Porphyrin-lipid stabilized paclitaxel nanoemulsion for combined photodynamic therapy and chemotherapy

Abstract

Background Porphyrin-lipids are versatile building blocks that enable cancer theranostics and have been applied to create several multimodal nanoparticle platforms, including liposome-like porphysome (aqueous-core), porphyrin nanodroplet (liquefied gas-core), and ultrasmall porphyrin lipoproteins. Here, we used porphyrin-lipid to stabilize the water/oil interface to create porphyrin-lipid nanoemulsions with paclitaxel loaded in the oil core (PLNE-PTX), facilitating combination photodynamic therapy (PDT) and chemotherapy in one platform. Results PTX (3.1 wt%) and porphyrin (18.3 wt%) were loaded efficiently into PLNE-PTX, forming spherical core–shell nanoemulsions with a diameter of 120 nm. PLNE-PTX demonstrated stability in systemic delivery, resulting in high tumor accumulation (~ 5.4 ID %/g) in KB-tumor bearing mice. PLNE-PTX combination therapy inhibited tumor growth (78%) in an additive manner, compared with monotherapy PDT (44%) or chemotherapy (46%) 16 days post-treatment. Furthermore, a fourfold reduced PTX dose (1.8 mg PTX/kg) in PLNE-PTX combination therapy platform demonstrated superior therapeutic efficacy to Taxol at a dose of 7.2 mg PTX/kg, which can reduce side effects. Moreover, the intrinsic fluorescence of PLNE-PTX enabled real-time tracking of nanoparticles to the tumor, which can help inform treatment planning. Conclusion PLNE-PTX combining PDT and chemotherapy in a single platform enables superior anti-tumor effects and holds potential to reduce side effects associated with monotherapy chemotherapy. The inherent imaging modality of PLNE-PTX enables real-time tracking and permits spatial and temporal regulation to improve cancer treatment. Graphic Abstract

Nanomedicine in Clinical Photodynamic Therapy for the Treatment of Brain Tumors

“…According to the nanostructure, nanoparticles can be generally categorized into three types: 1) NPs with mixed hydrophilic and hydrophobic domains, 2) NPs with a core-shell structure, and 3) NPs with a double-layered capsule structure ( Figure 2 ). In this respect, natural polysaccharides such as hyaluronic acid (HA) [ 102 , 103 , 104 , 105 ], chitosan [ 102 , 106 , 107 , 108 ], chitin, heparin [ 95 , 99 , 100 ], and fucoidan [ 84 ] have been utilized as potential photosensitizer carriers due to their biocompatibility and biodegradability. In addition, not only polymers but also hydrophobic small molecule anticancer drugs (such as doxorubicin [ 96 ], docetaxel [ 97 , 107 , 109 , 110 ], paclitaxel [ 85 , 93 , 103 , 111 , 112 ], camptothecin, and quercetin [ 113 , 114 ]) can be grafted onto PS.…”

Graphene quantum dot-porphyrin/phthalocyanine multifunctional hybrid systems: from interfacial dialogue to application

“…71,[152][153][154] These problems can be easily circumvented by constructing a hybrid system of GQDs-Pp/Pc via interface engineering, overcoming the inherent problems associated with porphyrinic compounds and enhancing the efficacy of GQDs for various applications. 131,[155][156][157][158]193 The functionalization of GQDs is an efficient strategy to enhance the basic properties of nanocomposites, resulting in several additional optico-physicochemical properties for wider applications. 1,42,43,85,103,159,160 Currently, porphyrins are applied in optics and medicine, such as nonlinear absorbers or PDT, which increasingly require the use of far-red absorbing dyes.…”

“…71,152–154 These problems can be easily circumvented by constructing a hybrid system of GQDs-Pp/Pc via interface engineering, overcoming the inherent problems associated with porphyrinic compounds and enhancing the efficacy of GQDs for various applications. 131,155–158,193…”

The Combination of Solid-State Chemistry and Medicinal Chemistry as the Basis for the Synthesis of Theranostics Platforms

“…Porphyrin lipids have been used [33] to create several multimodal nanoparticle platforms, including liposome-like porphysomes (water core), porphyrin nanodrops (liquefied gas core), and ultra-small porphyrin lipoproteins. Porphyrin lipids were used to stabilize the water/oil interface to create porphyrin-lipid nanoemulsions with paclitaxel (PTX) loaded into an oil core (PLNE-PTX).…”