Liposomal Co-delivery of PD-L1 siRNA/Anemoside B4 for Enhanced Combinational Immunotherapeutic Effect

Abstract

Combination therapy has gained a lot of attention thanks to its superior activity against cancer. In the present study, we report a cRGDtargeted liposomal preparation for co-delivery of programmed cell death ligand 1 (PD-L1) small interfering RNA (siRNA) and anemoside B4 (AB4)AB4/siP-c-Land evaluate its anticancer efficiency in mouse models of LLC and 4T1 tumors. AB4/siP-c-L showed a particle size of (180.7 ± 7.3) nm and a ζ-potential of (32.8 ± 1.5) mV, with high drug encapsulation, pH-sensitive release properties, and good stability in serum. AB4/siP-c-L demonstrated prolonged blood circulation and increased tumor accumulation. Elevated cellular uptake was dependent on the targeting ligand cRGD. This combination induced significant tumor inhibition in LLC xenograft tumor-bearing mice by downregulating PD-L1 protein expression and modulating the immunosuppressive microenvironment. Liposomes favored the antitumor T-cell response with long-term memory, without obvious toxicity. A similar tumor growth inhibition was also demonstrated in the 4T1 tumor model. In summary, our results indicate that cRGD-modified and AB4and PD-L1 siRNA-coloaded liposomes have potential as an antitumor preparation, and this approach may lay a foundation for the development of a new targeted drug delivery system.

Lipid–Polymer Hybrid Nanoparticles with Both PD-L1 Knockdown and Mild Photothermal Effect for Tumor Photothermal Immunotherapy

“…Intratumoral administration can be applied only locally and cannot allow nanoparticles to enter the distant tumor and tumor metastatic foci. Many other antitumor studies utilizing siPD-L1 also use intravenous injection. – Therefore, this study used intravenous injection instead of intratumoral administration.…”

“…PD-L1 plays a critical role in the transformation and proliferation of Tregs. PD-L1 can promote the transformation of Foxp3 + Tregs and its immunosuppressive function in vivo . It has been reported that the use of siRNA to downregulate the expression of PD-L1 in tumors is conducive to reducing the Tregs population.…”

“…PD-L1 can promote the transformation of Foxp3 + Tregs and its immunosuppressive function in vivo. 47 It has been reported that the use of siRNA to downregulate the expression of PD-L1 in tumors is conducive to reducing the Tregs population. Foxp3 is an important marker of Tregs.…”

“…Its high expression indicates that Tregs have an inhibitory effect on the antitumor immune response of cytotoxic T cells. 47 Therefore, we analyzed Foxp3 + Tregs in the tumor microenvironment, and the results are shown in Figure 6G,H. The population of Tregs in the tumor microenvironment in the PBS group was the highest, 27%.…”

Development of D-α-Tocopherol polyethylene glycol 1000 succinate fabricated nanostructural lipid carrier of sorafenib tosylate for metastatic colorectal targeting application: Stability, physical characterization, cytotoxicity, and apoptotic studies against SW48 cells PTEN

“…To achieve enhanced lymphatic drug delivery system (LDDS), more advanced fundamental research is going on in the filed of lipid-based nanoparticles, dendrimers, liposomes, polymeric nanoparticles ( 2 ). In more conventional way to deliver medicines through LDDS approach, dermal injection is a promising approach ( 3 , 4 ). However, nanoscale materials are capable of crossing stratum corneum; which is basically a barrier which stops topically applied medicine from getting to where it needs to go.…”