Figure 6. . Systemic delivery of nanomaterial-complexed viral vectors to tumor tissue via tumor microenvironment targeting.

Hypoxia, an oxygen deprivation, occurs in tumor nests due to aberrant microcirculation and vascularization, contributing to acidic pH of tumor microenvironment. As hypoxia is a common attribute shared amongst the tumors, tumor microenvironment-targeting of viral vectors via complexation with pH-sensitive nanomaterials, such as PPCBA, can induce preferential accumulation of viral vectors in the tumor. PPCBA is protonated under acidic tumor microenvironment, which increases the surface charge of PPCBA-coated viral vector and induces cellular internalization of virus to tumor cells. In contrast, PPCBA has a low surface charge under physiological pH, which restricts internalization of viral vector into nontarget cells.