yaoyao guo,Manzhen Li,xinxin liu,xi wang,ziqi zhang,dongchun liu,Xiangtao Wang
Nearly all the anti-tumor drugs can benefit greatly from tumor-targeted delivery for improved therapeutic efficacy and reduced toxic side effects. However, the vast majority of tumor-targeting ligands can only target to specific tumor cells highly expressed the corresponding receptors and thus applicable to limited tumor types. Heptadecyanines with medium cyclohexene and medium -Cl atoms, such as IR780 and IR808, have shown an unusual ability to indiscriminately accumulate into virtually all tumor types. In this study, IR808 was conjugated with DSPE-mPEG2000-NH2 and the resultant DSPE-PEG2000-IR808 (DP-IR808) in combination with TPGS, successfully encapsulated paclitaxel (PTX) and immunomodulator R848 into nanoparticles with a small particle size of 150.20 nm, a negative charge of -16.50 mV, rod-like morphology and a PTX loading content of 31.6 %. The obtained DP-IR808@PTX-R848 NPs rapidly accumulated into 4T1 tumors with a tumor/liver fluorescence ratio of 1.71 and a significant photothermal effect and could be directly used for NIR imaging. DP-IR808@PTX-R848 NPs achieved a high tumor inhibition rate of 94%, a mean survival time of > 90 d and a tumor-free survival percentage of 57%. As far as we know, this was the first time that nanoparticles were modified with heptamethylcyanine molecules. Nanoparticles based on DSPE-PEG-IR808, which integrates tumor targeted drug delivery, in vivo infrared imaging and photothermal therapy, is expected to become a versatile drug delivery platform for tumor therapy.
Phototheranostics, a local non-invasive approach that integrates light-based diagnostics and therapeutics, enables precise treatment using nanotheranostic agents with minimal damage to normal tissues. However, ensuring high-efficiency ablation of cancer cells using phototheranostics for one time irradiation is highly challenging. Herein, we designed and synthesized a single-walled carbon nanohorns-based nanotheranostic agent, HA-IR808-SWNHs, by loading IR808, a photosensitizer, conjugated hyaluronic acid (HA) with an amide bond on the surface of single-walled carbon nanohorns (SWNHs) through noncovalent π − π interaction by the sonication method. The HA in HA-IR808-SWNHs improves the water dispersibility of SWNHs and endows SWNHs with targeting capabilities. Importantly, overexpressed endogenous hyaluronidase in cancer cells actively disassembles HA-IR808-SWNHs, forming small HA-IR808 fragments. The fragments exhibit a strong fluorescence signal and can be used to guide programmed photodynamic therapy for sequentially eliminating the residual living cancer cells. The current study confirms that HA-IR808-SWNHs is an endogenous enzyme-responsive nanotheranostic agent that can be employed to precisely track and ablate residual cancer cells in a spatiotemporal manner. The results strengthen the understanding of SWNH functionalization and expand its potential biomedical application, especially in cancer theranostics.
Mesoporous platinum (mPt) nanozyme possessed enzyme-like property of catalase (CAT) and peroxidase (POD), but the insufficient hydrogen peroxide (H 2 O 2 ) concentration severely restricted its application in photodynamic therapy (PDT) and catalytic therapy. Herein, by depositing ultrasmall gold nanoparticles (AuNPs) and modifying photosensitizer IR808, a multifunctional nanozyme (mPt@Au-IR808) was designed to promote PDT/catalytic therapy through cascade enzyme-like reactions of glucose oxidase (GOx) and CAT/POD. In tumor microenvironment, the CAT-like oxygen (O 2 ) generation improved the PDT efficacy, and the POD-like hydroxyl radical (·OH) generation achieved endogenous catalytic therapy. Using the GOx/CAT-like activities and endogenous H 2 O 2 , the yields of singlet oxygen and ·OH were significantly promoted. Furthermore, mPt@Au-IR808 showed higher photothermal conversion efficiency (41.2%) than mPt (36.1%). By combining the photothermal therapy and enhanced PDT/catalytic therapy, the developed mPt@Au-IR808 nanozyme showed excellent anti-tumor efficacy, which will be promising as cascade nanozyme to promote photo/catalytic therapy.
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