Drug-Loaded Liposomal Spherical Nucleic Acid as an Effective Cancer Nanovaccine
Abstract Background: Cancer nanovaccine has become a promising approach for cancer immunotherapy. The major challenge of cancer vaccines is limited efficacy caused by lack of desirable tumor specific antigens (TSA). Chemotherapeutics can trigger immunogenic cell death (ICD) and release TSAs, which initiate tumor-specific immune responses. However, ICD-triggered immune responses are usually not potent enough to eliminate the tumor cells. Herein, we developed liposomal spherical nucleic acids (SNA) that can simultaneously deliver and release doxorubicin (DOX) and CpG oligonucleotides upon biological stimuli in tumors to augment antitumor immune responses. Results: SNA nanoparticle increased DOX accumulation at the tumor tissue to induce tumor cells apoptosis and autophagy to activate both ICD-triggered and autophagy-mediated Th1-type immune responses. Meanwhile, CpG, which was co-delivered with DOX, functioned synergistically to potentiate the antitumor immune responses. These nanoparticles effectively inhibited tumor growth and extended animal survival of a mouse lymphoma model. Conclusions: This work provided a simple strategy of delivering chemotherapeutics and adjuvants to tumors to improve immunotherapeutic efficacy of nanovaccines.