Design of a targeted dual drug delivery system for boosting the efficacy of photoimmunotherapy against melanoma proliferation and metastasis.

INTRODUCTION: The combination of a photosensitizer and indoleamine-2,3 dioxygenase (IDO) inhibitor provides a promising photoimmunotherapy (PIT) strategy for melanoma treatment. A dual drug delivery system offers a potential approach for optimizing the inhibitory effects of PIT on melanoma proliferation and metastasis. OBJECTIVE: To develop a dual drug delivery system based on PIT and to study its efficacy in inhibiting melanoma proliferation and metastasis. METHODS: We constructed a multifunctional nano-porphyrin material (P18-APBA-HA) using the photosensitizer-purpurin 18 (P18), hyaluronic acid (HA), and 4-(aminomethyl) phenylboronic acid (APBA). The resulting P18-APBA-HA was inserted into a phospholipid membrane and the IDO inhibitor epacadostat (EPA) was loaded into the internal phase to prepare a dual drug delivery system (Lip\EPA\P18-APBA-HA). Moreover, we also investigated its physicochemical properties, targeting, anti-tumor immunity, and anti-tumor proliferation and metastasis effects. RESULTS: The designed system utilized the pH sensitivity of borate ester to realize an enhanced-targeting strategy to facilitate the drug distribution in tumor lesions and efficient receptor-mediated cellular endocytosis. The intracellular release of EPA from Lip\EPA\P18-APBA-HA was triggered by thermal radiation, thereby inhibiting IDO activity in the tumor microenvironment, and promoting activation of the immune response. Intravenous administration of Lip\EPA\P18-APBA-HA effectively induced anti-tumor immunity by promoting dendritic cell maturation, cytotoxic T cell activation, and regulatory T cell suppression, and regulating cytokine secretion, to inhibit the proliferation of melanoma and lung metastasis. CONCLUSION: The proposed nano-drug delivery system holds promise as offers a promising strategy to enhance the inhibitory effects of the combination of EPA and P18 on melanoma proliferation and metastasis.

Targeted treatment of atherosclerosis with protein-polysaccharide nanoemulsion co-loaded with photosensitiser and upconversion nanoparticles.

Macrophages are the most abundant cell group in atherosclerosis (AS) lesions and play a vital role in all stages of AS progression. Recent research has shown that reactive oxygen species (ROS) generation from photodynamic therapy (PDT) induces macrophage autophagy to improve abnormal lipid metabolism and inflammatory environment. Especially in macrophage-derived foam cells, which has become a potential strategy for the treatment of AS. In this study, we prepared the conjugate (DB) of dextran (DEX) and bovine serum albumin (BSA). The DB was used as the emulsifier to prepare nanoemulsion loaded with upconversion nanoparticles (UCNPs) and chlorin e6 (Ce6) (UCNPs-Ce6@DB). The DEX modified on the surface of the nanoemulsion can recognise and bind to the scavenger receptor class A (SR-A) highly expressed on macrophages and promote the uptake of macrophage-derived foam cells in AS plates through SR-A-mediated endocytosis. In addition, UCNPs-Ce6@DB-mediated PDT enhanced ROS generation and induced autophagy in macrophage-derived foam cells, enhanced the expression of ABCA1, a protein closely related to cholesterol efflux, and inhibited the secretion of pro-inflammatory cytokines. Ultimately, UCNPs-Ce6@DB was shown to inhibit plaque formation in mouse models of AS. In conclusion, UCNPs-Ce6@DB offers a promising treatment for AS.

Fabrication of a protein-dextran conjugates formed oral nanoemulsion and its application to deliver the essential oil from Alpinia zerumbet Fructus.

The injury of vascular endothelial cells caused by high glucose (HG) is one of the driving factors of vascular complications of diabetes. Oral administration is the most common route of administration for the treatment of diabetes and its vascular complications. Essential oil extracts from Chinese medicine possess potential therapeutic effects on vascular endothelial injury. However, low solubility and volatility of essential oils generally result in poor oral absorption. Development of nanocarriers for essential oils is a promising strategy to overcome the physiological barriers of oral absorption. In this study, a nanoemulsion composed of bovine serum albumin (BSA)-dextran sulfate (DS) conjugate and sodium deoxycholate (SD) was constructed. The nanoemulsions were verified with promoted oral absorption and prolonged circulation time. After the primary evaluation of the nanoemulsion, essential oil from Alpinia zerumbet Fructus (EOFAZ)-loaded nanoemulsion (denoted as EOFAZ@BD5/S) was prepared and characterized. Compared to the free EOFAZ, EOFAZ@BD5/S increased the protective effects on HG-induced HUVEC injury in vitro and ameliorative effects on the vascular endothelium disorder and tunica media fibroelastosis in a T2DM mouse model. Collectively, this study provides a nanoemulsion for the oral delivery of essential oils, which holds strong promise in the treatment of diabetes-induced vascular endothelial injury.

Fabrication of a Polysaccharide-Protein/Protein Complex Stabilized Oral Nanoemulsion to Facilitate the Therapeutic Effects of 1,8-Cineole on Atherosclerosis.

Atherosclerosis (AS) is a systemic disease characterized by lipid deposition in the blood vessel wall that urgently requires effective and safe therapeutic drugs for long-term treatment. An essential oil monomer-1,8-cineole (CIN) with ameliorative effects on vascular injuries has considerable potential for preventing the progression of AS because of its antioxidant, anti-inflammation, and cholesterol regulatory effects. However, the high volatility and instability of CIN result in low oral bioavailability and a short half-life, thereby limiting its clinical application. We formulated a nanoemulsion using a polysaccharide-protein/protein complex (dextran-bovine serum albumin/protamine, DEX5k-BSA/PTM) as an emulsifier, with vitamin B12 (VB12) as the ligand to facilitate the transportation across the small intestine. An emulsion preparation method using a microjet followed by ultraviolet irradiation was developed to obtain the CIN-loaded oral nanoemulsion CIN@DEX5k-BSA/PTM/VB12. The nanoemulsion improved the stability of CIN both in vitro and in vivo, prolonged the retention time in the gastrointestinal tract (GIT), and enhanced the permeability across the mucus layer and intestinal epithelial cells to increase oral bioavailability and plaque accumulation of CIN. Validated in an AS mouse model, CIN@DEX5k-BSA/PTM/VB12 achieved prominent therapeutic efficacy combating AS. This study highlights the advantages of DEX5k-BSA/PTM and VB12 in the development of nanoemulsions for CIN and provides a promising oral nanoplatform for the delivery of essential oils.