Mannose and phenylboronate ester functionalized mesoporous silica nanoparticles contained in chitosan microneedles for enhancing cellular immunity and antitumor efficacy

<b>Rationale</b>: Immunotherapy has emerged as a crucial component in cancer treatment, particularly for the long-term reduction of cancer metastasis and recurrence. However, its development is hindered by limited activation of cellular immune response and suboptimal delivery of vaccine to antigen-presenting cells. <b>Methods</b>: The vaccine was encapsulated within mesoporous silica nanoparticles, followed by functionalization by mannose and phenylboronate ester (MSN-NH-DPM), which facilitates targeting antigen-presenting cells via mannose receptors and enables intracellular delivery through endosomal escape, thereby activating cellular immunity. The nanoparticles were then integrated into chitosan microneedle patches (MNs), which are engineered to deliver the nanoparticles into the skin that is abundant in immune cells, and improve the immune response through the adjuvant properties of chitosan. <b>Results</b>: The chitosan MNs incorporating MSN-NH-DPM (CTS-MN@MSN-NH-DPM) significantly activated the cellular immune response through the MHC-I pathway. The antigen-presenting cells that uptake the vaccine migrated to nearby lymph nodes, inducing systemic immunity to eliminate cancer cells. Compared with subcutaneous injection, the application of CTS-MN@MSN-NH-DPM significantly inhibited the growth of B16/OVA melanoma tumors and extended the survival time of the melanoma mouse model. <b>Conclusions</b>: The MNs with targeted and intracellular delivery represent a promising platform for various vaccines to improve the cellular immune response, thus providing a potential solution for cancer treatment.