Design of an Intelligent Sub-50 Nm Nuclear-targeting Nanotheranostic System for Imaging Guided Intranuclear Radiosensitization

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2017 Jul 12

PMID 28694946

Citations 17

Authors

Wenpei Fan

Bo Shen

Wenbo Bu

Xiangpeng Zheng

Qianjun He

Zhaowen Cui

Kuaile Zhao

Shengjian Zhang

Jianlin Shi

Affiliations

Soon will be listed here.

Abstract

Clinically applied chemotherapy and radiotherapy is sometimes not effective due to the limited dose acting on DNA chains resident in the nuclei of cancerous cells. Herein, we develop a new theranostic technique of "intranuclear radiosensitization" aimed at directly damaging the DNA within the nucleus by a remarkable synergetic chemo-/radiotherapeutic effect based on intranuclear chemodrug-sensitized radiation enhancement. To achieve this goal, a sub-50 nm nuclear-targeting rattle-structured upconversion core/mesoporous silica nanotheranostic system was firstly constructed to directly transport the radiosensitizing drug Mitomycin C (MMC) into the nucleus for substantially enhanced synergetic chemo-/radiotherapy and simultaneous magnetic/upconversion luminescent (MR/UCL) bimodal imaging, which can lead to efficient cancer treatment as well as multi-drug resistance circumvention and . We hope the technique of intranuclear radiosensitization along with the design of nuclear-targeting nanotheranostics will contribute greatly to the development of cancer theranostics as well as to the improvement of the overall therapeutic effectiveness.

Citing Articles

Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy.

Liu X, Li M, Woo S Pharmaceutics. 2024; 16(9).

PMID: 39339204 PMC: 11434838. DOI: 10.3390/pharmaceutics16091167.

Nanoradiosensitizers in glioblastoma treatment: recent advances and future perspectives.

Liu M, Li T, Zhao M, Qian C, Wang R, Liu L Nanomedicine (Lond). 2024; 19(26):2229-2249.

PMID: 39311492 PMC: 11487349. DOI: 10.1080/17435889.2024.2395238.

Targeting the organelle for radiosensitization in cancer radiotherapy.

Sun X, Wu L, Du L, Xu W, Han M Asian J Pharm Sci. 2024; 19(2):100903.

PMID: 38590796 PMC: 10999375. DOI: 10.1016/j.ajps.2024.100903.

Co-delivery of doxorubicin and hydroxychloroquine via chitosan/alginate nanoparticles for blocking autophagy and enhancing chemotherapy in breast cancer therapy.

Zhang H, Xue Q, Zhou Z, He N, Li S, Zhao C Front Pharmacol. 2023; 14:1176232.

PMID: 37229260 PMC: 10203398. DOI: 10.3389/fphar.2023.1176232.

Application of nanomedicine in radiotherapy sensitization.

Song X, Sun Z, Li L, Zhou L, Yuan S Front Oncol. 2023; 13:1088878.

PMID: 36874097 PMC: 9977159. DOI: 10.3389/fonc.2023.1088878.

References

Rose P, Bundy B, Watkins E, Thigpen J, Deppe G, Maiman M . Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999; 340(15):1144-53. DOI: 10.1056/NEJM199904153401502. View

Nakae T, Uto Y, Tanaka M, Shibata H, Nakata E, Tominaga M . Design, synthesis, and radiosensitizing activities of sugar-hybrid hypoxic cell radiosensitizers. Bioorg Med Chem. 2007; 16(2):675-82. DOI: 10.1016/j.bmc.2007.10.035. View

Li C, Hou Z, Dai Y, Yang D, Cheng Z, Ma P . A facile fabrication of upconversion luminescent and mesoporous core-shell structured β-NaYF:Yb, Er@mSiO nanocomposite spheres for anti-cancer drug delivery and cell imaging. Biomater Sci. 2020; 1(2):213-223. DOI: 10.1039/c2bm00087c. View

Shen J, Chen G, Ohulchanskyy T, Kesseli S, Buchholz S, Li Z . Tunable near infrared to ultraviolet upconversion luminescence enhancement in (α-NaYF4 :Yb,Tm)/CaF2 core/shell nanoparticles for in situ real-time recorded biocompatible photoactivation. Small. 2013; 9(19):3213-7. DOI: 10.1002/smll.201300234. View

