Non‐Invasive Transdermal Delivery Systems with Deep Tissue Penetrating Ability for Local ROS‐Modulating Chemotherapy

Abstract Cutaneous melanoma is the deadliest malignant skin cancer due to its poor prognosis, rapid local growth, and high metastasis. Transdermal administration for local drug delivery would be one of the most appropriate therapy regimens. However, promoting drug penetration into deep tumor tissue and maintaining the balance of redox homeostasis during the antitumor treatment to inhibit melanoma progression remains a great challenge in melanoma treatment. Herein, non‐invasive transdermal delivery systems are reported for melanoma treatment, which is composed of biocompatible hydrogel and penetrating nanocarriers. Highly penetrating nanocarriers can co‐deliver paclitaxel and coenzyme Q10 for inhibiting melanoma and reducing side effects, which are attributed to drug encapsulation, deep tissue penetration, high cellular uptake, and organelle targeting. More importantly, biocompatible hydrogels serve as nanocarriers platforms for melanoma location and transdermal delivery. This hierarchical nanoparticle‐hydrogel system achieves high‐efficiency non‐invasive transdermal delivery for inhibiting melanoma, blocking adverse effects, and restraining melanoma development.