Under US irradiation directed to the tumor regions, SPINs generate 1O2 that can (i) debulk tumor tissues, (ii) reprogram the tumor microenvironment through upregulating the expression levels of PD-L1 and indoleamine 2,3-dioxygenase (IDO), and (iii) scissor the 1O2-cleavable linkers to remotely release the immunomodulators, NLG919 and anti-PD-L1 antibody (aPD-L1). The gene discussed is IDO1; the disease is neoplasm.