Zhou J, Sun Y, Du X, Xiong L, Hu H, Li F . Dual-modality in vivo imaging using rare-earth nanocrystals with near-infrared to near-infrared (NIR-to-NIR) upconversion luminescence and magnetic resonance properties. Biomaterials. 2010; 31(12):3287-95. DOI: 10.1016/j.biomaterials.2010.01.040. View

Gu Z, Yan L, Tian G, Li S, Chai Z, Zhao Y . Recent advances in design and fabrication of upconversion nanoparticles and their safe theranostic applications. Adv Mater. 2013; 25(28):3758-79. DOI: 10.1002/adma.201301197. View

Grau C, Agarwal J, Jabeen K, Khan A, Abeyakoon S, Hadjieva T . Radiotherapy with or without mitomycin c in the treatment of locally advanced head and neck cancer: results of the IAEA multicentre randomised trial. Radiother Oncol. 2003; 67(1):17-26. DOI: 10.1016/s0167-8140(03)00020-3. View

Duan X, Xiao J, Yin Q, Zhang Z, Yu H, Mao S . Smart pH-sensitive and temporal-controlled polymeric micelles for effective combination therapy of doxorubicin and disulfiram. ACS Nano. 2013; 7(7):5858-69. DOI: 10.1021/nn4010796. View

He Q, Gao Y, Zhang L, Zhang Z, Gao F, Ji X . A pH-responsive mesoporous silica nanoparticles-based multi-drug delivery system for overcoming multi-drug resistance. Biomaterials. 2011; 32(30):7711-20. DOI: 10.1016/j.biomaterials.2011.06.066. View

10.

Zhou J, Liu Z, Li F . Upconversion nanophosphors for small-animal imaging. Chem Soc Rev. 2011; 41(3):1323-49. DOI: 10.1039/c1cs15187h. View

11.

Liu J, Bu W, Pan L, Shi J . NIR-triggered anticancer drug delivery by upconverting nanoparticles with integrated azobenzene-modified mesoporous silica. Angew Chem Int Ed Engl. 2013; 52(16):4375-9. DOI: 10.1002/anie.201300183. View

12.

Wunderbaldinger P, Josephson L, Weissleder R . Tat peptide directs enhanced clearance and hepatic permeability of magnetic nanoparticles. Bioconjug Chem. 2002; 13(2):264-8. DOI: 10.1021/bc015563u. View

13.

Kennedy K, Rockwell S, Sartorelli A . Preferential activation of mitomycin C to cytotoxic metabolites by hypoxic tumor cells. Cancer Res. 1980; 40(7):2356-60. View

14.

Liu J, Bu W, Zhang S, Chen F, Xing H, Pan L . Controlled synthesis of uniform and monodisperse upconversion core/mesoporous silica shell nanocomposites for bimodal imaging. Chemistry. 2012; 18(8):2335-41. DOI: 10.1002/chem.201102599. View

15.

Idris N, Gnanasammandhan M, Zhang J, Ho P, Mahendran R, Zhang Y . In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers. Nat Med. 2012; 18(10):1580-5. DOI: 10.1038/nm.2933. View

16.

Hogle W . The state of the art in radiation therapy. Semin Oncol Nurs. 2006; 22(4):212-20. DOI: 10.1016/j.soncn.2006.07.004. View

17.

Gao J, Feng S, Guo Y . Nanomedicine against multidrug resistance in cancer treatment. Nanomedicine (Lond). 2012; 7(4):465-8. DOI: 10.2217/nnm.12.11. View

18.

Park Y, Kim H, Kim J, Moon K, Yoo B, Lee K . Theranostic probe based on lanthanide-doped nanoparticles for simultaneous in vivo dual-modal imaging and photodynamic therapy. Adv Mater. 2012; 24(42):5755-61. DOI: 10.1002/adma.201202433. View

19.

Shen J, He Q, Gao Y, Shi J, Li Y . Mesoporous silica nanoparticles loading doxorubicin reverse multidrug resistance: performance and mechanism. Nanoscale. 2011; 3(10):4314-22. DOI: 10.1039/c1nr10580a. View

20.

Tomasz M . Mitomycin C: small, fast and deadly (but very selective). Chem Biol. 1995; 2(9):575-9. DOI: 10.1016/1074-5521(95)90120-5. View