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Polyethylenimine-based theranostic nanoplatform for glioma-targeting single-photon emission computed tomography imaging and anticancer drug delivery

ABSTRACT: Background Glioma is the deadliest brain cancer in adults because the blood–brain-barrier (BBB) prevents the vast majority of therapeutic drugs from entering into the central nervous system. The development of BBB-penetrating drug delivery systems for glioma therapy still remains a great challenge. In this study, we aimed to design and develop a theranostic nanocomplex with enhanced BBB penetrability and tumor-targeting efficiency for glioma single-photon emission computed tomography (SPECT) imaging and anticancer drug delivery. Results This multifunctional nanocomplex was manufactured using branched polyethylenimine (PEI) as a template to sequentially conjugate with methoxypolyethylene glycol (mPEG), glioma-targeting peptide chlorotoxin (CTX), and diethylenetriaminepentaacetic acid (DTPA) for 99mTc radiolabeling on the surface of PEI. After the acetylation of the remaining PEI surface amines using acetic anhydride (Ac2O), the CTX-modified PEI (mPEI-CTX) was utilized as a carrier to load chemotherapeutic drug doxorubicin (DOX) in its interior cavity. The formed mPEI-CTX/DOX complex had excellent water dispersibility and released DOX in a sustainable and pH-dependent manner; furthermore, it showed targeting specificity and therapeutic effect of DOX toward glioma cells in vitro and in vivo (a subcutaneous tumor mouse model). Owing to the unique biological properties of CTX, the mPEI-CTX/DOX complex was able to cross the BBB and accumulate at the tumor site in an orthotopic rat glioma model. In addition, after efficient radiolabeling of PEI with 99mTc via DTPA, the 99mTc-labeled complex could help to visualize the drug accumulation in tumors of glioma-bearing mice and the drug delivery into the brains of rats through SPECT imaging. Conclusions These results indicate the potential of the developed PEI-based nanocomplex in facilitating glioma-targeting SPECT imaging and chemotherapy.

SUBMITTER: Zhao L

PROVIDER: S-EPMC7557081 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:We present the attenuated spline reconstruction technique (aSRT) which provides an innovative algorithm for single photon emission computed tomography (SPECT) image reconstruction. aSRT is based on an analytic formula of the inverse attenuated Radon transform. It involves the computation of the Hilbert transforms of the linear attenuation function and of two sinusoidal functions of the so-called attenuated sinogram These computations are achieved by employing the attenuation information provided by computed tomography (CT) scans and by utilizing custom-made cubic spline interpolation. The purpose of this work is: (i) to present the mathematics of aSRT, (ii) to reconstruct simulated and real SPECT/CT data using aSRT and (iii) to evaluate aSRT by comparing it to filtered backprojection (FBP) and to ordered subsets expectation minimization (OSEM) reconstruction algorithms. Simulation studies were performed by using an image quality phantom and an appropriate attenuation map. Reconstructed images were generated for 45, 90 and 180 views over 360 degrees with 20 realizations and involved Poisson noise of three different levels (NL), namely 100% (NL1), 50% (NL2) and 10% (NL3) of the total counts, respectively. Moreover, real attenuated SPECT sinograms were reconstructed from a real study of a Jaszczak phantom, as well as from a real clinical myocardial SPECT/CT study. Comparisons between aSRT, FBP and OSEM reconstructions were performed using contrast, bias and image roughness. The results suggest that aSRT can efficiently produce accurate attenuation-corrected reconstructions for simulated and real phantoms, as well as for clinical data. In particular, in the case of the clinical myocardial study, aSRT produced reconstructions with higher cold contrast than both FBP and OSEM. aSRT, by incorporating the attenuation correction within itself, may provide an improved alternative to FBP. This is particularly promising for 'cold' regions as those occurring in myocardial ischaemia.

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Polyethylenimine-based theranostic nanoplatform for glioma-targeting single-photon emission computed tomography imaging and anticancer drug delivery

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