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

Enling Chang,Michael S Valic,Jenny W H Lou,Véronique Rosilio,Jiachuan Bu,Juan Chen,Lili Ding,Miffy H Y Cheng,Gang Zheng

doi:10.1186/s12951-021-00898-1

Abstract

BackgroundPorphyrin-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.ResultsPTX (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.ConclusionPLNE-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

Highlights

Photodynamic therapy (PDT) is a minimally-invasive treatment modality, in which irradiation of photosensitizers that have accumulated in the tumor can produce cytotoxic reactive oxygen species to induce tumor regression
A porphyrin-lipid nanoemulsion was formulated by the self-assembly of porphyrin-lipid around a glyceryl trioctanoate oil core, resulting in a simple, monodisperse, two-component nanoemulsion (PLNEnoPEG) with a hydrodynamic diameter of 120.3 ± 1.1 nm and surface charge of − 2.4 ± 0.3 mV (Fig. 2A and B)
The surface tension of PLNEnoPEG was measured after two weeks storage, on day 15 (D15), and 40 days following the first measurement (D55)

Summary

Introduction

Photodynamic therapy (PDT) is a minimally-invasive treatment modality, in which irradiation of photosensitizers that have accumulated in the tumor can produce cytotoxic reactive oxygen species to induce tumor regression. The combination of PDT and chemotherapy in a single platform may provide a treatment strategy that enables synergistic therapeutic effects, reduces side effects, and minimizes multi-drug resistance [11,12,13,14,15]. PDT enables vascular permeabilization and reduces extravascular barriers, which may enhance the deposition of chemotherapeutic drugs into tumors to improve therapeutic efficacy, while limiting systemic off-target toxicities. 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

Methods

Results

Discussion

Conclusion