Perfluorohexane-Loaded Polymeric Nanovesicles with Oxygen Supply for Enhanced Sonodynamic Therapy

Abstract

Sonodynamic therapy (SDT), as a new method of non-invasive tumor treatment developed from photodynamic therapy (PDT), can overcome the disadvantage of poor laser penetration while retaining the function of PDT. However, the lack of efficient sonosensitizer accumulation and the hypoxic environment in tumor sites limited the therapeutic efficacy of SDT. Here, we constructed a highly efficient liquid fluorocarbon-encapsulated polymeric nanovesicle for enhanced sonodynamic efficacy as well as tumor hypoxia relief. This multifunctional nanovesicle was constructed by fluorinated cationic polymer C9F17-PAsp­(DET) with PEG-conjugated protoporphyrin IX (PEG-PpIX) modification, which could yield the simultaneous loading of perfluorohexane (PFH) and oxygen. We found that the PAsp­(DET)-PpIX-PEG@PFH nanovesicles could not only generate the reactive oxygen species (ROS) under ultrasound irradiation after intravenous (i.v.) injection but also could generate and prolong the ROS under nanovesicle preparation by ultrasonication in vitro, so-called the ″exogenous ROS”, which might result in enhanced cytotoxicity in tumor tissue. Furthermore, oxygen-loaded PAsp­(DET)-PpIX-PEG nanovesicles could not only reduce therapeutic resistance by relieving tumor hypoxia but also increase ROS production for enhanced sonodynamic therapy. An in vivo study revealed that the nanovesicles could accumulate in the tumor site after i.v. injection and achieved remarkable tumor growth inhibition in both with and without preloaded oxygen groups, which indicated that the nanovesicle system could efficiently achieve oxygen loading during in vivo circulation and provide a better solution for SDT application.

Reactive Oxygen Species‐Regulating Strategies Based on Nanomaterials for Disease Treatment

“…Fortunately, some nanoplatforms that can promote O 2 release by harvesting exogenous stimuli have been fabricated, such as albumin‐stabilized PFC nanodroplets under low‐frequency ultrasound (US) for PDT and RT, [ 153 ] PFC‐loaded Bi 2 Se 3 NPs with near‐infrared (NIR) irradiation for RT, [ 154 ] and polymer‐based PFC nanovesicles in response to US for SDT. [ 155 ]…”

Nanosonosensitizers With Ultrasound-Induced Reactive Oxygen Species Generation for Cancer Sonodynamic Immunotherapy

“…Recent development of nanosonosensitizers with US-induced ROS generation to combine SDT with immunotherapy for cancer treatment has been summarized. Although the efficacies of SDT are often limited by a hypoxic tumor microenvironment, different strategies have been adopted to address this issue, such as the production of molecular oxygen ( Zhang Y. et al, 2020 ), supplement of oxygen ( Zeng et al, 2020 ), and depletion of GSH ( Dong et al, 2020 ). In addition to direct ablation of tumors, SDT can induce ICD of tumor cells, thus promoting the activation of immune responses.…”

Recent Advances in Nanomaterial‐Assisted Combinational Sonodynamic Cancer Therapy

“…Moreover, polymeric nanovesicles and erythromembrane‐coated Prussian blue nanoparticles were both used to encapsulate the liquid FC for O 2 enhanced SDT cancer therapeutics. [ 98 ] Apart from the direct O 2 delivery strategies, the decomposition of endogenous H 2 O 2 with catalysts to generate O 2 has also received much attention. Catalyst‐based enzymes are usually divided into natural enzymes and nanozymes.…”