Ultrasmall Silica Nanoparticle-Intrinsic Therapeutic Solutions for Modulating the Tumor-Immune Microenvironment in Cancer

Considerable strides continue to be made in the design of nanoparticles as highly specialized therapeutics for improving treatment outcomes and overcoming limitations that may be observed with standard pharmacologic agents. Novel emerging paradigms that lead to durable response rates in combination with other classes of therapeutics are also critically needed. One promising strategy exploits the unique self-therapeutic capabilities that may be exhibited by the nanomaterials themselves, which do not require attachment of a cytotoxic drug. These capabilities are governed by the physico-chemical properties of these materials, which can disrupt signal transduction pathways, cell cross-talk or invasion, induce cell death programs, or mediate other biological properties within the melanoma tumor microenvironment (TME), thereby providing unprecedented opportunities for combating disease. We find that an ultrasmall fluorescent core-shell silica nanoparticle, Cornell prime dots (C’ dots), exhibits multiple distinctly separable intrinsic therapeutic properties, including their ability to (1) specifically induce regulated cancer cell death programs, such as the iron-dependent process, ferroptosis; (2) selectively modulate expression profiles with activation of multiple gene classes and proinflammatory cytokines, in addition to their ability to (3) directly activate immune cell populations towards an anti-tumor pro-inflammatory phenotype in syngeneic models. Our future work will continue to explore the nature/type of interactions among TME populations exposed to C' dots, probing mechanisms by which these particles engage pro-inflammatory anti-tumor and cytotoxic responses. Such information, in turn, can be used to develop novel treatment paradigms for clinical cancer care.