Despite advances in photodynamic therapy (PDT) for treating superficial tumor, the prospect of this monotherapy remains challenges in the context of systemic phototoxicity and poor efficacy. In this work, a physiologically self-degradable microneedle (MN)-assisted platform is developed for combining PDT and immunotherapy via controlled co-delivery of photosensitizer (PS) and checkpoint inhibitor anti-CTLA4 antibody (aCTLA4), which generates synergistic reinforcement outcome while reducing side effects. MN is composed of biocompatible hyaluronic acid integrated with the pH-sensitive dextran nanoparticles, which is fabricated to simultaneously encapsulate hydrophobic (Zinc Phthalocyanine) and hydrophilic agents (aCTLA4) via a double emulsion method. This co-loading carrier can aggregate effectively around topical tumor by microneedle-assisted transdermal delivery. In vivo studies using 4T1 mouse models, PDT firstly exerts its effect to killing tumor and triggers the immune responses, subsequently, facilitating the immunotherapy with immune checkpoint inhibitor (aCTLA4). The possible mechanism and systemic effects of the combined therapy are investigated, which demonstrate that this co-administration platform can be a promising tool for focal cancer treatment.
Keywords: Immunotherapy; Photodynamic therapy; Polysaccharides; Systemic side effects; Transcutaneous delivery.
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