Light‐Triggered Efficient Sequential Drug Delivery of Biomimetic Nanosystem for Multimodal Chemo‐, Antiangiogenic, and Anti‐MDSC Therapy in Melanoma

Abstract

In view of the multiple pathological hallmarks of tumors, nanosystems for the sequential delivery of various drugs whose targets are separately located inside and outside tumor cells are desired for improved cancer therapy. However, current sequential delivery is mainly achieved through enzyme‐ or acid‐dependent degradation of the nanocarrier, which would be influenced by the heterogeneous tumor microenvironment, and unloading efficiency of the drug acting on the target outside tumor cells is usually unsatisfactory. Here, a light‐triggered sequential delivery strategy based on a liposomal formulation of doxorubicin (DOX)‐loaded small‐sized polymeric nanoparticles (DOX‐NP) and free sunitinib in the aqueous cavity, is developed. The liposomal membrane is doped with photosensitizer porphyrin–phospholipid (PoP) and hybridized with red blood cell membrane to confer biomimetic features. Near‐infrared light‐induced membrane permeabilization triggers the “ultrafast” and “thorough” release of sunitinib (100% release in 5 min) for antiangiogenic therapy and also myeloid‐derived suppressor cell (MDSC) inhibition to reverse the immunosuppressive tumor environment. Subsequently, the small‐sized DOX‐NP liberated from the liposomes is more easily uptaken by tumor cells for improved immunogenic chemotherapy. RNA sequencing and immune‐related assay indicates therapeutic immune enhancement. This light‐triggered sequential delivery strategy demonstrates the potency in cancer multimodal therapy against multiple targets in different spatial positions in tumor microenvironment.

A biomimetic nanoplatform for customized photothermal therapy of HNSCC evaluated on patient-derived xenograft models

“…1,2 In the case of superficial tumors such as head and neck squamous cell carcinoma (HNSCC), near-infrared (NIR) light responsive PTT is preferable due to effective photo penetration. [3][4][5] Besides direct damage to cancer cells, PTT has also been shown to promote immunogenic cell death (ICD), a process that causes cancer cells to release tumor-associated antigens, which further trigger the anti-tumor immune response, 6,7 generating the cytotoxic T lymphocytes (CTLs) to eliminate residual tumor cells and inhibit its metastasis. 8 Until now, many PTT studies of oncotherapy based on various photothermal agents (PTAs) have been reported.…”

Recent advances in developing active targeting and multi-functional drug delivery systems via bioorthogonal chemistry

“…Constructing biomimetic DDSs by bioorthogonal chemistry Biomimetic techniques to enable precise drug delivery has become a research focus. [188][189][190][191] The use of natural cell membranes to cover nanoparticles avoids immune system clearance while keeping innate targeting capabilities. The majority of the targeting effects of cell membrane-based biomimetic DDSs are mediated by cytokines or chemokines.…”

Precise Design Strategies of Nanotechnologies for Controlled Drug Delivery

“…Then, the other drug, along with the nanocarrier, is internalized into cells for the intracellular target treatment [ 73 ]. As shown in Figure 4 C, Lai and co-workers [ 71 ] proposed a sequential delivery strategy which mainly relies on a light-responsive liposomes encapsulated with sunitinib [ 74 ] (antiangiogenic inhibitor for multiple cancers).…”