Page 12 - ebook

[E. Immunology] E-6

ROS-responsive Dual Targeted Smart Nano system Boosted

Cellular Immunity Combining Immune Cell Infiltration and

Immunogenic Cell Death Against Breast Cancer

Asmita Banstola¹, Simmyung Yook¹*

¹College of Pharmacy, Keimyung University, Daegu 42601, Korea

Despite large application of immunoadjuvant and chemotherapeutic agents, cancer immunotherapy still faces
challenges due to insufficient infiltration of the immune cells in the tumor micro-environment. Chemokine therapy

has now become a new hope to address this issue as it enhances the recruitment of immune cells in the tumor
microenvironment. To enhance therapeutic effect, ROS-responsive and PD-L1 targeted nanoparticle co-

encapsulating doxorubicin (DOX), resiquimod (R848) and chemokines (MIP-3α) also known as anti-PD-L1-DOX-
R848-MIP-3α/TKNP were constructed. The constructed TKNP showed spherical morphology with a particle size of

101 ± 1.5 nm and a surface charge of -33.3 ± 1.2 mV as measured from TEM and DLS. In both in vitro and in vivo
condition, maximum retention of nanocarrier were observed. Together the combination of DOX, R848 and MIP-3α,

anti-PD-L1-DOX-R848-MIP-3α/TKNP robust immunogenic cell death phenomenon in the tumor tissue. Furthermore,
this platform also enhanced the maturation of dendritic cells in the lymph node. Increased intratumoral infiltration
of CD4+ and CD8+ T cells, as well as enhanced level of circulating and tumor infiltrated cytokine (granzyme B,

perforin) were observed in the mice treated with anti-PD-L1-DOX-R848-MIP-3α/TKNP. Thus, combination therapy

of chemokine, immunoadjuvant and cytotoxic agents in the PD-L1 targeted and ROS-responsive nanosystem
synergized anticancer therapy.