Single enzyme loaded nanoparticles for combinational ultrasound-guided focused ultrasound ablation and hypoxia-relieved chemotherapy

Abstract

Constructing nanosystems that synergistically combine therapeutic and diagnostic features is of great interest to the nanomedicine community but also remains a tremendous challenge.Methods: In this work, we report novel catalytic nanoparticles composed of the enzyme catalase, encapsulated in a polymer shell and surface decorated with pH-sensitive poly(ethylene glycol) (PEGylated nCAT). These nanoparticles were used as a promoter for ultrasound (US)-guided focused ultrasound (FUS) ablation and hypoxia alleviation for application in Doxorubicin-based chemotherapy.Results: The PEGylated nCAT produced highly effectively O2 from endogenous H2O2 to ameliorate the hypoxic and therefore poor-acoustic tumor environment. The generated O2 was utilized as 1) a contrast agent for US imaging; 2) strengthening agent for FUS ablation and 3) normoxia inducer to enhance chemotherapeutic efficacy. The PEGylated nCAT exhibited favorable enzyme activity after long-term storage, and after exposure to proteolytic conditions and elevated temperatures. The pH-responsive PEGylation contributed on the one hand to an extended in vivo circulation time over 48 h and on the other hand enabled PEG cleavage in the vicinity of cancer cells to facilitate cellular uptake.Conclusion: The developed PEGylated nCAT can therefore effectively combine US-guided FUS and chemotherapy and can be regarded as a highly promising theranostic platform.

Surface-Charge-Switchable Nanoclusters for Magnetic Resonance Imaging-Guided and Glutathione Depletion-Enhanced Photodynamic Therapy

“…The enzyme activities of catalyzing H 2 O 2 to generate O 2 were determined by recording the decomposition of H 2 O 2 using the UV absorbance of 240 nm. 52 Briefly, the H 2 O 2 solution was diluted with PBS to give an A 240 between 0.52 and 0.55. Native CAT, CM, BM, BMGCC, CM, and CMGCC samples were diluted with PBS to reach a CAT concentration of 50 μg/mL for each sample.…”

Dendrimer-decorated nanogels: Efficient nanocarriers for biodistribution in vivo and chemotherapy of ovarian carcinoma

“…A 3D cross-linked polymer colloids, nanogels (NGs) as nanocarriers have attracted much attention in biomedical applications, including drug/enzyme delivery, images and therapy of tumors, due to their unique properties [ [14] , [15] , [16] ]. All the time we explored various NGs that having the controllable size, deformable softness, highly porous network, excellent biocompatibility and stimuli-responsiveness can be employed as functional nanocarriers for improved tumor theranostics [ [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] ]. In particular, the biocompatible PVCL-based NGs exist a volume phase transition temperature (VPTT) of about 35 °C which is close to body temperature, and high cargo loading capacity along with enhanced tumor accumulation for biomedical purposes [ [26] , [27] , [28] ].…”

The EPR effect and beyond: Strategies to improve tumor targeting and cancer nanomedicine treatment efficacy

“…Such nano-interventions have been combined with other modalities such as chemotherapy, gene therapy and photodynamic therapy to achieve synergistic effects for cancer treatment. Zhu et al report on a pH-sensitive nanomedicine formulation combining an enzyme, focused ultrasound-based tumor ablation and hypoxia alleviation to potentiate doxorubicin-based chemotherapy 32 . Their catalase-loaded nanoparticles were able to increase oxygen levels in tumors by converting H 2 O 2 to O 2 , which improved the effect of ultrasound ablation and reduced tumor hypoxia, and these effects together improved doxorubicin efficacy.…”