Dataset Information

A "Missile-Detonation" Strategy to Precisely Supply and Efficiently Amplify Cerenkov Radiation Energy for Cancer Theranostics.

ABSTRACT: Cerenkov radiation (CR) from radionuclides can act as a built-in light source for cancer theranostics, opening a new horizon in biomedical applications. However, considerably low tumor-targeting efficiency of existing radionuclides and radionuclide-based nanomedicines limits the efficacy of CR-induced theranostics (CRIT). It remains a challenge to precisely and efficiently supply CR energy to the tumor site. Here, a "missile-detonation" strategy is reported, in which a high dose of p-SCN-Bn-deferoxamine-porphyrin-PEG nanocomplex (Df-PPN) is first adminstered as a CR energy receiver/missile to passively target to tumor, and then a low dose of the ⁸⁹ Zr-labeled Df-PPN is administrated as a CR energy donor/detonator, which can be visualized and quantified by Cerenkov energy transfer imaging, positron-emission tomography, and fluorescence imaging. Based on homologous properties, the colocalization of Df-PPN and ⁸⁹ Zr-Df-PPN in the tumor site is maximized and efficient CR energy transfer is enabled, which maximizes the tumor-targeted CRIT efficacy in an optimal spatiotemporal setting while also reducing adverse off-target effects from CRIT. This precise and efficient CRIT strategy causes significant tumor vascular damage and inhibited tumor growth.

SUBMITTER: Yu B

PROVIDER: S-EPMC6928399 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A "Missile-Detonation" Strategy to Precisely Supply and Efficiently Amplify Cerenkov Radiation Energy for Cancer Theranostics.

Yu Bo B Ni Dalong D Rosenkrans Zachary T ZT Barnhart Todd E TE Wei Hao H Ferreira Carolina A CA Lan Xiaoli X Engle Jonathan W JW He Qianjun Q Yu Faquan F Cai Weibo W

Advanced materials (Deerfield Beach, Fla.) 20191111 52

Cerenkov radiation (CR) from radionuclides can act as a built-in light source for cancer theranostics, opening a new horizon in biomedical applications. However, considerably low tumor-targeting efficiency of existing radionuclides and radionuclide-based nanomedicines limits the efficacy of CR-induced theranostics (CRIT). It remains a challenge to precisely and efficiently supply CR energy to the tumor site. Here, a "missile-detonation" strategy is reported, in which a high dose of p-SCN-Bn-defe ...[more]

PMID: 31709622

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Project description:Background We have developed and validated a set of complementary retroviruses that creates a wide range of nested chromosomal deletions. When applied to mouse ES cells, this retrovirus-based method generated deletions ranging from 6 kb to 23 Mb (average 2.9 Mb), with an efficiency of 64% for drugs-selected clones. Importantly, several of engineered ES cell clones, mostly those with large deletions, showed major alteration in cell fate. The set of complementary replication-defective retroviruses exploited the Cre-loxP recombination system and reconstitution of a functional neomycin cassette for selection of recombination events. The first loxP sequenced was delivered using the anchor virus A1. The integration was selected on puromycin. ES cell clones containing one copy of the virus A1 were isolated and expanded (primary clones). A second loxP was introduced by retroviral gene transfer using the saturation virus S1, selected on hygromycin (secondary clones). The transient expression of the recombinase Cre in secondary clones allowed the recombination between the loxP sites and the functional reconstitution of a split neomycin expression cassette. Neomycin resistant clones (tertiary clones) were isolated and expanded. Chromosomal deletions are expected to have occurred in neomycin resistant clones that have lost both puromycin and hygromycin resistance genes. In addition, other chromosomal rearrangements (e.g., inversions, translocations, etc.) are achievable using this system. Aim Inverse-PCR, array-based comparative genomic hybridization (aCGH) and spectral karyotyping were employed to confirm deletions (or other Cre-induced rearrangements) in several tertiary clones and to assess the genomic integrity of the ES cells altered. Conclusions aCGH conclusions are summarized together with complementary results from inverse-PCR and spectral karyotyping in 3 tables: Table 1: Summary of the virus A1 integration Table 2: Characteristics of independent deletions confirmed by IPCR-aCGH Table 3: Confirmed or suspected recombination events in trans Notes for Table 2: Mapping and deletion analyses were done using the UCSC Genome Browser (NCBI mouse Build 33). {a} Tertiary clones are labeled according to their family number (same integration of virus A1), followed by a specific id number. If more than one clone presented a redundant rearrangement within the same group infected with virus S1, only one is reported for clarity. {b} Anomaly that was not present in the primary clone from which the tertiary clone was derived, as determined by aCGH or SKY. ( -), no anomaly; (+), additional anomaly. {c} The deletion is not observed, in agreement with the resolution of aCGH. {d} Normal except for the loss of chromosome Y. {e} Amplification of chromosome 1. {f} Amplification of chromosome 8. {g} Many chromosomes were lost according to SKY. {h} Amplification on chromosome 14. Id, identification; kb, kilobase pairs; no., number; aCGH, array-based comparative genomic hybridization; SKY, spectral karyotyping; I-PCR, inverse-PCR; n.d., not determined. Keywords: comparative genomic hybridization

Dataset Information

A "Missile-Detonation" Strategy to Precisely Supply and Efficiently Amplify Cerenkov Radiation Energy for Cancer Theranostics.

Publications

A "Missile-Detonation" Strategy to Precisely Supply and Efficiently Amplify Cerenkov Radiation Energy for Cancer Theranostics.

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