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PH-responsive perylenediimide nanoparticles for cancer trimodality imaging and photothermal therapy.

ABSTRACT: Organic chromophores have been well developed for multimodality imaging-guided photothermal therapy (PTT) due to their outstanding optical properties and excellent designability. However, the theranostic efficiencies of most currently available organic chromophores are restricted intrinsically, owing to their poor photostability or complex synthesis procedures. These drawbacks not only increase their cost of synthesis, but also cause side effects in PTT.Method: We presented a facile strategy for constructing a near-infrared (NIR)-absorbing perylenediimide structured with pH-responsive piperazine ring at the bay region. The chromophore was conjugated with carboxyl-end-capped PEG as side chains that can self-assemble into nanoparticles (NPs) in aqueous solution. The NIR optical properties and photothermal conversation ability of PPDI-NPs were investigated. We then studied the imaging-guided PTT of PPDI-NPs under NIR light illumination in 4T1 cells and mice respectively.Results: The excellent photostable PPDI-NPs had near-infrared fluorescence (NIRF) emission and high photothermal conversion efficiency in acidic microenvironment. Importantly, PPDI-NPs can be utilized for the precise detection of tumors by NIRF/photoacoustic/thermal trimodality imaging. Efficient PTT of PPDI-NPs was applied in vitro and in vivo with high biosafety.Conclusion: In summary, we developed pH-responsive perylenediimide nanoparticles as multifunctional phototheranostic agent with high stability and simple synthesis procedures. This study offers a promising organic chromophore for developing phototheranostics in cancer therapy.

SUBMITTER: Li J

PROVIDER: S-EPMC6929613 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Project description:Photodynamic therapy (PDT) and photothermal therapy (PTT) have garnered considerable interest as non-invasive cancer treatment modalities. However, these approaches remain limited by low solubility, poor stability and inefficient targeting of many common photosensitizers (PSs) and photothermal agents (PTAs). To overcome these limitations, we have designed biocompatible and biodegradable tumor-targeted upconversion nanospheres with imaging capabilities. The multifunctional nanospheres consist of a sodium yttrium fluoride core doped with lanthanides (ytterbium, erbium and gadolinium) and bismuth selenide (NaYF 4 :Yb/Er/Gd,Bi 2 Se 3 ) within a mesoporous silica shell that encapsulates a PS, Chlorin e6 (Ce6), in its pores. NaYF 4 :Yb/Er converts deeply penetrating near-infrared (NIR) light to visible light, which excites the Ce6 to generate cytotoxic reactive oxygen species (ROS), while the PTA Bi 2 Se 3 efficiently converts absorbed NIR light to heat. Additionally, Gd enables magnetic resonance imaging (MRI) of the nanospheres. The mesoporous silica shell is coated with lipid/polyethylene glycol (DPPC/cholesterol/DSPE-PEG) to ensure retention of the encapsulated Ce6 and minimize interactions with serum proteins and macrophages that impede tumor targeting. Finally, the coat is functionalized with the acidity-triggered rational membrane (ATRAM) peptide, which promotes specific and efficient internalization into cancer cells within the mildly acidic tumor microenvironment. Following uptake by cancer cells in vitro , NIR laser irradiation of the nanospheres caused substantial cytotoxicity due to ROS production and hyperthermia. The nanospheres facilitated tumor MRI and thermal imaging, and exhibited potent NIR laser light-induced antitumor effects in vivo via combined PDT and PTT, with no observable toxicity to healthy tissue, thereby substantially prolonging survival. Our results demonstrate that the ATRAM-functionalized, lipid/PEG-coated upconversion mesoporous silica nanospheres (ALUMSNs) offer multimodal diagnostic imaging and targeted combinatorial cancer therapy.

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PH-responsive perylenediimide nanoparticles for cancer trimodality imaging and photothermal therapy.

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