infrared (NIR, λ=700−1,100 nm) light irradiation, 6,7 where the absorption of tissues is quite limited, to cause irreversible cellular damage and subsequent tumor destruction because cancer cells are more heat-sensitive than normal ones. 8 In PTT, photothermal agents are delivered to tumors either intravenously or intratumorally.…”

Gold nanorod–based poly(lactic-co-glycolic acid) with manganese dioxide core–shell structured multifunctional nanoplatform for cancer theranostic applications

“…3 With the development of tumor adjunctive therapy, the combined therapy of hyperthermia and chemotherapy has become a hot spot in related research fields. 4,5 Gold nanomaterials are a type of biomaterials that exhibit many excellent properties, such as easy molding, easy modification, and low toxicity, and they have always been used for near-infrared (NIR) light-induced photothermal therapy (PTT). 6,7 However, low tissue penetration and skin burning of NIR laser have seriously hindered its use.…”

Fe3O4/Polycaprolactone Microneedles with Controlled Drug Delivery and Magnetic Hyperthermia

“…For the treatment of skin cancers, microneedles are possible to arrive at tumor tissues, allowing for enhancing efficacy of therapeutic delivery. [22][23][24][25][26] For example, Wang et al reported the microneedle patch-assisted immunotherapy that delivers anti-PD-1 (aPD1) for the enhanced treatment of the skin cancer. 22 The microneedle patch with biocompatible hyaluronic acid and pH-sensitive dextran nanoparticles can painlessly penetrate the epidermis and become submerged in the interstitial fluid to efficiently deliver aPD1 to the tumor microenvironment, which inhibited tumor growth superior to those obtained with intratumor injection of the same dose.…”

“…20 Donnelly et al used silicon microneedle arrays to enhance skin penetration of porphyrin precursor 5-aminolevulinic acid (ALA) for photodynamic therapy, and in vivo experiments showed that microneedle puncture could reduce application time and ALA dose for high levels of the photosensitizer in skin. 23 Recently, Chen et al developed a multifunctional microneedle system with the combination of chemotherapy and photothermal therapy, [24][25] which consists of embeddable polycaprolactone (PCL) microneedles containing a photosensitive lanthanum hexaboride nanoparticles and an anticancer drug DOX. When applying microneedle system to treat mice bearing 4T1 breast tumors, the near-infrared light-activated heating and the DOX releasing behavior can be precisely controlled, and the microneedle-mediated synergistic therapy completely eradicated 4T1 tumors within 1 week.…”