Cancer immunotherapy is revolutionary in oncology and hematology. However, a low response rate restricts the clinical benefits of this
therapy owing to inadequate T lymphocyte infiltration and low delivery efficiency of immunotherapeutic drugs. Herein, an intelligent nanovehicle (
folic acid (FA)/1-(4-(aminomethyl) benzyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-
amine (IMDQ)-
oxaliplatin (F/IMO)@
CuS) armed with multifunctional navigation is designed for the accurate delivery of cargoes to
tumor cells and dendritic cells (DCs), respectively. The nanovehicle is based on a near infrared-responsive inorganic
CuS nanoparticles, acting as a
photosensitizer and carrier of the chemotherapeutic agent
oxaliplatin, and enters
tumor cells owing to the presence of
folic acid on the surface of
CuS upon intratumoral injection. Furthermore, a
toll-like receptor (TLR) 7/8 agonist-conjugated
polymer, anchored on the surface of
CuS, is modified with
mannose to bind with DCs in the tumor microenvironment. Upon exposure to laser irradiation, nanovehicles disassemble, releasing
oxaliplatin, to ablate
tumor cells and amplify immunogenic cell death in combination with
photothermal therapy.
Mannose-modified
polymer-TLR7/8 agonist conjugates are subsequently exposed, leading to the activation of DCs and proliferation of T cells. Collectively, these intelligent nanovehicles reduce tumor burden, exert a robust antitumor immune response, and generate long-term immune protection to prevent
tumor recurrence.