Purpose
Cell membrane-camouflaged nanoparticles (NPs) are drawing increasing attention because their surfaces acquire some characteristics of the cell membranes, making them a unique class of biomimetic materials for diverse applications. Modification of cell membrane or combination of different types of membranes can enhance their functionality.
Methods
We prepared platelet and tumor cell membrane camouflaged β-mangostin-loaded NPs, which were synthesized with platelet–C6 hybrid biomimetic coating, poly(lactic-co-glycolic acid), and β-mangostin (β-PCNPs). Then, we evaluated their targeting ability and anticancer activity against glioma in vitro and in vivo.
Results
Biomimetic coating enhanced active drug targeting and immune escape properties of nanocarrier in C6 and THP-1 cells, respectively, which improved their cytotoxicity. β-PCNPs were characterized to study the inherent properties of both source cells. Compared with bare β-NPs, β-PCNPs exhibited high tumor-targeting capability and induced apoptosis of C6 cells in vitro. Similarly, intravenous administration of drug through β-PCNPs resulted in enhanced tumor-targeting and exhibited excellent rate of inhibition of glioma tumor growth in mice. Moreover, the blood circulation time of drug in mice in the β-PCNP group was markedly prolonged and these mice exhibited better outcome than those in the β-NP group.
Conclusion
These results provide a new strategy of utilizing PCNPs as carriers for drug delivery, which improves the targeting efficiency and therapeutic efficacy of chemotherapeutic agents for glioma therapy.
Although enormous success has been obtained for dendritic cells (DCs)‐mediated antigen‐specific T cells anticancer immunotherapy in the clinic, it still faces major challenging problems: insufficient DCs in tumor tissue and low response rate for tumor cells lacking antigen expression, especially in low immunogenic tumors such as pancreatic cancer. Here, these challenges are tackled through tumor microenvironment responsive nanogels with prominent tumor‐targeting capability by Panc02 cell membranes coating and inhibition of tumor‐derived prostaglandin E2 (PGE2), aimed at improving natural killer (NK) cells activation and inducing activated NK cells‐dependent DCs recruitment. The engineered nanogels can on‐demand release acetaminophen to inhibit PGE2 secretion, thus promoting the activity of NK cells for non‐antigen‐specific tumor elimination. Furthermore, activated NK cells can secrete chemokines as CC motif chemokine ligand 5 and X‐C motif chemokine ligand 1 to recruit immature DCs, and then promote DCs maturation and induce antigen‐dependent CD8+ T cells proliferation for enhancing antigen‐specific immunotherapy. Notably, these responsive nanogels show excellent therapeutic effect on Panc02 pancreatic tumor growth and postsurgical recurrence, especially combination of the programmed cell death‐ligand 1 checkpoint‐blockade immunotherapy. Therefore, this study provides a simple strategy for enhancing low immunogenic tumors immunotherapy through an antigen‐independent way and antigen‐dependent way synergetically.
Nanocarriers have shown great advantages in increasing the efficiency of drug delivery and reducing the side effects. However, the lack of targeting and on-demand drug release will seriously limit their...
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