Efficient drug delivery to solid tumors remains a challenge.
HER2-positive
(HER2+) tumors are an aggressive cancer subtype with a
resistance to therapy, high risk of relapse, and poor prognosis. Although
nanomedicine technology shows obvious advantages in tumor treatment,
its potential clinical translation is still impeded by the unsatisfactory
delivery and therapeutic efficacy. In this study, a gene reprogramming
macrophage membrane-encapsulated drug-loading nanoplatform was developed
for HER2+ cancer therapy based on the co-assembly of poly
(lactic-co-glycolic acid) (PLGA) nanoparticles and engineered modified
macrophage membranes. In this nanoplatform, near-infrared (NIR) fluorescent
dye ICG or chemotherapeutic drug doxorubicin (DOX) was loaded into
the PLGA cores, and an anti-HER2 affibody was stably expressed on
the membrane of macrophages. In comparison to the nanoparticles with
conventional macrophage membrane coating, the ICG/DOX@AMNP nanoparticles
armed with anti-HER2 affibody showed excellent HER2-targeting ability
both in vitro and in vivo. Small animal imaging studies confirmed
the improved pharmacokinetics of drug delivery and specific distribution
of the ICG/DOX@AMNPs in HER2+ tumors. Mechanistically,
compared with DOX@NPs or DOX@MNPs nanoparticles, DOX@AMNPs exhibited
synergistic inhibition of HER2+ cancer cells or mice tumor
growth by inducing apoptosis and blocking the PI3K/AKT signaling pathway.
Altogether, this study proposes a promising biomimetic nanoplatform
for the efficient targeted delivery of chemotherapeutic agents to
HER2+ tumors, demonstrating its great potential for solid
tumor therapy.