An Oxygen Self-sufficient Fluorinated Nanoplatform for Relieved Tumor Hypoxia and Enhanced Photodynamic Therapy of Cancers

Abstract

The efficacy of photodynamic therapy (PDT) in the solid tumor is hampered by many challenges, including its oxygen self-consuming nature, insufficient oxygen levels within the hypoxic tumor microenvironment, and limited penetration of photosensitizers within tumors. Herein, we develop the IR780@O2-SFNs/iRGD as an oxygen self-sufficient and tumor-penetrating nanoplatform, which consists of IR780-loaded pH-sensitive fluorocarbon-functionalized nanoparticles (SFNs) and iRGD as a tumor targeting peptide that can penetrate deeper within the tumor. Because of the high oxygen affinity and outstanding permeability of the obtained nanoplatform, oxygen and IR780 which are encapsulated in the same core can play their roles to the utmost, resulting in remarkably accelerated singlet oxygen production, as demonstrated in vitro by the 3D multicellular spheroids and in vivo by tumor tissues. More interestingly, a single-dose intravenous administration of IR780@O2-SFNs/iRGD into mice bearing orthotopic breast cancer could selectively accumulate at the tumor site, highly alleviate the tumor hypoxia, significantly inhibit the primary tumor growth, and reduce the lung and liver metastasis, enabling the improved photodynamic therapeutic performance. Thus, this work paves an effective way to improve PDT efficacy through increasing tumor oxygenation and selective delivery of photosensitizers to the deep and hypoxic tumor.

Fighting Hypoxia to Improve PDT

“…Ma et al [65] prepared NPs with fluorocarbon chains and IR780 PS in the core and iRGD peptides on the shell (diameter 80 nm). 1…”

Fluorinated peptide biomaterials

“…[127][128] tumor growth over the course of 12 days. [129] MRI has also seen improvements in imaging resolution through the use of 19 F-MR contrast agents, which take advantage of limited fluorine content in biologic tissues to improve signaling contrast over the typically used 1 H nuclei abundantly found in biological systems. [130] Accordingly, nanoscale 19 F-fluoropeptides have been designed to switch 19 F-MRI signal "off" and "on" via stimuli-responsive assembly controlled by pH, [67] temperature, [131] and calcium, [41] or enzyme concentration.…”

“…developed peptide‐dendron 100 nm nanoparticles that assemble to form a fluorous core suitable for co‐loading of molecular oxygen and the photosensitizer IR780 (IR780@O 2 ‐SFNs). [ 129 ] IR780@O 2 ‐SFNs demonstrated superior oxygen loading and sustained release in deoxygenated environments compared to hydrocarbon functionalized analogs. The fluorinated constructs were also able to diffuse into the hypoxic core of ex vivo 4T1 spheroid models and accumulated into 4T1‐xenografts in tumor‐bearing mice in vivo to improve tissue oxygenation.…”

“…NIR irradiation of tumors in IR780@O 2 ‐SFN treated mice resulted in a nearly complete cessation of tumor growth over the course of 12 days. [ 129 ]…”

Anti-Cancer Nanomedicines: A Revolution of Tumor Immunotherapy

“…Perfluorocarbon is a safe O 2 carrier that has been already demonstrated in clinic, and the encapsulation of perfluorocarbon with albumin enhanced its accumulation in the tumor site and rapidly released the oxygen that was physically dissolved ( 69 ). Fluorocarbon-functionalized nanoparticles enhanced the effects of both photodynamic therapy (PDT) ( 70 ) and oxygen-sensitive anti-tumor drugs ( 71 ) by increasing tumor oxygenation. Besides, perfluorocarbons have entered clinical trials for ischemia and imaging theranostic strategies to ensure that the simple O 2 transport system can be rapidly and easily transformed into clinical applications.…”