Bioresponsive Nanoarchitectonics-Integrated Microneedles for Amplified Chemo-Photodynamic Therapy against Acne Vulgaris

Abstract

The excessive colonization of <i>Propionibacterium acnes</i> (<i>P. acnes</i>) is responsible for the genesis of acne vulgaris, a common inflammatory disease of skin. However, the conventional anti-acne therapies are always limited by various side effects, drug resistance, and poor skin permeability. Microneedles (MNs) are emerging topical drug delivery systems capable of noninvasively breaking through the skin stratum corneum barrier to efficiently enhance the transdermal drug penetration. Herein, MNs loaded with intelligent pH-sensitive nanoplatforms were constructed for amplified chemo-photodynamic therapy against acne vulgaris, jointly exerting antimicrobial and anti-inflammatory effects. The photosensitizer indocyanine green (ICG) was loaded into the zeolitic imidazolate framework-8 (ZIF-8) to improve its photostability, which would be triggered by 808 nm laser irradiation to generate cytotoxic reactive oxygen species (ROS) to result in oxidative damage and disturbed metabolic activities of <i>P. acnes</i>. In addition to the efficient drug delivery, the ZIF-8 carrier could selectively degrade in response to the acidic microenvironment of acne lesions, and the released Zn²⁺ also exhibited a potent antimicrobial activity. The fabricated ZIF-8-ICG@MNs presented an outstanding synergistic anti-acne efficiency both <i>in vitro</i> and <i>in vivo</i>. This bioresponsive microneedle patch is expected to be readily adapted as a generalized, modular strategy for noninvasive therapeutics delivery against superficial skin diseases.