Intratumoral Cancer Chemotherapy with a Carrier-Based Immunogenic Cell-Death Eliciting Platinum (IV) Agent

A carrier-based,
immunogenic cell death (ICD)-eliciting platinum­(IV)
chemotherapeutic agent was synthesized via complexation between an
axially derivatized Pt­(IV)-tocopherol and hyaluronan (HA)–tocopherol
nanocarrier. The resultant HA-Pt­(IV) complex demonstrated antiproliferative
activity and induced calreticulin translocation, an indicator of ICD,
in murine and human head and neck cancer (HNC) cells. The intratumorally
administered HA-Pt­(IV) treatments were tolerable and efficacious in
both immunocompetent and immunodeficient mice with HNC, partially
because of the direct cytotoxicity. Superior efficacy and survival
were observed in the immunocompetent group, suggesting a possible
Pt­(IV)-induced immunological response, which would only manifest in
animals with an intact immune system. Subsequent imaging of tumor
tissues demonstrated increased macrophage infiltration in the HA-Pt­(IV)-treated
tumors compared to the nontreated controls and the cisplatin-treated
tumors, suggesting favorable inflammatory activation. RNA sequencing
of HA-Pt­(IV)-treated tumors indicated that carbohydrate and vitamin
metabolisms were the most important Kyoto Encyclopedia of Genes and
Genomes pathways, and molecular function, biological process, and
cellular component were highly enriched gene ontology categories.