Herein, we proposed novel separable cryo-microneedles patches delivered with capsaicin integrated mesoporous dopamine (mPDA) for obesity treatment through activating transient receptor potential vanilloid-1 (TRPV1) and inducing lipid droplet dissolution, as outlined in Fig. 1. The gene discussed is TRPV1; the disease is obesity due to melanocortin 4 receptor deficiency.