Chemo-immunotherapy is a promising model for combination treatment of cancer. Many solid tumors overexpress programmed cell death ligand (PD-L1) for immune suppression. In this study, a PD-L1 binding peptide conjugate...
A peptide/DNA nanocomplex was developed to targeted delivering chemotherapeutics and photosensitizer to cancer cells for efficient combination therapy. Chemotherapeutic drug doxorubicin (DOX) and photosensitizer 5, 10, 15, 20-tetra (1-methylpyridine-4-yl) porphyrin...
Combination therapy is extensively developed for cancer treatment in recent years due to its high efficiency. Herein, we constructed a nanocomposite based on gold nanorods (GNRs) and drug-loaded tetrahedral DNA nanostructures (TDN) for chemo-photothermal combinational therapy. Anti-tumor drug doxorubicin (DOX) was loaded via the insertion within GC base pairs of TDN. The aptamer AS1411 was attached to the apex of TDN (ATDN) to target tumor cells. The DOX-loaded DNA tetrahedron (ATDN-DOX) was compressed by the GNRs coated with PEI (GNRs@ATDN-DOX) to realize the photothermal function and lysosome escape. GNRs under the illumination of 808 nm infrared laser showed high photothermal conversion and stability due to the protection of PEI layer. The drug-loading capacity of ATDN-DOX was as high as 314 DOX molecules in per ATDN. The positive charge of PEI in GNRs@ATDN-DOX nanocomposites was utilized to achieve excellent cell penetration and induce proton sponge effect for lysosomal escape. The nanocomposites presented HeLa and 4T1 cells targeting and resulted in efficient anticancer activity.
The combined delivery of chemotherapeutics with checkpoint
inhibitors
of the PD-1/PD-L1 pathway provides a new approach for cancer treatment.
Small-molecule peptide inhibitors possess short production cycle,
low immunogenicity, and fewer side effects; however, their potential
in cancer therapy is hampered by the rapid biodegradation and a nanocarrier
is needed for efficient drug delivery. Herein, anticancer drug doxorubicin
(DOX) and PD-L1 inhibitor peptide P-12 are co-loaded by a lipid polymer
nanocomplex based on poly(lactic-co-glycolic acid)
(PLGA) and DSPE-PEG. Octaarginine (R8)-conjugated DSPE-PEG renders
the LPN efficient internalization by cancer cells. The optimal nanomedicine
LPN-30-R82K@DP shows a diameter of 125 nm and a DOX and
P-12 loading content of 5.0 and 6.2%, respectively. LPN-30-R82K@DP exhibits good physiological stability and enhanced cellular
uptake by cancer cells. It successfully induces immunogenic cell death
and PD-L1 blockade in CT26 cancer cells. The in vivo antitumor study
further suggests that co-loaded nanomedicine efficiently suppresses
CT26 tumor growth and elicits antitumor immune response. This study
manifests that lipid polymer nanocomplexes are promising drug carriers
for the efficient chemo-immunotherapy of cancer.
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